Information on whether the         a polymorph that is the
     patent is a re-issued patent of a          same active ingredient
     patent submitted previously for            that is described in the
     listing for the NDA or supplement.         pending NDA or
                                                supplement, and, if so,
                                                has test data described
                                                in Sec.   314.53(b)(2).
                                                Information on
                                                whether the drug
                                                substance patent claims
                                                only a polymorph that is
                                                the same active
                                                ingredient that is
                                                described in the pending
                                                NDA or supplement, and,
                                                if so, has test data
                                                described in Sec.
                                                314.53(b)(2).
Method-of-Use Patents (Sec.                 Method-of-Use Patents (Sec.
 314.53(c)(2)(i)(O) and (c)(2)(ii)(P))        314.53(c)(2)(i)(O) and
                                             (c)(2)(ii)(P))
The required information and verification   The required information and
 in Sec.   314.53(c)(2)(i) and (c)(2)(ii)    verification in Sec.
 includes:                                   314.53(c)(2)(i) and
                                             (c)(2)(ii) includes:
     Information on each method-of-     Information on
     use patent including the following:        each method-of-use
                                                patent including the
                                                following:
        (2) Identification of the specific       (2) Identification of
         section of the proposed labeling         the specific
         for the drug product that                section(s) of the
         corresponds to the method of use         proposed labeling for
         claimed by the patent submitted          the drug product that
        (3) The description of the                corresponds to the
         patented method of use as                method of use claimed
         required for publication.                by the patent
                                                  submitted (if the
                                                  scope of the method-of-
                                                  use claim(s) of the
                                                  patent does not cover
                                                  every use of the drug,
                                                  the applicant must
                                                  identify only the
                                                  specific portion(s) of
                                                  the indication or
                                                  other condition of use
                                                  claimed by the
                                                  patent);
                                                 (3) The description of
                                                  the patented method of
                                                  use as required for
                                                  publication (which
                                                  must contain adequate
                                                  information to assist
                                                  505(b)(2) and ANDA
                                                  applicants in
                                                  determining whether a
                                                  listed method-of-use
                                                  patent claims a use
                                                  for which the
                                                  505(b)(2) or ANDA
                                                  applicant is not
                                                  seeking approval).
[No corresponding regulation]               Exceptions to Required
                                             Submission of Patent
                                             Information (Sec.
                                             314.53(c)(2)(i)(S) and
                                             314.53(c)(2)(ii)(T))
                                             If the applicant
                                             submits information for a
                                             patent that claims the drug
                                             substance (active
                                             ingredient) and meets the
                                             requirements for listing on
                                             that basis, then the
                                             applicant is not required
                                             to provide information on
                                             whether that patent also
                                             claims the drug product
                                             (composition/formulation).
                                             If the applicant
                                             submits information for a
                                             patent that claims the drug
                                             product (composition/
                                             formulation) and meets the
                                             requirements for listing on
                                             that basis, then the
                                             applicant is not required
                                             to provide information on
                                             whether that patent also
                                             claims the drug substance
                                             (active ingredient).

                                             However, an
                                             applicant that submits
                                             information for a method-of-
                                             use patent must also submit
                                             information regarding
                                             whether that patent also
                                             claims either the drug
                                             substance or the drug
                                             product.
------------------------------------------------------------------------
\1\ These highlights describe important proposed revisions to our
  regulations, but should not be relied upon in place of the proposed
  regulation.

    II.B.1.a. Drug substance (active ingredient) and drug product
(formulation or composition) patents. We are proposing to revise Sec.
314.53(c)(1) to clarify that FDA accepts patent information submitted
on Form FDA 3542a or 3542, as appropriate, as long as the form contains
the information required in Sec.  314.53(c). The statement in our
current regulations that FDA ``will not accept the patent information
unless it is complete . . .'' has generated confusion in some cases,
particularly where a portion of the specific information requested in a
section on FDA Form FDA 3542a or 3542 was not applicable to the patent
for which the form was submitted. By proposing to revise Sec.
314.53(c)(1) to state that we will not accept the patent information
unless it ``contains the information required in paragraph (c)(2) of
this section,'' we are clarifying that FDA will accept a submission of
patent information on Form FDA 3542a or 3542, as appropriate, that
omits patent information requested on the form where that omission is
permitted under an exception in Sec.  314.53(c)(2).
    We are proposing to add Sec.  314.53(c)(2)(i)(S) and (c)(2)(ii)(T)
to describe exceptions to the required submission of patent
information. Proposed Sec.  314.53(c)(2)(i)(S)(1) and (c)(2)(ii)(T)(1)
state that if a patent claims the drug substance that is the active
ingredient in the drug product for which approval is sought or has been
granted, respectively, and is eligible for listing in the Orange Book,
it is not necessary for an applicant to provide information on whether
the patent also claims the drug product. Similarly, we are proposing to
add Sec.  314.53(c)(2)(i)(S)(2) and (c)(2)(ii)(T)(2) to provide that if
a patent claims the drug product for which approval is sought or has
been granted, respectively, and is eligible for listing in the Orange
Book, it is not necessary for an applicant to provide information on
whether the patent also claims the drug substance that is the active
ingredient in the drug product. These proposed revisions to our
regulations provide that an applicant need only satisfy the
requirements for patent listing set forth in section 505(b)(1) and
(c)(2) of the FD&C Act and, subject to Sec.  314.53(c)(2)(i)(O)(3) and
(c)(2)(ii)(P)(4), discussed in this section of the document, need not
identify each basis on which the patent claims the drug. The
designation of a patent as claiming the drug substance and/or drug
product for purposes of listing in the Orange Book is not intended to
define the scope of the patent claims that an NDA holder or patent
owner may assert against a 505(b)(2) or ANDA applicant based on a
listed patent.
    Whether or not the applicant provides information stating that the
patent claims the drug substance or the drug product, an applicant must
submit information regarding whether the patent claims one or more
methods of using the drug product for which approval is sought or has
been granted (method-of-use patent). We are proposing to add Sec.
314.53(c)(2)(i)(O)(3) and (c)(2)(ii)(P)(4) to confirm that the proposed
exceptions to required submission of patent information do not alter
the requirements for submission of method-of-use patent information.
The information regarding method-of-use patents is required for
implementation of the patent certification and statement provisions of
the FD&C Act. Section 505(b)(2)(B) and (j)(2)(A)(viii) of the FD&C Act
provide that a 505(b)(2) and ANDA applicant, respectively, may submit a
statement for a method-of-use patent which does not claim a use for
which the applicant is seeking approval, instead of a patent
certification under section 505(b)(2)(A)(iii) or 505(j)(2)(A)(vii)(III)
of the FD&C Act (paragraph III certification) or a paragraph IV
certification to the listed patent. Information on whether a patent
claims the drug substance or drug product in addition to whether the
patent claims one or more methods of use is required because a
505(b)(2) or ANDA applicant that avails itself of the statutory
provision that permits it to not seek approval of a method of use
claimed by the patent (and carve out from product labeling the method-
of-use information claimed by the patent) would still be required to
submit a patent certification with respect to any drug substance or
drug product claims covered by the same listed patent (see Letter from
Janet Woodcock, M.D., Director, CDER, to Rosemarie R. Wilk-Orescan,
Novo Nordisk Inc., and James F. Hurst, Winston & Strawn LLP, dated
December 4, 2008, regarding Docket Nos. FDA-2008-P-0343-0009 and FDA-
2008-P-0411-0006, available at http://www.regulations.gov) (Repaglinide
Citizen Petition Response). For example, a 505(b)(2) or ANDA applicant
may submit a statement under section 505(b)(2)(B) or
505(j)(2)(A)(viii), respectively, of the FD&C Act for a method-of-use
patent that does not claim a use for which the applicant is seeking
approval and a paragraph IV certification for any remaining drug
substance, drug product, or other method-of-use claims covered by the
same patent. This approach is sometimes described as a ``split
certification'' to the patent.
    We note that a 505(b)(2) or ANDA applicant that submitted a
paragraph IV certification in addition to a statement under section
505(b)(2)(B) or 505(j)(2)(A)(viii) of the FD&C Act must comply with the
notice requirements for a paragraph IV certification and may be subject
to a 30-month stay of approval if patent infringement litigation is
initiated within the statutory timeframe. An ANDA applicant that
submitted a paragraph IV certification and a statement pursuant to
section 505(j)(2)(A)(viii) of the FD&C Act to a listed patent also may
be eligible for 180-day exclusivity based on its paragraph IV
certification if the applicant is a ``first applicant'' and meets other
statutory and regulatory requirements.
    II.B.1.b. Drug substance patents that claim only a polymorph of the
active ingredient. Section 314.53(c)(2)(i)(M)(2) and (c)(2)(ii)(N)(2)
currently require submission of information on whether the patent
claims a polymorph (generally, a drug substance with a different
crystalline (including solvates and hydrates) or amorphous form of the
same drug substance) that is the same active ingredient as that
described in the pending NDA, amendment, or supplement. We explained in
the preamble to the June 2003 final rule that ``it would be consistent
to interpret `drug substance' for patent submission and listing
purposes as including certain drug substances having different physical
forms if they would be

considered the same active ingredient for ANDA approval purposes'' (68
FR 36676 at 36678).
    We are proposing to revise these regulations to state that an
applicant is only required to provide information on whether the patent
claims a polymorph that is the same active ingredient described in the
pending NDA, amendment, or supplement if the only basis on which the
patent is eligible for listing is that it claims the polymorph. Based
on comments received from industry on this issue (see April 2007
notice) and inquiries from applicants regarding completion of Forms FDA
3542a and 3542, we have tentatively concluded that our regulations need
to be modified. With respect to a patent that claims the drug substance
or drug product described in the pending NDA, amendment, or supplement
and one or more polymorphic forms of the drug substance, an applicant
is not required to provide information on whether the patent claims a
polymorph if the patent otherwise meets the statutory requirements for
submission of patent information regarding the drug substance or drug
product.
    Similarly, we are proposing to make conforming revisions to Sec.
314.53(b)(1), (b)(2), (c)(2)(i)(M)(3), and (c)(2)(ii)(N)(3) to provide
that the applicant certification regarding test data required by Sec.
314.53(b) applies only to patents that claim only a polymorph. This
provision also had generated confusion, and we are proposing revisions
for clarification.
    II.B.1.c. Method-of-use patents. Section 314.53(b)(1) currently
states that an applicant ``shall separately identify each pending or
approved method of use and related patent claim.'' This text has been
subject to differing interpretations by applicants as to whether our
regulations require submission of patent information (and completion of
Forms FDA 3542a and 3542) on a claim-by-claim basis. In the June 2003
final rule, we explained that we require identification of individual
patent claims for method-of-use patents to assist 505(b)(2) and ANDA
applicants in determining whether a listed method-of-use patent claims
a use for which the 505(b)(2) or ANDA applicant is not seeking approval
(see 68 FR 36676 at 36682 and 36685). In the April 2007 notice, we
clarified that ``consistent with our regulations at Sec.  314.53(b)(1),
. . . an applicant may list together multiple patent claims for each
pending or approved method of use. However, each pending or approved
method of use must be separately identified and therefore will require
separate listing(s) of method-of-use information in section 4 of Forms
FDA 3542a and 3542. Therefore, if a patent claims one or more methods
of use that apply to a pending application or approved product, each
pending or approved method of use would need to be listed separately
along with the patent claim number(s) for the patent claim(s) for the
pending or approved method of use. A single Form FDA 3542a or Form FDA
3542, as appropriate, may be used to list a patent claiming more than
one method of use, provided that each method of use is listed
separately along with the patent claim number(s) for the patent
claim(s) for the pending or approved method of use. This regulatory
approach accomplishes the statutory objective of providing adequate
information to permit ANDA and 505(b)(2) applicants to file statements
which assert that the method-of-use patent does not claim a use for
which the applicant is seeking approval'' (72 FR 21266 at 21268).
    We are proposing to revise Sec.  314.53(b)(1) by replacing the word
``claim'' with ``claim(s)'' in the phrase ``shall separately identify
each pending or approved method of use and related patent claim.'' This
proposed revision is intended to further clarify that an applicant may
list together multiple patent claims for a pending or approved method
of use on Forms FDA 3542a and 3542, respectively. However, each pending
or approved method of use must be separately identified and therefore
will require separate listing(s) of method-of-use information in
section 4 of Forms FDA 3542a and 3542.
    We also are proposing to revise Sec.  314.53(b)(1),
(c)(2)(i)(O)(2), (c)(2)(ii)(P)(2) and (c)(2)(ii)(P)(3) to enhance
compliance by NDA applicants with the requirements for identifying the
specific section(s) of product labeling that correspond to the method
of use claimed by the patent and, upon approval, describing the
approved method of use claimed by the patent, as required for
publication in the Orange Book. Proposed Sec.  314.53(b)(1) would
expressly require that if the scope of the method-of-use claim(s) of a
patent does not cover every use of the drug, the applicant must
identify only the specific sections of product labeling that correspond
to the specific portion(s) of the indication or other condition of use
claimed by the patent. The specific product labeling that corresponds
to the protected use may appear in sections of the labeling other than
``Indications and Usage.'' This proposed revision and conforming
revisions to proposed Sec.  314.53(c)(2)(i)(O)(2) and (c)(2)(ii)(P)(2)
would address situations in which the scope of the method of use
claimed by the patent is narrower than the indication or other
condition of use described in product labeling. In such cases, the NDA
applicant must identify only the specific sections of product labeling
that correspond to the portion(s) of the indication or other condition
of use claimed by the patent and not the broader indication or other
condition of use in the product labeling which may include, but not be
limited to, the use claimed by the patent. Accurate identification of
the specific sections of product labeling that correspond to the use
claimed by the patent is necessary to enable FDA to implement section
505(b)(2)(B) and (j)(2)(A)(viii) of the FD&C Act, which permit
505(b)(2) and ANDA applicants to omit protected conditions of use from
labeling. This information regarding product labeling also is necessary
for FDA to evaluate whether the omission of aspects of the listed
drug's labeling protected by patent would render the proposed drug
product less safe or effective than the listed drug for all remaining
non-protected conditions of use and preclude approval (see Sec.
314.127(a)(7); see also Sec.  314.94(a)(8)(iv)).
    Proposed Sec.  314.53(c)(2)(ii)(P)(3) would codify our longstanding
requirement that the NDA applicant's description of the patented method
of use (the ``use code'') required for publication in the Orange Book
must contain adequate information to assist FDA and 505(b)(2) and ANDA
applicants in determining whether a listed method-of-use patent claims
a use for which the 505(b)(2) or ANDA applicant is not seeking
approval. If the scope of the method-of-use claim(s) of the patent does
not cover every approved use of the drug, the NDA holder's ``use code''
must contain only the specific portion(s) of the indication or other
method of use claimed by the patent. This requirement is necessary to
effectively implement the statutory provisions that permit 505(b)(2)
and ANDA applicants to submit a statement that the applicant is not
seeking approval for the use claimed in the listed patent instead of a
patent certification to the listed patent with respect to the method of
use claim(s) (see section 505(b)(2)(B) and (j)(2)(C)(viii) of the FD&C
Act, respectively). We require the NDA holder to submit an accurate
description, subject to the verification requirements in Sec.
314.53(c)(2)(ii)(R), of the method of use within the scope of the
patent that claims an approved use of the drug to implement these
statutory provisions. As the U.S. Supreme Court noted in Caraco Pharm.
Labs. v. Novo

Nordisk A/S: ``An overbroad use code . . . throws a wrench into the
FDA's ability to approve generic drugs as the statute contemplates''
(132 S. Ct. 1670, at 1684 (2012)).
    II.B.1.d. Patents previously submitted for listing. We are
proposing to revise Sec. Sec.  314.53(c)(2)(i)(J) and (c)(2)(ii)(K) to
remove the requirement that an applicant provide information regarding
whether the patent has been submitted previously for the NDA or
supplement. This requirement was intended to assist the Orange Book
staff with their administrative listing responsibilities (see 68 FR
36676 at 36686). In response to a request for clarification of the
purpose of this inquiry (see 72 FR 21266 at 21269) and to streamline
the patent information submission requirements, we are proposing to
revise Sec. Sec.  314.53(c)(2)(i)(J) and (c)(2)(ii)(K) to request
information on whether the patent is a reissuance of a patent submitted
previously for listing in the Orange Book for the NDA or supplement,
including the original patent number of the listed patent (see section
II.B.1.e).
    If a patent has been submitted previously for listing in the Orange
Book, we currently request information on whether the expiration date
is a new expiration date (Sec.  314.53(c)(2)(i)(K) and (c)(2)(ii)(L)).
For example, a patent expiration date may be extended after NDA
approval in response to a request for patent term restoration pursuant
to 35 U.S.C. 156 (see proposed Sec.  314.53(f)(2)(ii), discussed in
section II.B.4.b). We are continuing to request this information.
    We note that our proposed revisions to the patent information
submission requirements for supplements to an approved NDA (see section
II.B.2.a) are designed to identify, among other things, whether patents
previously submitted for listing for the underlying NDA continue to
claim the changed product as approved in the supplement.
    II.B.1.e. Reissued patents. We are proposing certain revisions to
our regulations to describe our requirements regarding submission of
information related to patents that have been reissued by the PTO.
Generally, a patent may be reissued to correct certain errors in the
scope of claims or defects in a specification or drawing that otherwise
would have invalidated, in whole or in part, the patent (see 35 U.S.C.
251). Accordingly, a reissued patent may affect both the patent
certification or statement submitted by a 505(b)(2) or ANDA applicant
and the infringement claims that could be asserted by the patent owner
or NDA holder.
    Although we recognize that the original patent is surrendered upon
patent reissuance (see 37 CFR 1.178(a)), we are proposing to treat the
original patent and the reissued patent as a ``single bundle'' of
patent rights, albeit patent rights that may have changed with
reissuance, for purposes of administering the patent certification
requirements of the FD&C Act and any 30-month stay of approval or 180-
day exclusivity that relates to a paragraph IV certification to the
original patent (see discussion in section II.E.4). FDA's role in
listing patents remains ministerial (see 59 FR 50338 at 50349, October
3, 1994 (1994 final rule); 68 FR 36676 at 36687 (June 2003 final
rule)); however, we are mindful of the implications of reissued patents
in fulfilling our statutory obligations regarding implementation of the
patent certification and statement, 30-month stay, 180-day exclusivity,
and tentative approval provisions of the FD&C Act. We are proposing
these revisions to describe the responsibilities of an NDA applicant
associated with listing a reissued patent. The requirements for a
505(b)(2) or ANDA applicant to provide an appropriate patent
certification or statement to a reissued patent are discussed in
section II.E.4).
    We currently receive submissions of patent information for reissued
patents and list those patents that are eligible for listing in the
Orange Book. Reissued patents are identified by the PTO with the
letters ``RE'' preceding the patent number and, because a patent is
reissued for the unexpired part of the term of the original patent,
have the same expiration date as the original patent. If the scope of
claims was narrowed or broadened upon reissuance, the NDA applicant or
holder may submit a reissued patent for listing in the Orange Book with
a revised designation of whether the patent claims the drug substance,
drug product, and/or a method or use, or with a revised use code.
    Proposed Sec.  314.53(c)(2)(i)(J) and (c)(2)(ii)(K) would provide
that an NDA applicant or holder is required to include information on
whether a patent submitted for listing is a reissuance of a patent
previously submitted for listing for the NDA or supplement. Submission
of patent information for reissued patents is subject to the 30-day
timeframe for timely filed patent information set forth in section
505(c)(2) of the FD&C Act. As discussed further in section II.B.2.b,
the timely filing of patent information for a reissued patent
(including a reissued patent with a broadened scope of claims) does not
alter the patent certification obligations of a 505(b)(2) or ANDA
applicant whose application was pending when the original patent was
filed by the holder of an approved application for listing more than 30
days after patent issuance (``late listed''). In other words, if a
505(b)(2) or ANDA applicant is not required to provide a patent
certification or statement to the original patent pursuant to Sec.
314.50(i)(4) or Sec.  314.94(a)(12)(vi) because the patent was late
listed, the 505(b)(2) or ANDA applicant would not be required to
provide a patent certification or statement to the reissued patent even
if timely filed following reissuance. This approach recognizes that the
original and reissued patents comprise a ``single bundle'' of patent
rights, which first became relevant to approval of 505(b)(2)
applications and ANDAs with the submission of the patent information
prior to reissuance. As described in section II.E.3, the date of
submission of the original patent information also determines the
availability of a 30-month stay arising from patent infringement
litigation resulting from notice of a paragraph IV certification to the
original or reissued patent (see section 505(c)(3)(C) and
(j)(5)(B)(iii) of the FD&C Act).
    An original patent that has been reissued would remain listed in
the Orange Book until FDA determined that any first ANDA applicant is
no longer eligible for 180-day exclusivity or the 180-day exclusivity
period has expired (see section II.E.4). We intend to designate
original patents that have been reissued and remain listed in the
Orange Book for this reason with the suffix ``*RE'' based on
information submitted by the NDA applicant or holder in accordance with
Sec.  314.53(c)(2)(ii)(K). In the absence of this designation, an
applicant that submits an ANDA after a reissued patent is listed in the
Orange Book may not provide a patent certification or statement with
respect to the original patent. Instead, the ANDA applicant must
provide a patent certification or statement to the reissued patent.

    Should the scope of a reissued patent be narrowed such that it is
no longer eligible for listing under section 505(b)(1) or 505(c)(2) of
the FD&C Act, the NDA holder is required to request that the patent or
patent information be removed from listing in the Orange Book (``patent
delisting''), subject to the exceptions set forth in proposed Sec.
314.53(f)(2) (see discussion in section II.B.4.b).
II.B.2. When and Where To Submit Patent Information (Proposed Sec.
314.53(d))
    Table 3 summarizes the proposed changes regarding when and where to
submit patent information:

 Table 3--Highlights of Proposed Changes Regarding Submission of Patent
                             Information \1\
------------------------------------------------------------------------
                                              Proposed revisions to
          Current regulations                      regulations
------------------------------------------------------------------------
Supplements (Sec.   314.53(d)(2)(i))...  Supplements (Sec.
                                          314.53(d)(2)(i)).
 Applicant must submit patent     Applicant must submit
 information required under Sec.          patent information required
 314.53(c) for a patent that claims the   under Sec.   314.53(c) for a
 drug, drug product, or method of use     patent that claims the drug
 for which approval is sought in a        substance, drug product, or
 supplement:                              method of use for which
(A) to change the formulation;.........   approval is sought in a
(B) to add a new indication or other      supplement:
 condition of use;.                      (A) to change the dosage form
(C) to change the strength;............   or route of administration;
(D) to make any other patented change    (B) to change the strength; or
 regarding the drug, drug product, or    (C) to change the drug product
 method of use..                          from prescription to OTC use.
Supplements (Sec.   314.53(d)(2)(ii))..  Supplements (Sec.
If an applicant submits a supplement      314.53(d)(2)(ii)).
 for a change described in Sec.          If an applicant submits a
 314.53(d)(2)(i), the following patent    supplement for a change other
 information submission requirements      than one described in Sec.
 apply:.                                  314.53(d)(2)(i), the following
                                          patent information submission
                                          requirements apply:
     If previously submitted      If previously
     patent information claims the        submitted patent information
     changed product, the applicant       claims the changed product,
     must submit a certification with     the applicant is not required
     the supplement identifying the       to resubmit this patent
     patents that claim the changed       information unless the
     product.                             description of the patented
                                          method of use would change
                                          upon approval of the
                                          supplement, and FDA will
                                          continue to list this patent
                                          information for the product;
     If no patents, including     If previously
     previously submitted patents,        submitted patent information
     claim the changed product, it must   no longer claims the changed
     so certify.                          product, the applicant must
                                          submit a request to remove
                                          that patent information from
                                          the list at the time of
                                          approval of the supplement;
                                          If one or more
                                          existing drug substance, drug
                                          product, or method-of-use
                                          patents claim the changed drug
                                          product for which approval is
                                          sought in the supplement and
                                          such patent information has
                                          not been submitted to FDA, the
                                          applicant must submit the
                                          patent information required
                                          under Sec.   314.53(c).
Patent information deadline (Sec.        Newly issued patents (Sec.
 314.53(d)(3)).                           314.53(d)(3)).
     If a patent is issued for    If a patent is issued
     a drug, drug product, or method of   for a drug substance, drug
     use after an application is          product, or method of use
     approved, the applicant must         after an NDA is approved, the
     submit to FDA the required patent    applicant must submit to FDA
     information within 30 days of the    the required patent
     date of patent issuance.             information within 30 days of
                                          the date of patent issuance.
                                          If the required patent
                                          information is not submitted
                                          within 30 days of patent
                                          issuance, FDA will list the
                                          patent, but patent
                                          certifications will be
                                          governed by the provisions
                                          regarding untimely filed
                                          patents at Sec.  Sec.
                                          314.50(i)(4) and (i)(6) and
                                          314.94(a)(12)(vi) and
                                          (a)(12)(viii).
Late submission of patent information    Untimely filing of patent
 (Sec.  Sec.   314.50(i)(4) and           information (Sec.  Sec.
 314.94(a)(12)(vi)).                      314.50(i)(4) and
                                          314.94(a)(12)(vi)).
     [Provision directed to       Except as provided in
     submission of required patent        Sec.   314.53(f)(1), an NDA
     information in general.].            holder's amendment to the
                                          description of the approved
                                          method(s) of use claimed by
                                          the patent will be considered
                                          untimely filing of patent
                                          information if:
                                         --the amendment is submitted
                                          more than 30 days after patent
                                          issuance and it is not related
                                          to a corresponding change in
                                          approved product labeling; or
                                         --the amendment is submitted
                                          more than 30 days after a
                                          corresponding change in
                                          approved product labeling.
Copies (Sec.   314.53(d)(4))...........  Submission of Forms FDA 3542a
                                          and 3542 (Sec.
                                          314.53(d)(4)).
     Applicant must submit an     Applicant must submit
     archival copy and a copy for the     patent information required by
     chemistry, manufacturing, and        Sec.   314.53(c)(1) and
     controls (CMC) section of the        (c)(2)(i), Sec.   314.50(h),
     review copy to the CDER Central      or Sec.   314.70(f) on Form
     Document Room.                       FDA 3542a to the CDER Central
                                          Document Room at the address
                                          identified on FDA's Web site.
                                         [cir] Form FDA 3542a should not
                                          be submitted to the Orange
                                          Book Staff in the Office of
                                          Generic Drugs.
     Applicant must submit        Applicant must submit
     patent information by letter         patent information required by
     separate from, but at the same       Sec.   314.53(c)(1) and
     time as, submission of the           (c)(2)(ii) on Form FDA 3542 to
     supplement.                          the Office of Generic Drugs,
                                          Document Room, Attention:
                                          Orange Book Staff.
Submission date (Sec.   314.53(d)(5))..  Submission date (Sec.
                                          314.53(d)(5)).
     Patent information will be   Patent information
     considered submitted to FDA as of    will be considered submitted
     the date the information is          to FDA for purposes of Sec.
     received by the Central Document     314.53(d)(3) as of the earlier
     Room.                                of the date the information
                                          submitted on Form FDA 3542 is
                                          date-stamped by the Office of
                                          Generic Drugs, Document Room,
                                          or officially received
                                          electronically by FDA through
                                          the Electronic Submissions
                                          Gateway.
------------------------------------------------------------------------
\1\ These highlights describe important proposed revisions to our
  regulations, but should not be relied upon in place of the proposed
  regulation.

    II.B.2.a. Submission of patent information for NDA supplements
(proposed Sec.  314.53(d)(2)). We are proposing to revise the
requirements for submission of patent information for NDA supplements
to reduce duplicative submissions of patent information and enhance
efficiency.
    Section 314.53(c) requires submission of patent information for
certain types of supplements that relate to the drug product or a
method of using the drug product, namely those supplements that seek
approval to change the formulation, add a new indication or other
condition of use, change the strength, or make any other patented
change regarding the drug, drug product, or any method of use (see
Sec.  314.53(d)(2)(i)(A) through (d)(2)(i)(D)). This approach avoided
unnecessary resubmission of patent information with supplements that
did not involve a change to the drug product or a method of using the
product or involved a change that could not be patented (see 54 FR
28872 at 28910, July 10, 1989; and 59 FR 50338 at 50344). We are
proposing to eliminate certain of these patent information submission
requirements for supplements that seek approval for a change to an
approved product and for which existing patents listed in the Orange
Book for the specific drug product that is the subject of the
supplement continue to claim the changed product (see proposed Sec.
314.53(d)(2)(ii)(A)). These proposed revisions to our regulations also
address a comment submitted by an association representing research-
based pharmaceutical and biotechnology companies that ``submission of
Forms FDA 3542a and 3542 with submission and upon approval,
respectively, of an NDA supplement is redundant where the information
has not changed since the form last was filed, imposes a burden on
sponsors, and serves no statutory purpose'' (72 FR 21266 at 21270).
    Our proposed revisions to Sec.  314.53(d)(2) would create two broad
categories of supplements for purposes of patent information submission
based on whether the supplement is a type for which approval would
result in a new entry in the Orange Book. For supplements that seek
approval for a change that will result in a new entry in the Orange
Book (e.g., a change to the dosage form, route of administration,
strength (including changes to concentration or total drug content), or
prescription drug status (i.e., change the drug product from
prescription use to over-the-counter (OTC) use)), an applicant must
continue to submit patent information required under Sec.  314.53(c)
with submission of the supplement and following approval, respectively.
Although these types of changes may not necessarily result in a
submission of different patent information, by requiring an NDA holder
to submit complete patent information for a supplement that, if
approved, would result in a new entry in the Orange Book, we ensure
that patent information listed for the new entry clearly expresses the
NDA holder's view regarding which patent(s) claim the drug or a method
of using the drug as approved in the supplement. For example, different
strengths of a drug product may have different patent coverage with
respect to method-of-use patents that claim a dosing regimen or
indication. In such a case, patent information would be required to be
submitted with the filing of the NDA supplement and would be required
to be submitted upon approval of the NDA supplement. This submission of
patent information on Forms FDA 3542a and 3542 would, among other
things, identify with specificity the new method of use claimed by the
patent with reference to the proposed or approved labeling,
respectively, for the drug product. If the patents listed for the
approved NDA also claim the drug or method of using the drug for which
approval is sought in the NDA supplement, we will permit an applicant
to submit a statement declaring that the patents currently listed for a
specific NDA (identified by NDA number and product number as listed in
the Orange Book) also claim the drug or method of using the drug for
which approval is sought in the NDA supplement, if this statement is
accompanied by the signed patent declaration verification required by
Sec.  314.53(c)(2)(i)(Q) and (c)(2)(ii)(R) and if patent information
required by Sec.  314.53(c)(2)(ii) previously was submitted (see June
2003 final rule (68 FR 36676 at 36681)). This proposed approach
fulfills the statutory requirements for patent listing set forth in
section 505(b)(1) and (c)(2) of the FD&C Act and ensures that patents
listed for separate entries for drug products in the Orange Book are
supported by an unambiguous submission of applicable patent
information.
    It should be noted that proposed Sec.  314.53(d)(2)(i)(A) is
intended to encompass only the types of changes in dosage form or route
of administration that may be submitted as an NDA supplement and does
not apply to proposed changes in dosage form or route of administration
that should be submitted as a separate application (see guidance for
industry entitled ``Submitting Separate Marketing Applications and
Clinical Data for Purposes of Assessing User Fees'' (December 2004),
available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM079320.pdf)
(Separate Marketing Application Guidance). Similarly, we note that
proposed Sec.  314.53(d)(2)(i)(C) describes supplements to change the
drug product from prescription use to OTC status for all conditions of
use, because a separate marketing application would be required for a
change to OTC status for fewer than all conditions of use.
    Our proposal would eliminate the automatic requirement for
submission of patent information with a supplement seeking approval for
a change in formulation or new indication or other condition of use
(except for those conditions of use described in Sec.
314.53(d)(2)(i)). However, new submission of patent information would
still be required if the patent(s) that claim the product as changed by
the supplement differ from the patent(s) currently listed for the drug
product. For supplements that seek approval for a change to a listed
product that would not result in a new entry in the Orange Book (i.e.,
a change other than one of the changes described in proposed Sec.
314.53(d)(2)(i)), an applicant needs to evaluate whether each patent
for which information is currently listed in the Orange Book for the
drug product continues to claim the changed product. If existing
patents listed for the product approved in the original application
claim the product as changed by the supplement, the applicant is not
required to resubmit this patent information unless the description of
the method of use claimed by a patent would change upon approval of the
supplement (see proposed Sec.  314.53(d)(2)(ii)(A)). (In this regard,
we note that an untimely filed patent that claims the product approved
in the original application cannot be transformed into a timely filed
patent with submission of a supplement.)
    If, however, a listed patent no longer claims the product as
changed by the supplement (e.g., a new formulation is no longer claimed
by a patent listed for the original formulation of the drug product),
then the applicant must submit a request to correct or remove the
patent information from the list in accordance with proposed Sec.
314.53(f)(2) at the time of approval of the supplement.
Correspondingly, if one or more existing patents claim the product

as changed by the supplement (e.g., a supplement seeking approval for a
new indication) and this patent information has not been submitted to
FDA, the applicant must submit the patent information with the
supplement and following approval. The requirement in proposed Sec.
314.53(d)(2)(ii)(C) also would apply to submission of patent
information for a patent currently listed for the drug as approved in
the original application that claims the drug approved in the
supplement in a new way (e.g., a new or additional method of use) and
for which the patent information would be required to be submitted
under Sec.  314.53(c). In this case, the applicant would be required to
comply with Sec.  314.53(c) and submit patent information describing
the new or additional method of use claimed by the patent with the
supplement and following approval.
    As noted previously in this section of the document, the Agency has
received comments criticizing as redundant the requirement for
submission of Forms FDA 3542a and 3542 with submission and upon
approval, respectively, of an NDA supplement where the information has
not changed since the form last was filed (see April 2007 notice).
Section 505(b)(1) of the FD&C Act requires the submission of patent
information with the filing of a supplement to an NDA. To the extent
that patents currently listed for the drug product continue to claim
the product as changed by the supplement, we interpret the statute to
not require resubmission of duplicative patent information. In
circumstances other than those described in proposed Sec.
314.53(d)(2)(ii)(A), an applicant or sponsor must submit required
patent information with submission and upon approval of a supplement.
This requirement facilitates the prompt listing of patent information
postapproval by requiring applicants to complete their initial
assessment of relevant patents with submission of their application and
during the pendency of its review.
    We are proposing a conforming revision to Sec.  314.70(f) to
clarify that an applicant that submits a supplement to an NDA
(including a 505(b)(2) application) also must comply with the patent
information requirements under Sec.  314.53.
    II.B.2.b. Untimely filing of patent information (proposed
Sec. Sec.  314.53(d)(3), 314.50(i)(4), and 314.94(a)(12)(vi)). We are
proposing to supplement Sec.  314.53(d)(3) to expressly describe our
longstanding practice with respect to listing untimely filed patents.
Proposed Sec.  314.53(d)(3) states that if the required patent
information is not submitted within 30 days of the issuance of the
patent, FDA will list the patent, but patent certifications will be
governed by the provisions regarding untimely filed patents in
Sec. Sec.  314.50(i)(4) and (i)(6) and 314.94(a)(12)(vi) and
(a)(12)(viii) of this part. We also are proposing to revise Sec. Sec.
314.50(i)(4) and 314.94(a)(12)(vi) to include certain amendments to the
description of the approved method(s) of use claimed by the patent
within the category of untimely filed patent information.
    Section 505(c)(2) of the FD&C Act requires an NDA holder to file
patent information for a patent issued after the date of approval of
the application within 30 days of patent issuance. (As clarified in
proposed Sec.  314.53(c)(2)(ii), this statutory requirement for timely
filing does not apply to patent information submitted prior to approval
of an NDA or supplement, even if the patent information is submitted to
FDA more than 30 days after the patent is issued by the PTO.)
    Section 505(c)(2) of the FD&C Act further directs the Agency to
publish information on the newly-issued patent upon its submission, and
we have interpreted this statutory provision to require listing in the
Orange Book irrespective of whether the patent information has been
timely filed. Although we list untimely filed patents pursuant to
section 505(c)(2) of the FD&C Act, we generally do not require an
applicant with a pending 505(b)(2) application or ANDA to provide a
patent certification to a patent for which the NDA holder failed to
comply with the statutory timeframe for submission of patent
information after approval. Accordingly, the untimely filed patent will
neither delay approval of a pending 505(b)(2) application or ANDA until
patent expiration nor necessitate a carve-out of information related to
a patented method of use.
    Although an applicant with a pending 505(b)(2) application or ANDA
that references the drug product generally would not be required to
submit a patent certification to an untimely filed patent that was
late-listed as to the pending 505(b)(2) application or ANDA, we would
permit an applicant to submit and maintain a patent certification
(including a paragraph IV certification) or a statement pursuant to
section 505(b)(2)(B) or 505(j)(2)(B)(viii) of the FD&C Act, if desired.
For example, a 505(b)(2) or ANDA applicant may wish to submit a
paragraph IV certification to challenge the late-listed patent and
obtain patent certainty (i.e., determine whether the NDA holder or
patent owner will initiate a patent infringement action against the
applicant) instead of possibly marketing at risk.
    We also are proposing to revise Sec. Sec.  314.50(i)(4) and
314.94(a)(12)(vi) to state that, except as provided in Sec.
314.53(f)(1), an NDA holder's amendment to the description of the
approved method(s) of use claimed by the patent will be considered
untimely filing of patent information if:
     The amendment is submitted more than 30 days after patent
issuance and it is not related to a corresponding change in approved
product labeling or
     the amendment is submitted more than 30 days after a
corresponding change in approved product labeling.

This proposed revision is consistent with the objective of ensuring
that prospective 505(b)(2) and ANDA applicants have timely notice of
changes to the asserted patent coverage for a listed drug. In addition,
proposed Sec. Sec.  314.50(i)(4) and 314.94(a)(12)(vi) would complement
proposed revisions to Sec.  314.53 that are intended to enhance NDA
holders' compliance with the requirement to accurately identify the
specific sections of product labeling that correspond to the use
claimed by the patent (see section II.B.1.c). If an amendment to change
the patent use code is not related to a corresponding change in
approved product labeling and is submitted more than 30 days after
patent issuance (or patent reissuance), then the patent information is
properly considered untimely filed. In accordance with Sec. Sec.
314.50(i)(4) and 314.94(a)(12)(vi), an untimely filed method-of-use
patent does not require a patent certification or statement and would
not delay approval of a pending 505(b)(2) application or ANDA.
Similarly, if an amendment to change the patent use code is submitted
more than 30 days after a corresponding change in approved product
labeling, then the amendment lacks a clear temporal or substantive link
to the specific section(s) of approved product labeling claimed by the
patent, and the patent information is untimely filed.
    An applicant with a pending 505(b)(2) application or ANDA that
seeks to confirm that a newly listed patent was untimely filed (and may
not require a patent certification in accordance with Sec.
314.50(i)(4) or Sec.  314.94(a)(12)(vi)) should contact the Orange Book
staff. Irrespective of whether the patent was untimely filed (and thus
late-listed as to the pending 505(b)(2) application or ANDA) or timely
filed (and thus ``later listed'' as to the pending 505(b)(2)
application or ANDA), a paragraph IV certification submitted for a
patent filed with FDA after the date on which a

505(b)(2) application or ANDA (that is later determined to be
substantially complete) was submitted will not give rise to a 30-month
stay (see section 505(c)(3)(C) and (j)(5)(B)(iii) of the FD&C Act and
section II.G).
    We note, however, that a 505(b)(2) application or ANDA submitted
after the untimely filed patent is listed in the Orange Book is
required to submit an appropriate patent certification or statement to
the patent. As we explained in the 1994 final rule, ``[t]he approach
adopted by the Agency as best embodying the compromise adopted by
Congress requires that if an NDA applicant submits required patent
information on an approved drug product more than 30 days after
issuance of the patent, FDA will publish the untimely information, but
will not require ANDA and 505(b)(2) applicants with pending
applications that have previously submitted a certification, i.e. those
applicants that would be prejudiced by the late submission, to
recertify to the new patent. Only applicants that initially submit
ANDA's or 505(b)(2) applications after the submission of the patent
information or whose pending applications do not contain a valid
certification at the time of submission would be required to submit a
certification as to that patent. . . . While this could result in two
categories of ANDA's for a pioneer drug, those without certifications
for the late-filed patent and those with certifications for that
patent, this approach is the best means for discouraging manipulation
of the patent filing scheme and providing optimum notice of applicable
patents'' (59 FR 50338 at 50340, response to comment 7).
    We remind NDA holders that patents issued after approval of a drug
under section 505(c) of the FD&C Act include reissued patents (see
section II.B.1.e) as well as patents that claim a drug product listed
in the discontinued section of the Orange Book. With reference to the
latter category, we note that a 505(b)(2) or ANDA applicant may rely
upon a drug product listed in the discontinued section of the Orange
Book to the extent that the product was not withdrawn for reasons of
safety or effectiveness (see Sec.  314.151 with respect to ANDAs).
Accordingly, we encourage NDA holders to ensure that they continue to
comply with the statutory requirements for patent listing for products
that have been discontinued from marketing.
    We also are proposing to revise Sec.  314.50(i)(4) to remove an
incorrect reference to the possible submission of a certification under
Sec.  314.50(i)(1)(ii) after the NDA holder's untimely filing of patent
information. If a 505(b)(2) applicant is required to submit a patent
certification to untimely filed patent information as provided in
proposed Sec.  314.50(i)(4), a ``no relevant patents'' statement under
Sec.  314.50(i)(1)(ii) would not be an acceptable patent certification.
    Finally, we are proposing to revise the heading for Sec.
314.53(d)(3) to ``newly issued patents'' to better characterize the
text and emphasize its applicability to patents issued after approval
of an NDA or supplement. We also are proposing to revise the heading
for proposed Sec. Sec.  314.50(i)(4) and 314.94(a)(12)(vi) to
``untimely filing of patent information'' and to make conforming
revisions to the text of these sections for consistent use of
terminology.
    II.B.2.c. Where to send submissions of Forms FDA 3542a and 3542
(proposed Sec.  314.53(d)(4)). We are proposing to require that patent
information filed on Form FDA 3542 upon and after approval of an NDA or
supplement be submitted directly to the Orange Book staff through the
OGD Document Room. The Orange Book staff will send an archival copy of
this patent information to CDER's Central Document Room for filing with
the NDA.
    Our proposal to require that NDA holders submit post-approval
patent information directly to the Orange Book staff is intended to
facilitate prompt listing of patent information in the Orange Book
after Form FDA 3542 has been officially received by the Agency.
Currently, many NDA holders submit a duplicate or courtesy copy of Form
FDA 3542 to the Orange Book staff electronically or via facsimile at
the time of their submission of Form FDA 3542 to CDER's Central
Document Room. This patent information is listed in the Orange Book
upon receipt by the Orange Book staff, and the Orange Book explains
that the date on which patent information is published ``may not
reflect the official receipt date as described in 21 CFR
314.53(d)(5).'' However, this practice may result in publication of
patent information prior to receipt by the official repository
identified in our regulations and cause confusion for prospective first
applicants and applicants with a pending 505(b)(2) application or ANDA
seeking to determine whether or not the patent is late-listed. Proposed
Sec.  314.53(d)(4) designates the OGD Document Room as an official
repository for submissions of Form FDA 3542, and proposed Sec.
314.53(d)(5) (see section II.B.2.d) clarifies that the submission date
of patent information provided by an NDA holder after approval of an
application is the earlier of the date on which Form FDA 3542 is date-
stamped by the OGD Document Room or officially received electronically
by FDA though the Electronic Submissions Gateway. These proposed
revisions to the regulations are intended to enhance efficiency and
ensure that patent information is promptly listed after its receipt.
    We note, however, that patent information submitted on Form FDA
3542a with the filing of an NDA, amendment, or supplement, and prior to
approval of the application must continue to be submitted directly to
the NDA as required by Sec.  314.50(h) or Sec.  314.70(f), as
appropriate. An applicant should not submit a copy of Form FDA 3542a to
the Orange Book staff; the Orange Book staff should only receive patent
information submitted after approval of the NDA or supplement. An
applicant should not submit a copy of the patent to FDA with submission
of Form FDA 3542a or 3542.
    II.B.2.d. Submission date of patent information (proposed Sec.
314.53(d)(5)). We are proposing to revise Sec.  314.53(d)(5) to
clarify, for purposes of Sec.  314.53(d)(3), that the submission date
of patent information provided by an NDA holder after approval of an
application is the earlier of the date on which Form FDA 3542 is date-
stamped by the OGD Document Room or officially received electronically
by FDA though the Electronic Submissions Gateway (i.e., at the
completion of electronic transmission). Our current regulations state
that the information shall be considered submitted to FDA on the date
it is received by the Central Document Room. We note that patent
information sent to another location at FDA is not considered received
by FDA for purposes of Sec.  314.53(d)(3) on timely filing and a
505(b)(2) or ANDA applicant's patent certification obligations pursuant
to Sec.  314.50(i)(4) and (i)(6) or Sec.  314.94(a)(12)(vi) and
(a)(12)(viii), respectively, unless it is sent to the official
repository identified in the regulation.
    These proposed revisions are intended to remove any ambiguity about
the date of submission in light of the implications of untimely filing
of patent information on the patent certification obligations of
505(b)(2) applicants and ANDA applicants that rely upon the listed drug
(see Sec. Sec.  314.50(i)(4) and 314.94(a)(12)(vi)). In this regard, we
note that the patent certification obligations of a 505(b)(2) or ANDA
applicant arise upon the receipt by the official repository at FDA of
the NDA holder's submission of patent information for a listed drug
rather than the timing of publication of the patent

information in the Orange Book (see section 505(b)(2)(A) and
(j)(2)(A)(vii) of the FD&C Act; see also Teva Pharms., USA, Inc. v.
Leavitt, 548 F.3d 103, at 108 (D.C. Cir. 2008) (noting that FDA ``has
consistently required ANDA applicants to certify to patents recently
submitted to FDA, even if FDA had not yet published the patent in any
version of the Orange Book'')).
    However, for purposes of eligibility for 180-day exclusivity, an
ANDA applicant is not permitted to submit a paragraph IV certification
to a patent (e.g., a recently issued patent that claims the RLD) before
the first working day after the day the patent is listed in the Orange
Book (see section II.D.1.b.ii and II.E.4).
    In addition, proposed Sec.  314.53(d)(5) would change the addressee
to whom submission of Form FDA 3542 should be sent from the Central
Document Room to the OGD Document Room or the Electronic Submissions
Gateway, consistent with proposed Sec.  314.53(d)(4) discussed in
section II.B.2.c.
II.B.3. Public Disclosure of Patent Information (Proposed Sec.
314.53(e))
    We are proposing to delete the reference in Sec.  314.53(e) to
monthly supplements to the Orange Book because the Agency no longer
arranges for publication of monthly printed supplements to the Orange
Book. Patent information listed in the Orange Book, which may be
accessed from the Agency's Web site, has been updated on a daily basis
for several years. This correction to Sec.  314.53(e) is consistent
with our proposed revision of the definition of ``the list'' in Sec.
314.3(b) to mean the list of approved drug products published in FDA's
current ``Approved Drug Products With Therapeutic Equivalence
Evaluations'' available electronically on FDA's Web site at http://www.fda.gov/cder.
    Section 314.53(e) provides that copies of the patent information
submitted on Form FDA 3542 may be requested from FDA's Freedom of
Information Staff. We are proposing to revise Sec.  314.53(e) to
replace the reference to a request for copies of the ``file'' to copies
of the ``submitted patent information.'' This revision is proposed for
clarity and does not represent a substantive change. We note, for
example, that some prospective 505(b)(2) or ANDA applicants have
requested copies of the patent information submitted on Form FDA 3542
for patents listed for a listed drug in the Orange Book to determine
the scope of the labeling identified by the NDA holder as relating to
the use claimed by the patent. Copies of Form FDA 3542 also have been
requested to obtain address information for the agent or representative
authorized to receive notice of patent certification if the patent
owner or NDA holder does not reside or have a place of business in the
United States. We anticipate additional requests for the information
submitted on Form FDA 3542 and may elect to proactively post on FDA's
Web site a copy of Form FDA 3542 for patents listed in the Orange Book
in advance of a request under the Freedom of Information Act (see
Presidential Documents, Memorandum for the Heads of Executive
Departments and Agencies on Transparency and Open Government (January
21, 2009) (74 FR 4685, January 26, 2009); see also Office of the
Attorney General, Memorandum for the Heads of Executive Departments and
Agencies on The Freedom of Information Act (March 19, 2009), available
at http://www.usdoj.gov/ag/foia-memo-march2009.pdf).
II.B.4. Correction or Change of Patent Information (Proposed Sec.
314.53(f))
    We are proposing to revise Sec.  314.53(f) to differentiate the
procedure for correction or change of patent information by the NDA
holder (proposed Sec.  314.53(f)(2)) from the procedure for requests by
persons other than the NDA holder. Proposed Sec.  314.53(f) also would
address certain issues that have arisen regarding method-of-use patents
and enhance FDA's response to challenges to the accuracy or relevance
of submissions of this patent information to the Agency. We are
proposing to redesignate the current text of Sec.  314.53(f) as Sec.
314.53(f)(1). We are proposing to add new Sec.  314.53(f)(2) to
implement section 505(j)(5)(D)(i)(I)(bb)(CC) of the FD&C Act, as added
by the MMA, and to make other changes for the efficient enforcement of
the FD&C Act.
    Table 4 summarizes the proposed changes related to correction or
change of patent information:

 Table 4--Highlights of Proposed Changes Regarding Correction or Change
                        of Patent Information \1\
------------------------------------------------------------------------
                                              Proposed revisions to
          Current regulations                      regulations
------------------------------------------------------------------------
Correction of patent information errors  Correction or change of patent
 (Sec.   314.53(f)).                      information--Requests by
                                          persons other than the NDA
                                          holder (Sec.   314.53(f)(1)).
 If any person disputes the       If any person disputes
 accuracy or relevance of patent          the accuracy or relevance of
 information submitted to FDA under       patent information submitted
 Sec.   314.53 and published by FDA in    to FDA under Sec.   314.53 and
 the list, that person must first         published by FDA in the list,
 notify FDA (OGD Document Room, Attn:     that person must first notify
 Orange Book Staff) in writing stating    FDA (OGD Document Room, Attn:
 the grounds for disagreement. FDA then   Orange Book Staff) in a
 will request that the NDA holder         written or electronic
 confirm the correctness of the patent    communication titled
 information..                            ``314.53(f) Patent Listing
                                          Dispute'' that states the
                                          grounds for disagreement. FDA
                                          then will request that the NDA
                                          holder confirm the correctness
                                          of the patent information
                                          within 30 days.
                                          For listed patents
                                          that claim an approved method
                                          of using the drug product, FDA
                                          will request that the NDA
                                          holder confirm the correctness
                                          of the ``Use Code'' in the
                                          Orange Book, and provide
                                          information on the specific
                                          approved use claimed by the
                                          patent that enables FDA to
                                          make a determination in
                                          accordance with section
                                          505(b)(2)(B) or
                                          (j)(2)(C)(viii) of the FD&C
                                          Act.
 Unless the NDA holder            Unless the NDA holder
 withdraws or amends its patent           withdraws or amends its patent
 information in response to FDA's         information in response to
 request to confirm the correctness of    FDA's request to confirm the
 the patent information, FDA will not     correctness of the patent
 change the patent information in the     information, FDA will not
 list.                                    change the patent information
                                          in the list.
                                         --If there is insufficient
                                          information to make a
                                          determination in accordance
                                          with section 505(b)(2)(B) or
                                          (j)(2)(C)(viii) of the FD&C
                                          Act and the NDA holder has
                                          confirmed the correctness of
                                          its description of the
                                          specific approved use claimed
                                          by the patent, the Agency will
                                          review the proposed labeling
                                          for the 505(b)(2) application
                                          or ANDA with deference to the
                                          505(b)(2) or ANDA applicant's
                                          interpretation of the scope of
                                          the patent.

                                         Correction or change of patent
                                          information--Requests by the
                                          NDA holder (Sec.
                                          314.53(f)(2)).
                                          If the NDA holder
                                          determines that a patent or
                                          patent claim no longer meets
                                          the statutory requirements for
                                          listing, the NDA holder must
                                          promptly notify FDA to
                                          withdraw the patent
                                          information and request that
                                          the patent information be
                                          removed from the list.
                                          If the NDA holder is
                                          required by court order to
                                          amend patent information or
                                          withdraw a patent from the
                                          list, it must submit a copy of
                                          the order to FDA (OGD Document
                                          Room, Attn: Orange Book Staff)
                                          within 14 days of order entry.
                                          FDA will remove a patent from
                                          the list if there is no first
                                          applicant eligible for 180-day
                                          exclusivity or upon the
                                          expiration of the 180-day
                                          period.
                                          If the term of a
                                          listed patent is extended
                                          under 35 U.S.C. 156(e), the
                                          NDA holder must submit on Form
                                          FDA 3542 a correction to the
                                          patent expiration date within
                                          30 days of receipt of a
                                          certificate of extension or
                                          documentation of an extension
                                          of the patent term.
                                          Corrections or changes
                                          to previously submitted patent
                                          information, other than
                                          withdrawal of a patent and
                                          requests to remove a patent
                                          from the list (delisting
                                          requests), must be submitted
                                          on Form FDA 3542 or 3542a, as
                                          appropriate.
                                          Withdrawal of a patent
                                          and delisting requests must be
                                          submitted as described in Sec.
                                            314.53(d)(4), except it need
                                          not be submitted on Form FDA
                                          3542. The patent withdrawal
                                          and delisting request must
                                          contain the NDA number, each
                                          product to which the request
                                          applies, and the patent
                                          number.
------------------------------------------------------------------------
\1\ These highlights describe important proposed revisions to our
  regulations, but should not be relied upon in place of the proposed
  regulation.

    II.B.4.a. Requests by persons other than the NDA holder--patents
that claim an approved method of using the drug product (proposed Sec.
314.53(f)(1)). To efficiently implement the statutory provisions in
section 505(b)(2)(B) and (j)(2)(C)(viii) of the FD&C Act, we are
proposing to enhance the mechanism for challenging the accuracy or
relevance of information with respect to method-of-use patents
submitted to the Agency under Sec.  314.53 and listed in the Orange
Book.
    In the preamble to the June 2003 final rule on patent submission
and listing requirements, we discussed our longstanding position,
codified in Sec.  314.53(b) and (c)(2), that ``only method-of-use
patents that claim a use of the drug product in the pending or approved
application must be submitted'' (68 FR 36676 at 36681). The June 2003
final rule further explained: ``The declarant must describe each
individual method of use for which a patent is submitted for listing,
and identify the corresponding language found in the labeling of the
approved NDA that corresponds to that method of use. This information
will expedite our review of ANDA and 505(b)(2) applications that do not
seek approval for all the approved uses. In determining whether an ANDA
applicant can `carve out' the method of use, rather than certify to the
listed patent, we will rely on the description of the approved use
provided by the NDA holder or patent owner in the patent declaration
and listed in the Orange Book'' (68 FR 36676 at 36682).
    An NDA holder or patent owner must provide adequate information in
its submission of patent information to enable potential 505(b)(2) and
ANDA applicants to avail themselves of the statutory provision that
permits a 505(b)(2) or ANDA applicant to not certify to a patent by
stating that it is not seeking approval for the method of use claimed
by the listed patent (see section 505(b)(2)(B) and (j)(2)(C)(viii) of
the FD&C Act, respectively) and carving out from product labeling the
corresponding use information. Our July 2007 revision of Forms FDA
3542a and 3542 clarifies, in its instructions, that ``[t]he use code
designates a method of use patent that claims the approved indication
or use of a drug product. Each approved use claimed by the patent
should be separately identified in this section and contain adequate
information to assist 505(b)(2) and ANDA applicants in determining
whether a listed method of use patent claims a use for which the
505(b)(2) or ANDA applicant is not seeking approval'' (Form FDA 3542,
section 4.2b).
    Section 314.53(f) currently provides that, upon notification of the
grounds for a disagreement with the accuracy or relevance of the patent
submission, FDA will request that the NDA holder confirm the
correctness of the patent information or omission of patent
information. Proposed Sec.  314.53(f)(1) would establish a 30-day
timeframe in which the NDA holder is required to respond to FDA's
request in order to facilitate timely resolution of the patent listing
dispute.
    Proposed Sec.  314.53(f)(1) also would further specify that, in
response to notification of a patent listing dispute for a listed
patent that claims an approved method of using the drug product, FDA
will request that the NDA holder confirm the correctness of its
description of the approved indication or method of use that has been
included as the ``use code'' in the Orange Book, and provide
information on the specific approved use claimed by the patent that
enables the Agency to make a determination in accordance with section
505(b)(2)(B) or (j)(2)(C)(viii) of the FD&C Act. If the patent has been
listed and the NDA holder confirms the accuracy of the patent
information, fails to timely respond to FDA's request under Sec.
314.53(f), or submits a revision to the use code that does not provide
adequate clarity for FDA to determine whether the scope of the proposed
labeling carve-out would be appropriate based on the NDA holder's use
code and approved labeling, FDA is proposing to review a proposed
labeling carve-out(s) for the 505(b)(2) application or ANDA with
deference to the 505(b)(2) or ANDA applicant's interpretation of the
scope of the patent. In determining whether a proposed omission of use
information

from labeling is appropriate, the Agency will consider the use code and
labeling information submitted by the NDA holder on Form FDA 3542, the
history of labeling changes related to approval of an indication(s) for
the drug product, the 505(b)(2) or ANDA applicant's interpretation of
the scope of the patent, the need for consistent labeling among
products approved under section 505(j) of the FD&C Act, and the
requirements of Sec. Sec.  314.94(a)(8)(iv) and 314.127(a)(7), as
appropriate.
    The following hypothetical example illustrates our approach under
proposed Sec.  314.53(f)(1) to determining whether an ANDA applicant's
proposed labeling carve-out would be appropriate: The NDA holder
submits Form FDA 3542 to the Office of Generic Drugs, Document Room,
Attention: Orange Book Staff, within 30 days after issuance of the '321
patent claiming a method of using the drug product Gaindrolone. The NDA
holder provided the use code ``to promote weight gain after weight loss
in certain types of patients'' for each patent that it submitted for
listing in the Orange Book, but did not specifically identify the
approved use(s) (e.g., patient population(s)) claimed by the patent. In
section 4.2a of Form FDA 3542, the NDA holder further identified the
patented method of use claimed in patent claims 8, 9, and 10 of the
'321 patent with specific reference to the following sections of the
approved labeling for the drug product: Indications and Usage
(``indicated as adjunctive therapy to promote weight gain after weight
loss following extensive surgery, chronic infections, or severe
trauma'') and Dosage and Administration. Applicant A submits an ANDA
that cites Gaindrolone as the basis for ANDA submission and contains a
505(j)(2)(A)(viii) statement with respect to the '321 patent. Applicant
A also notifies the Agency in a written communication titled
``314.53(f) Patent Listing Dispute'' that the use code listed in the
Orange Book for the '321 patent is overbroad as Applicant A interprets
the scope of the '321 patent to be limited to ``adjunctive therapy to
promote weight gain after weight loss following chronic infections.''
Applicant A contends that other approved patient populations are not
within the scope of the '321 patent. FDA subsequently provides the NDA
holder with the Applicant A's basis for disagreement with the accuracy
of the listed patent information and requests that the NDA holder
confirm the correctness of the description of the specific approved use
claimed by the patent or revise the description within 30 days. The NDA
holder confirms the use code ``to promote weight gain after weight loss
in certain types of patients'' and thus does not provide adequate
clarity for the Agency to make a determination in accordance with
section 505(j)(2)(A)(viii) of the FD&C Act on whether Applicant A could
carve out the patented use in ``certain types of patients'' and seek
approval for the remaining uses. Accordingly, FDA reviews the proposed
ANDA labeling with deference to Applicant A's interpretation of the
scope of the patent and approves the ANDA for ``adjunctive therapy to
promote weight gain after weight loss following extensive surgery or
severe trauma.'' As noted in the June 2003 final rule, ``the claim-by-
claim listing of method-of-use patents will permit ANDA and 505(b)(2)
applicants to assess whether they are seeking approval for a use
claimed in the listed patent, and thus determine whether to submit a
patent certification or a section viii statement. Additionally, we
[FDA] can verify that the certification or statement is correct, and
that only the appropriate methods of use are included in the proposed
labeling for the ANDA or 505(b)(2) drug product'' (68 FR 36676 at
36685). Applicant A has a strong incentive to interpret the scope of
the patent correctly to avoid being subject to patent infringement
litigation following ANDA approval and potentially enjoined from
marketing its product. The use code submitted by the NDA holder remains
listed in the Orange Book (compare June 2003 final rule (68 FR 36676 at
36683) (``[u]se codes are intended to alert ANDA and 505(b)(2)
applicants to the existence of a patent that claims an approved use.
They are not meant to substitute for the applicant's review of the
patent and the approved labeling'').
    In the same example above, we note that if the NDA holder had
responded to FDA's request by revising the description of the specific
approved use claimed by the patent in a manner that provided sufficient
information for the Agency to make a determination in accordance with
section 505(j)(2)(A)(viii) of the FD&C Act on whether Applicant A could
carve out the patented use, FDA would have no occasion to review the
proposed ANDA labeling with deference to Applicant A's interpretation
of the scope of the patent. For example, if the NDA holder submitted a
revised Form 3542 that provided a revised use code (hypothetically ``to
promote weight gain after weight loss following chronic infections or
severe trauma'') and specifically referred to the corresponding portion
of the approved labeling, there would be sufficient information for the
Agency to make a determination in accordance with section
505(j)(2)(A)(viii) of the FD&C Act. Accordingly, there would be no
ambiguity that would warrant review of the proposed ANDA labeling with
deference to Applicant A's interpretation of the scope of the patent,
even if Applicant A's interpretation differed from that of the NDA
holder.
    As previously discussed in the June 2003 final rule, we reiterate
that the Agency's role in patent listing is ministerial and does not
involve substantive review of patents (see 68 FR 36676 at 36683).
Rather, our proposed revisions to the regulations in 314.53(f) are
intended to provide the Agency with the information necessary to
implement section 505(b)(2)(B) and (j)(2)(C)(viii) of the FD&C Act. FDA
believes that enhancing the mechanism for challenging overbroad use
codes listed in the Orange Book may cause NDA holders to be more
circumspect in their original submission of patent information to FDA.
Accordingly, we expect that there will rarely be a need for the Agency
to review the proposed labeling for the 505(b)(2) application or ANDA
with deference to the 505(b)(2) or ANDA applicant's interpretation of
the scope of the patent. However, we invite comment on this proposed
approach to enhancing FDA's response to challenges to the accuracy or
relevance of submissions of patent information to the Agency, while
maintaining the Agency's ministerial role in patent listing.
II.B.4.b. Requests by NDA Holder To Remove Patent Information From the
List (Proposed Sec.  314.53(f)(2))
    II.B.4.b.i. Patents or patent claims that no longer meet the
statutory requirements for listing. Section 1102(a)(2) of the MMA
amends section 505(j)(5)(D)(i)(I) of the FD&C Act to define certain
events that constitute forfeiture of 180-day exclusivity. As noted in
section I, we are implementing the 180-day exclusivity provisions of
the MMA directly from the statute and will determine if additional
rulemaking is necessary in the future. Where a novel issue of
interpretation is raised by a particular factual scenario regarding
forfeiture of 180-day exclusivity, we may open a public docket or
otherwise seek comment from affected parties in advance of taking
action (see section I.D). However, we are proposing at this time to add
Sec.  314.53(f)(2) regarding requests by an NDA holder to remove patent
information from the list to implement section
505(j)(5)(D)(i)(I)(bb)(CC) of the FD&C

Act (forfeiture of 180-day exclusivity due to failure to market where
the patent or patent information that qualified the first applicant for
180-day exclusivity is withdrawn by the NDA holder), and to clarify our
current practice with respect to withdrawal of a patent or patent
information by an NDA holder.
    Under proposed Sec.  314.53(f)(2), if the NDA holder determines
that a patent or patent claim (e.g., a method-of-use claim) no longer
meets the statutory requirements for listing, the NDA holder is
required to promptly notify FDA to withdraw the patent or patent
information and request that the patent or patent information be
removed from the list. Circumstances under which a patent or patent
claim no longer meets the statutory requirements for listing include,
but are not limited to, a judicial finding of invalidity or
unenforceability for a listed patent, from which no appeal has been or
can be taken, or a court order to amend patent information or withdraw
a patent from the list. We note that an NDA applicant that determined
that a patent or patent claim submitted on Form FDA 3542a no longer met
the statutory requirements for listing prior to NDA approval would
``withdraw'' the patent or patent claim by not including the patent or
patent claim in its submission of Form FDA 3542 upon approval of the
NDA or NDA supplement. There is no need to submit a request to remove
the patent or patent claim from the list because such patent
information is listed in the Orange Book only upon approval of the NDA
or NDA supplement.
    The FD&C Act does not provide an independent cause of action for a
505(b)(2) or ANDA applicant seeking an order requiring an NDA holder to
correct or delete patent information listed in the Orange Book (see
section 505(c)(3)(D)(ii)(II) and (j)(5)(C)(ii)(II) of the FD&C Act; see
also Mylan Pharmaceuticals, Inc. v. Thompson, 268 F.3d 1323 (Fed. Cir.
2001) (holding that the pre-MMA statutory scheme did not recognize a
cause of action for delisting a patent from the Orange Book, and that
``such an action would be a private right of action barred by the
[act]'')). If a 505(b)(2) or ANDA applicant successfully asserts a
counterclaim to a patent infringement action to obtain an order
requiring the NDA holder to amend or withdraw patent information from
the list (see section 505(c)(3)(D)(ii)(I) and (j)(5)(C)(ii)(I) of the
FD&C Act), the NDA holder must withdraw the patent or patent
information and request that the patent or patent information be
removed from the list. The Agency will not remove the patent or patent
information in response to a request, accompanied by a copy of the
court order, from the 505(b)(2) or ANDA applicant or on its own. We are
proposing to require an NDA holder to submit a copy of a court order
requiring amendment or withdrawal of patent information to the Orange
Book Staff through the Office of Generic Drugs Document Room within 14
calendar days of the date on which the order was entered. By providing
a 14-day timeframe within which an NDA holder must notify FDA of this
type of court order, the proposed regulation would facilitate the NDA
holder's compliance with obligations under the FD&C Act and applicable
regulations and ensure that pending 505(b)(2) applications or ANDAs
that have provided a patent certification to the amended or withdrawn
patent are not inappropriately delayed if they are otherwise eligible
for approval. The Orange Book Staff subsequently will forward a copy of
the court order to the NDA through the CDER Central Document Room.
    We recognize that for patents that meet the statutory criteria for
listing in the Orange Book, fewer than all of the patent claims may be
the subject of litigation against a particular 505(b)(2) or ANDA
applicant. In such a case, a judicial finding of invalidity for certain
patent claims and withdrawal of that patent information by submission
of an amended Form FDA 3542 may not necessarily be reflected in the
Orange Book (unless, for example, all drug product claims were
invalidated and only a method-of-use claim remained). Accordingly, it
would be prudent for current and prospective 505(b)(2) and ANDA
applicants to be aware of relevant court decisions in patent litigation
(see also the 1994 final rule (59 FR 50338 at 50346) (noting the
prudence of conducting patent searches to identify patents that may be
ineligible for listing in the Orange Book but that may be infringed by
a proposed product)).
    Consistent with our current practice, proposed Sec.  314.53(f)(2)
states that we will remove a patent from the Orange Book when the NDA
holder has informed us that the patent no longer meets the statutory
requirements for listing if there is no first applicant eligible for
180-day exclusivity or upon the expiration of the 180-day exclusivity
period of a first applicant.
    Proposed Sec.  314.53(f)(2) also applies to amendment of the patent
information to remove a claim (drug substance, drug product, or method
of use) from the list. For example, if a patent is listed in the Orange
Book as claiming the drug product and a method of use, and an NDA
holder withdrew only the drug product claim and requested that the drug
product claim be removed from the list, we would remove the drug
product claim from the Orange Book if there is no first applicant
eligible for 180-day exclusivity or upon the expiration of the 180-day
exclusivity period of a first applicant. This provision is intended to
address scenarios in which an ANDA applicant has submitted a paragraph
IV certification with respect to the drug substance or drug product
claim and a 505(j)(2)(C)(viii) statement with respect to a method-of-
use claim for a single patent.
    When an NDA holder has withdrawn a patent and submitted to FDA a
request to remove the patent from the Orange Book, we currently
identify this request in a separate column in the Orange Book titled
``Delist Requested.'' If an NDA holder withdraws a patent claim (e.g.,
a method-of-use claim in a patent that also claims the drug product)
and submits to FDA a request to remove the patent claim from the Orange
Book, we intend to identify this request with a symbol (e.g., an
asterisk) in the column for that claim. These notations signal that the
patent or patent claim remains listed in the Orange Book only to
preserve a first applicant's eligibility for 180-day exclusivity for
their pending ANDA or during the period of 180-day exclusivity after
approval of the first applicant's ANDA. While the patent or patent
claims remain listed in the Orange Book, subsequent ANDA applicants
must submit or maintain an appropriate patent certification or
statement with respect to the patent or patent claims for which the
delisting request has been submitted. This requirement is consistent
with preservation of a first applicant's eligibility for 180-day
exclusivity because the 180-day exclusivity period bars approval of
subsequent ANDAs for the same drug product that also contain a
paragraph IV certification to the patent (see section
505(j)(5)(B)(iv)(I) of the FD&C Act). However, a 505(b)(2) applicant is
not required to certify or maintain a previous certification to the
patent for which a request to remove the patent from the list has been
submitted, because such a patent remains listed in the Orange Book only
for purposes of preserving a first ANDA applicant's eligibility for
180-day exclusivity.
    An applicant can determine that a patent or patent claim has been
removed from the Orange Book if it no longer appears in the Orange Book
patent listings for the drug product at issue. In addition, FDA
maintains a separate Web page linked from the ``search by patent''

option on the Orange Book Web page that identifies patents that have
been recently delisted (currently located at http://www.accessdata.fda.gov/scripts/cder/ob/docs/delist.cfm).
    II.B.4.b.ii. Patent term restoration. Proposed Sec.
314.53(f)(2)(ii) directs NDA holders to submit a correction to the
expiration date of their listed patent if the term of the patent is
extended under the patent term restoration provisions of 35 U.S.C. 156,
and sets a timeframe for compliance. With respect to patents eligible
for listing in the Orange Book, the Hatch-Waxman Amendments generally
provide that the terms of certain patents may be extended for a period
of up to 5 years if the patent claims a product or method of using a
product that has been subject to a defined regulatory review period
before commercial marketing or use (see 35 U.S.C. 156(a)). We are
proposing to require the NDA holder to submit the correction to the
patent expiration date on Form FDA 3542 within 30 calendar days of
receipt of a certificate of extension as described in 35 U.S.C.
156(e)(1) or documentation of an extension of the term of the patent as
described in 35 U.S.C. 156(e)(2). The 30-day timeframe within which an
NDA holder must notify FDA of the patent term extension is consistent
with the statutory timeframe set forth in section 505(c)(2) of the FD&C
Act for filing with FDA the patent number and patent expiration date of
any patent that claims the drug or method of using the drug and is
issued after NDA approval. Although extension of the patent term of a
previously issued patent is not explicitly within the scope of section
505(c)(2) of the FD&C Act, the proposed 30-day timeframe for submission
of a correction of the patent expiration date is consistent with the
objective of ensuring that prospective 505(b)(2) and ANDA applicants
have timely notice of changes to the asserted patent coverage for a
listed drug.
    II.B.4.b.iii. Submissions to FDA. Proposed Sec.  314.53(f)(2)(iii)
would require that corrections or changes to previously submitted
patent information (other than withdrawal of a patent or requests to
remove a patent from the list) must be submitted on Form FDA 3542a or
3542, as appropriate. This proposed requirement is intended to
facilitate listing of patent information in the Orange Book and ensure
that patent information is accompanied by the patent declaration
verification required by Sec.  314.53(c)(2)(i)(Q) and (c)(2)(ii)(R) and
set forth in the certification requirements of Form FDA 3542a or 3542,
respectively. We note that we will not accept corrections or changes
that are not submitted on the appropriate forms. However, an NDA holder
may elect to submit a cover letter highlighting the corrections or
changes made in the accompanying Form FDA 3542. An NDA holder's
withdrawal of fewer than all of a previously submitted patent's claims
(e.g., withdrawal of the method of use claim(s) for a patent that also
claims the drug product) would be considered a correction or change to
patent information for purposes of proposed Sec.  314.53(f)(2)(iii)
because the patent would remain listed in the Orange Book.
    However, proposed Sec.  314.53(f)(2)(iv) clarifies that an NDA
holder's withdrawal of a patent and request to remove a patent from the
Orange Book is not required to be submitted on Form FDA 3542a (with
respect to pre-approval withdrawal of a patent) or FDA Form FDA 3542.
The withdrawal of a patent must be submitted as an amendment to the NDA
if the application has not been approved. After NDA approval, the
withdrawal of a patent must be submitted to the Orange Book Staff
through the OGD Document Room and must specify the patent number, the
application number, and each product(s) approved in the application to
which the request applies. The Orange Book Staff subsequently will
forward a copy of the patent withdrawal to the NDA through the CDER
Central Document Room.

II.C. Patent Certification (Proposed Sec. Sec.  314.50(i) and
314.94(a)(12))

II.C.1. Method-of-Use Patents (Proposed Sec. Sec.  314.50(i)(1)(iii)
and 314.94(a)(12)(iii))
    We are proposing to revise Sec. Sec.  314.50(i)(1)(iii) and
314.94(a)(12)(iii) to clarify that a 505(b)(2) or ANDA applicant that
is not seeking approval for any indications or other conditions of use
that are covered by a method-of-use patent for the listed drug(s)
relied upon or RLD, respectively, and has omitted corresponding
labeling from its proposed product may submit a statement under section
505(b)(2)(B) or 505(j)(2)(A)(viii), respectively, instead of a patent
certification with respect to any method-of-use claims. The proposed
addition of the phrase ``or other conditions of use'' to Sec. Sec.
314.50(i)(1)(iii) and 314.94(a)(12)(iii) reflects that a method-of-use
patent that claims a use other than an indication may be submitted for
listing in the Orange Book and may be the subject of a statement under
section 505(b)(2)(B) or 505(j)(2)(A)(viii) with an accompanying
labeling carve-out. This proposed revision is intended to conform with
current Agency practice.
II.C.2. Method-of-Manufacturing Patents (Proposed Deletion of
Sec. Sec.  314.50(i)(2) and 314.94(a)(12)(iv))
    The current regulations in Sec. Sec.  314.50(i)(2) and
314.94(a)(12)(iv) state that a 505(b)(2) or ANDA applicant,
respectively, is not required to make a patent certification with
respect to any patent that claims only a method of manufacturing the
drug product (method-of-manufacturing patent). This has been
incorrectly interpreted by certain applicants to mean that a
manufacturer could elect to submit such a patent for listing. In 2003,
Sec.  314.53(b) was amended to state, among other things, that process
patents (i.e., method-of-manufacturing patents) must not be submitted
to FDA (68 FR 36676 at 36679). Therefore, we are proposing that current
Sec. Sec.  314.50(i)(2) and 314.94(a)(12)(iv) be removed (and reserved)
to ensure consistency and clarity in our regulations.
II.C.3. Licensing Agreement (Proposed Sec.  314.50(i)(3))
    We are proposing to revise Sec.  314.50(i)(3) regarding licensing
agreements to remove the references to an ``immediate effective date''
and clarify that the patent owner with whom the applicant has a
licensing agreement may consent to approval of the 505(b)(2)
application (if otherwise justified) as of a specific date. These
proposed revisions reflect that there may be barriers to approval other
than the patent that is the subject of the licensing agreement. In
addition, the proposed revision acknowledges that a patent owner may
consent to approval as of a specific date.
    This proposed revision does not alter the current requirements for
a 505(b)(2) (or ANDA) applicant that submits a paragraph IV
certification to a patent that claims the listed drug relied upon and
for which the applicant has a licensing agreement with the patent owner
(see proposed Sec. Sec.  314.50(i)(3) and 314.94(a)(12)(v)). A
505(b)(2) or ANDA applicant must comply with the statutory requirements
for sending notice of paragraph IV certification under section
505(b)(3) and (j)(2)(B) of the FD&C Act, respectively, with respect to
each listed patent for which it has submitted a paragraph IV
certification notwithstanding the applicant's statement that it has
been granted a patent license.

II.D. Notice of Paragraph IV Certification (Proposed Sec. Sec.  314.52
and 314.95)

II.D.1. Timing of Notice
    A 505(b)(2) or ANDA applicant submitting a paragraph IV
certification is required to give notice of the patent challenge to the
holder of the NDA for the listed drug(s) relied upon or RLD,
respectively, and each owner of the patent that is the subject of the
certification within a specified timeframe (see section 505(b)(3) and
(j)(2)(B) of the FD&C Act). We are proposing to revise our regulations
to clearly delineate the two limitations on the timeframe within which
notice can be provided to the NDA holder and each patent owner of a
paragraph IV certification to a listed patent: (1) The date before
which notice may not be given and (2) the date by which notice must be
given. The MMA amended the FD&C Act to establish the date by which
notice of a paragraph IV certification must be given to the NDA holder
and each patent owner. Table 5 summarizes the proposed changes related
to the timing of providing notice of a paragraph IV certification.

  Table 5--Highlights of Proposed Changes Regarding Timing of Notice of
                     Paragraph IV Certification \1\
------------------------------------------------------------------------
                                                Proposed revisions to
            Current regulations                      regulations
------------------------------------------------------------------------
Sending the notice (Sec.  Sec.   314.52(b)  Sending the notice (Sec.
 and 314.95(b))                              Sec.   314.52(b)(1) and
                                             (b)(2) and 314.95(b)(1) and
                                             (b)(2))
 505(b)(2) applicant must send       Except as provided
 notice required by Sec.   314.52(a) when    in Sec.   314.52(d), a
 it receives from FDA an acknowledgment      505(b)(2) applicant must
 letter stating that its 505(b)(2)           send notice required by
 application has been filed.                 Sec.   314.52(a) on or
                                             after the date it receives
                                             from FDA a paragraph IV
                                             acknowledgment letter, but
                                             not later than 20 days
                                             after the date of the
                                             postmark on the paragraph
                                             IV acknowledgment letter.
                                             Any required notice
                                             is invalid if it is sent
                                             before the 505(b)(2)
                                             applicant's receipt of a
                                             paragraph IV acknowledgment
                                             letter. The applicant will
                                             not have complied with Sec.
                                               314.52(b) until it sends
                                             valid notice.
 ANDA applicant must send notice     Except as provided
 required by Sec.   314.95(a), when it       in Sec.   314.95(d), an
 receives from FDA an acknowledgment         ANDA applicant must send
 letter stating that its ANDA is             notice required by Sec.
 sufficiently complete to permit a           314.95(a) on or after the
 substantive review.                         date it receives from FDA
                                             an acknowledgment letter or
                                             a paragraph IV
                                             acknowledgment letter, but
                                             not later than 20 days
                                             after the date of the
                                             postmark on the
                                             acknowledgment letter or
                                             paragraph IV acknowledgment
                                             letter.
                                             Any required notice
                                             is invalid if it is sent
                                             before the ANDA applicant's
                                             receipt of an
                                             acknowledgment letter or a
                                             paragraph IV acknowledgment
                                             letter, or before the first
                                             working day after the day
                                             the patent is published in
                                             the list. The applicant
                                             will not have complied with
                                             Sec.   314.95(b) until it
                                             sends valid notice.
                                             The 20-day clock
                                             begins on the day after the
                                             date of the postmark on the
                                             paragraph IV acknowledgment
                                             letter. When the 20th day
                                             falls on Saturday, Sunday,
                                             or a Federal holiday, the
                                             20th day will be the next
                                             day that is not a Saturday,
                                             Sunday, or Federal holiday.
Sending the notice (Sec.  Sec.   314.52(b)  Sending the notice (Sec.
 and 314.95(b))                              Sec.   314.52(b)(3) and
                                             314.95(b)(3)
 At the same time, the 505(b)(2)     At the same time
 or ANDA applicant must amend its            the 505(b)(2) or ANDA
 application to include a statement          applicant sends the notice
 certifying that notice of paragraph IV      required by Sec.
 certification has been provided to each     314.52(a) or Sec.
 person identified under Sec.   314.52(a)    314.95(a), respectively, it
 or Sec.   314.95(a), respectively, and      must submit an amendment to
 that notice met the content requirement     its 505(b)(2) application
 under Sec.   314.52(c) or Sec.              that includes a statement
 314.95(c), respectively.                    certifying that the notice
                                             of paragraph IV
                                             certification has been
                                             provided to each person
                                             under Sec.   314.52(a) or
                                             Sec.   314.95(a),
                                             respectively, and that
                                             notice met the content
                                             requirement under Sec.
                                             314.52(c) or Sec.
                                             314.95(c), respectively.
------------------------------------------------------------------------
\1\ These highlights describe important proposed revisions to our
  regulations, but should not be relied upon in place of the proposed
  regulation.

    II.D.1.a. Date before which notice may not be given. We are
proposing to clarify the text of our regulations to reflect our
longstanding practice that notice of a paragraph IV certification may
not be sent by a 505(b)(2) or ANDA applicant unless and until we have
notified the applicant that its application has been filed or received,
as appropriate, in an acknowledgment letter or a paragraph IV
acknowledgment letter (see proposed Sec. Sec.  314.52(b)(1) and
314.95(b)(1)).
    Sections 314.52(b) and 314.95(b) currently require that a 505(b)(2)
and ANDA applicant, respectively, send notice of a paragraph IV
certification when it receives from FDA an acknowledgment letter
stating that the application is sufficiently complete to permit a
substantive review. An NDA, including a 505(b)(2) application, is
deemed sufficiently complete to permit a substantive review if it is
filed by the 60th day after submission (see Sec.  314.101(a)(1) and
proposed Sec.  314.101(a)(2)). An ANDA is received when FDA has made a
threshold determination that the ANDA is substantially complete and has
sent the ANDA applicant an acknowledgment letter or paragraph IV
acknowledgment letter (see Sec.  314.101(b)). We previously have
explained that notice of a paragraph IV certification is to be sent
only after the 505(b)(2) or ANDA applicant has received acknowledgment
from FDA that its application has been determined to be acceptable for
review because such notice subjects the 505(b)(2) or ANDA applicant to
the risk that it will be sued for patent infringement (see
``Abbreviated New Drug Application Regulations''; proposed rule (54 FR
28872; July 10, 1989) (1989 proposed rule); see also 35 U.S.C.
271(e)(2)). The receipt of notice of a paragraph IV certification by a
patent owner or the NDA holder (or their representatives) begins a 45-
day period within which the NDA holder or patent owner must initiate a
patent infringement action against the 505(b)(2) or ANDA applicant in
order to obtain, in certain cases, a statutory 30-month stay of
approval of the application while the patent infringement litigation is
pending (section 505(c)(3)(C) and (j)(5)(B)(iii) of the FD&C Act).
    The FD&C Act requires that a notice of paragraph IV certification
must state

that the 505(b)(2) application or ANDA containing the certification
``has been submitted'' (see section 505(b)(3)(D)(i) and
(j)(2)(B)(iv)(I) of the FD&C Act). As we noted in the preamble to the
1989 proposal to implement the Hatch-Waxman Amendments, however,
``[t]he statute and legislative history of Title I [of the Hatch-Waxman
Amendments] demonstrate that Congress did not intend incomplete
application submissions to trigger legal action by a patent owner or
approved application holder'' (1989 proposed rule, 54 FR 28872 at
28887). By requiring that a 505(b)(2) application has been filed or an
ANDA has been received before notice of a paragraph IV certification
can be given, we ensure that the NDA holder and patent owner do not
needlessly expend resources to initiate litigation with respect to an
application that is incomplete and therefore may not be reviewed by the
Agency (see 1989 proposed rule, 54 FR 28872 at 28887 and 1994 final
rule, 59 FR 50338 at 50349-50350). Accordingly, our current regulations
require that a 505(b)(2) or ANDA applicant's notice of a paragraph IV
certification must include a statement that FDA has filed the NDA (in
the case of a 505(b)(2) application) or has received the ANDA (see
Sec. Sec.  314.52(c)(1) and 314.95(c)(1)).
    Despite the language in our existing regulations and the preamble
to the 1989 proposed rule, we have continued to receive inquiries from
the public regarding whether notice of paragraph IV certification may
be sent before the filing of a 505(b)(2) application or receipt of an
ANDA. Some have expressed uncertainty after enactment of the MMA
because the FD&C Act requires that notice be sent ``not later than 20
days after the date of the postmark on the notice with which [FDA]
informs the applicant'' that its 505(b)(2) application or ANDA has been
filed, without explicitly establishing a date earlier than which notice
may not be provided (see section 505(b)(3)(B)(i) and (j)(2)(B)(ii)(I)
of the FD&C Act).
    We are proposing to amend Sec. Sec.  314.52(b) and 314.95(b) by
revising and redesignating the current text as paragraphs (b)(1) and
(b)(3) and adding a new paragraph (b)(2). Proposed Sec.  Sec.
314.52(b)(2) and 314.95(b)(2) state that any notice sent before the
receipt of an FDA acknowledgment letter or paragraph IV acknowledgment
letter is invalid (and thus does not trigger either the 45-day period
in which the NDA holder and each patent owner may initiate a patent
infringement action and obtain a 30-month stay or the beginning of any
related 30-month period) and will not be considered to comply with the
FD&C Act's notice requirement until valid notice is sent. We also are
proposing to revise Sec.  314.95(b)(2) to state that any notice sent
before the first working day after the day the patent is published in
the Orange Book (the list) is invalid and will not be considered to
comply with the FD&C Act's notice requirement (see discussion in
section II.D.1.b.ii).
    An applicant that prematurely sends notice of a paragraph IV
certification must resend notice within the required timeframe in order
to satisfy the notice requirement of the FD&C Act and, in the case of a
first applicant, qualify for 180-day exclusivity. To help ensure that
notices of paragraph IV certifications are not sent prematurely, we
also are proposing to amend Sec.  Sec.  314.52(c)(3) and 314.95(c)(3)
to require that each 505(b)(2) or ANDA applicant include, in any notice
of paragraph IV certification related to its application, a statement
that it has received an acknowledgment letter or paragraph IV
acknowledgment letter. We recognize that this proposed requirement may
have the effect of delaying the provision of notice of paragraph IV
certification by a 505(b)(2) applicant (but not an ANDA applicant) by
approximately 2 weeks after the 505(b)(2) application is filed, because
an NDA is considered filed 60 days after submission, but our proposed
definition of a ``paragraph IV acknowledgment letter'' for a 505(b)(2)
application is the filing communication that is generally mailed by the
74th day after the date of submission of the 505(b)(2) application in
accordance with the performance goal established under the current
reauthorization of the prescription drug user fee program in FDASIA
(see section II.D.3.b). We recognize that this would potentially delay
the initiation of patent infringement litigation by an NDA holder or
patent owner and any corresponding 30-month stay of approval of the
505(b)(2) application by approximately 2 weeks. We invite comment on
this approach to premature notice of a paragraph IV certification for a
505(b)(2) application, especially with respect to notice sent after a
505(b)(2) application is filed (60th day after submission) and before a
paragraph IV acknowledgment letter (generally sent by the 74th day
after submission) is received.
    There have been some instances in which an applicant seeks to
submit an amendment containing a paragraph IV certification to its
505(b)(2) application or ANDA prior to filing or receipt of the
application as described in Sec.  314.101(a) and (b), respectively, and
receipt of an acknowledgment letter or a paragraph IV acknowledgment
letter. For example, an applicant may seek to amend its ANDA to add a
new strength of the drug product (see Sec.  314.95(d)(3)). We are
proposing to revise Sec. Sec.  314.52(d)(2) and 314.95(d)(2) to clarify
that an applicant submitting an amendment containing a paragraph IV
certification must comply with the timeframes set forth in Sec. Sec.
314.52(b) and 314.95(b) and wait until it has received an
acknowledgment letter or a paragraph IV acknowledgment letter before
sending notice of its paragraph IV certification to the NDA holder and
each patent owner. This approach ensures that a notice of paragraph IV
certification is not sent before we have accepted for substantive
review the underlying application to which the notice relates (i.e.,
before we have filed the 505(b)(2) application or received the ANDA).
As one Federal district court observed in upholding FDA's
interpretation of the statute in this scenario, ``[i]f an ANDA
applicant could send Paragraph IV notice when amending an ANDA that has
not yet been accepted as received, the applicant could accelerate the
timing provisions and litigation process well beyond the framework that
Congress intended'' (SB Pharmco Puerto Rico, Inc. v. Mutual
Pharmaceutical Co., 552 F. Supp. 2d 500, 510 (E.D. Pa.), appeal
dismissed, 2008 U.S. App. LEXIS 27672 (Fed. Cir. 2008) (holding that
notice of a paragraph IV certification sent concurrent with submission
of an amendment to an ANDA that had not yet been accepted for filing
``was not valid or timely'' under section 505(j)(2)(B)(ii)(II) of the
FD&C Act)).
    Thus, if an ANDA applicant submits an amendment containing a
paragraph IV certification before it has received an acknowledgment
letter or a paragraph IV acknowledgment letter advising that the ANDA
has been received for substantive review, the applicant is required to
send notice of its paragraph IV certification within 20 days after the
date of the postmark on the acknowledgment letter or paragraph IV
acknowledgment letter, as applicable. It is important to note that the
relevant date for purposes of determining first applicant eligibility
for 180-day exclusivity based upon submission of a paragraph IV
certification contained in an amendment is the date of submission of
the amendment (i.e., the date on which the amendment was officially
received (date-stamped) by the OGD Document Room) even though the
acknowledgment letter or paragraph IV acknowledgment letter may state
that the ANDA was received for substantive review on the date on which
the original ANDA was submitted (i.e., the date on

which the ANDA was officially received (date-stamped) by the OGD
Document Room) or, in the case of an ANDA that OGD initially refused to
receive under Sec.  314.101(d) or (e), the date on which the
deficiencies were resolved.
    II.D.1.b. Date by which notice must be given. The MMA amended the
FD&C Act to require that 505(b)(2) and ANDA applicants provide notice
of a paragraph IV certification to the NDA holder and each patent owner
in accordance with the following timeframes:
     If the paragraph IV certification is included in an
original 505(b)(2) application or ANDA, or in an amendment to such
application that is submitted before the applicant receives an
acknowledgment letter or paragraph IV acknowledgment letter, not later
than 20 days after the date of the postmark on the notice from FDA
informing the applicant that its application has been filed or received
(see section 505(b)(3)(B)(i) and (j)(2)(B)(ii)(I) of the FD&C Act), or
     If the paragraph IV certification is included in any other
amendment or in a supplement, at the time the applicant submits the
amendment or supplement (see section 505(b)(3)(B)(ii) and
505(j)(2)(B)(ii)(II) of the FD&C Act).
    II.D.1.b.i. Determining the timeframe for sending notice after
receipt of an acknowledgment letter or a paragraph IV acknowledgment
letter. We are proposing to revise Sec. Sec.  314.52(b)(1) and
314.95(b)(1) to require that an applicant must send notice of a
paragraph IV certification contained in a 505(b)(2) application or ANDA
on or after the date on which it receives an acknowledgment letter or a
paragraph IV acknowledgment letter, but not later than 20 days after
the date of the ``postmark'' (see proposed definition below) on the
acknowledgment letter or paragraph IV acknowledgment letter. As
discussed in sections II.A.2.u and II.A.2.y, we are proposing a broader
definition of the term ``postmark'' and, as applied to paragraph IV
acknowledgment letters for 505(b)(2) applications, an alternate
interpretation of the term ``postmark'' to reflect current OND practice
regarding the mailing of filing communications. For purposes of
proposed Sec.  314.52(b) and (c) only, the ``date of the postmark'' on
the paragraph IV acknowledgment letter for a 505(b)(2) application is
considered to be 4 calendar days after the date on which the filing
communication is signed by the signatory authority (generally the
Division Director or designee in OND) unless OND sends the filing
communication to the applicant via electronic transmission. If OND
sends the filing communication via electronic transmission, then our
proposed definition of ``postmark'' in Sec.  314.3(b) would apply. We
recognize that issuance of the filing communication within 14 days
after the 60-day filing date described in Sec.  314.101(a)(1) and
(a)(2) represents a performance goal under the current reauthorization
of the prescription drug user fee program in FDASIA. Accordingly, an
applicant that has submitted a 505(b)(2) application containing a
paragraph IV certification and has received neither a refuse-to-file
letter within 60 days nor a filing communication within 74 days after
FDA receives the 505(b)(2) application should contact FDA to request
issuance of the filing communication. We invite comment on whether an
alternate approach should be taken. With reference to an acknowledgment
letter or a paragraph IV acknowledgment letter for an ANDA, we
recognize that there may be scenarios in which the postmark on the
envelope containing an acknowledgment letter or a paragraph IV
acknowledgment letter is illegible or inadvertently absent. We invite
comment on the interpretation of the term ``postmark'' in the context
of an acknowledgment letter or a paragraph IV acknowledgment letter for
a 505(b)(2) application or an ANDA, and whether our regulations should
be amended to define differently the specific date on which the 20-day
notice period begins.
    The MMA does not specify how the 20-day period for providing notice
of a paragraph IV certification is to be calculated. We are proposing
in Sec. Sec.  314.52(b)(1) and 314.95(b)(1) to calculate this notice
period in the same way that we calculate the 45-day period within which
each patent owner and NDA holder may initiate a patent infringement
action (which may, if other applicable requirements are satisfied,
trigger a 30-month stay of approval of a 505(b)(2) application or ANDA)
following receipt of notice of a paragraph IV certification (see Sec.
314.107(f)). Specifically, we propose that the first day of the 20-day
period begin on the day after the date of the postmark on the
acknowledgment letter or paragraph IV acknowledgment letter. The 20-day
period is proposed to include all calendar days, except that if the
20th day falls on a Saturday, Sunday, or Federal holiday, the last day
of the 20-day period will be considered to be the next day that is not
a Saturday, Sunday, or Federal holiday. This approach reflects the most
conservative interpretation of the statute and is the calculation
method currently used by most ANDA applicants.
    There will be no regulatory benefit or consequence for applicants
based on when they provide notice of a paragraph IV certification
contained in an original application, as long as notice is provided
within the 20-day timeframe required by the MMA. An ANDA applicant that
does not comply with the statutory timeframe in section
505(j)(2)(B)(ii)(I) and (j)(2)(B)(ii)(II) of the FD&C Act for providing
notice of its paragraph IV certification will be subject to
administrative consequences (see section II.D.5).
    II.D.1.b.ii. Determining the timeframe for sending notice of a
paragraph IV certification upon submission of an amendment or
supplement. We are proposing to revise Sec. Sec.  314.52(d) and
314.95(d) to implement section 505(b)(3)(B)(i), (b)(3)(B)(ii),
(j)(2)(B)(ii)(I), and (j)(2)(B)(ii)(II) of the FD&C Act and for the
efficient enforcement of the FD&C Act. Our proposed revisions clarify
the applicable timeframe in which a 505(b)(2) or ANDA applicant must
send notice of a paragraph IV certification submitted in an amendment
or supplement to its 505(b)(2) application or ANDA, respectively. We
are proposing to revise and redesignate the current text of Sec. Sec.
314.52(d) and 314.95(d) as paragraph (d)(1) to accommodate the proposed
inclusion of additional paragraphs to Sec. Sec.  314.52(d) and
314.95(d). Table 6 summarizes the proposed changes related to the
timing of providing notice of paragraph IV certification(s) submitted
in an amendment or supplement to a 505(b)(2) application or ANDA.

  Table 6--Highlights of Proposed Changes Regarding Timing of Notice of
      Paragraph IV Certification in an Amendment or Supplement \1\
------------------------------------------------------------------------
                                                Proposed revisions to
            Current regulations                      regulations
------------------------------------------------------------------------
Amendment to an application or an           Amendment or supplement to a
 abbreviated application (Sec.  Sec.         505(b)(2) application or an
 314.52(d) and 314.95(d))                    ANDA (Sec.  Sec.
                                             314.52(d)(1) and
                                             314.95(d)(1))

 If an application or abbreviated   After receipt of an
 application is amended to include the       acknowledgment letter or
 certification described in Sec.  Sec.       paragraph IV acknowledgment