CENTER FOR DRUG EVALUATION AND
`
`‘
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-044
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`'
`
`DOCUMENTS
`
`

`

`ACTION PACKAGE CHECKLIST
`
`
` 4A # BLA STN#
`
`
`NDA # 22-044
`NDA Supplement # N/A
`
` If NDA, Efficacy Supplement Type N/A
`
`Applicant: Merck & Co., Inc.
`
`Janumet
`Proprietary Name:
`Established Name: sitagliptin/metformin HCl
`Dosage Form:
`Tablet
`-
`
`RPM: Lina AlJuburi, Pharm.D, M.S.
`
`Division: 510
`
`Phone #' 301-796-1168
`
`NDAs:
`NDA Application Type: E] 505(b)(l) X 505(b)(2)
`Efficacy Supplement:
`E] 505(b)(l) E] 505(b)(2)
`
`
`
`505(b)(2) NDAs and 505(b)(2) NDA supplements:
`Listeddrug(s) referred to in 505(b)(2) application (NDA #(s), Drug
`name(s)):
`
`
`
`
`of whether the original NDA was a (b)(l) or _a (b)(2)L
`Consult page 1 of the NDA Regulatory Filing Review for
`this application or Appendix A to this Action Package
`Checklist.)
`
`Provide a brief explanation of how this product is different from the
`listed drug.
`Fixed-dose combination of sitagliptin and metformin HCl
`
`
` NDA 20-357 Glucophage (metformin HCI) Tablets (A supplement can be either a (b)(l) or a (b)(2) regardless
`
`
`
`
` [:1 If no listed drug, check here and explain:
`
`
`
`
`N2 User Fee Goal Date
`4° Action Goal Date (if different)
`
`Review and confirm the information previously provided in
`Appendix B to the Regulatory Filing Review. Use this Checklist to
`update any information (including patent certification
`information) that is no longer correct.
`
`
` X Confirmed
`
`
`El Corrected
`Date: March 5, 2007
`
`
`March 3 l, 2007
`'9
`March 30, 2007
`
`”AB
`1:] NA I:IEICR
`
`Previous actions (specifiz type and datefor each action taken)
`
`'
`
`'1' Advertising (approvals only)
`Note: If accelerated approval (21 CFR 314.510/601.4l), advertising must have been
`submitted and reviewed (indicate dates ofreviews)
`
`X Requestedin AP letter
`E] Received and reviewed
`'
`
`Version: 7/12/06
`
`

`

`
`
`Page 2
`
`Application Characteristics
`
`9 v
`
`W W WRevieWpEiEr’i—ty? W X Standard [:1 prion?” W
`Chemical classification (new NDAs only):
`4
`
`NDAs, BLAs and Supplements:
`1:] Fast Track
`E] Rolling Review
`E] CMA Pilot 1
`E] CMA Pilot2
`
`1:] Orphan drug designation
`
`NDAs: Subpart H
`El Accelerated approval (21 CFR 314.510)
`[:1 Restricted distribution (21 CFR 314.520)
`Subpart l
`y
`E] Approval based on animal studies
`
`BLAs: Subpart E
`E] Accelerated approval (21 CFR 601.41)
`El Restricted distribution (21 CFR 601.42)
`Subpart H
`E] Approval based on animal studies
`
`». .,
`
`NDAs and NDA Supplements:
`[:1 OTC drug
`
`Other:
`
`Other comments:
`
`o
`
`This application is on the AIP
`
`0
`
`0
`
`Exception for review file Center Director’s memo in Administrative
`Documents section)
`
`OC clearance for approval Oile communication in Administrative
`Documents section)
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`
`Indicate what types (if any) of information dissemination are anticipated
`
`1:] FDA Press Release
`1:] FDA Talk Paper
`E] CDER Q&As
`
`[:1 Other
`
`Version: 7/12/2006
`
`

`

`X Included
`
`Page 3
`
`o v
`
`Exclusivity
`o Nlesi Exclusivity Suinmary (approvals only) mlejsamm—aryin Administrative _
`Documents section)
`
`
`C] Yes
`X No
`If, yes, NDA/BLA #
`date exclusivity expires:
`
`and
`
`[:IYes
`VXNo
`If yes, NDA #
`and date
`exclusivity expires:
`
`El Yes
`X No
`If yes, NDA #
`and date
`exclusivity expires:
`
`I:I Yes
`X No
`If yes, NDA #
`and date
`exclusivity expires:
`
`1:] Verified
`
`X Verified
`
`[:1 Not applicable because drug is
`an old antibiotic.
`
`21 ‘crii 3’1zil"30(i)(1)‘(i)(A5‘
`X Verified
`
`21 CFR 314.50(i)(1)
`El (ii) Cl (iii)
`E] No paragraph III certification _:
`Date patent will expire
`
`‘
`
`_l:l fi/A (no-pamgmph [V certification)
`
`0 * Is approval of this application blocked by any type of exbhis—ivit—y?
`
`-
`
`Is there existing orphan drug exclusivity for the “same” drug
`o NDAs/BLAs:
`or biologic for the proposed indication(s)? Refer to 21 CFR 316.3(b)(13) for
`the definition of "same drug "for an orphan drug (1e, active moiety). This
`definition is NOTthe same as that usedfor NDA chemical classification.
`
`0 NDAS: Is there remaining 5-year exclusivity that would bar effective
`approval of a 505(b)(2) application? (Note that, even ifexclusivity remains,
`the application may be tentatively approved ifit is otherwise readyfor
`approval.)
`
`0
`
`0
`
`Is there remaining 3-year exclusivity that would bar effective
`NDAS:
`approval of a 505(b)(2) application? (Note that, even ifexclusivity remains,
`the application may be tentatively approved if it is otherwise reaayfor
`approval.)
`
`Is there remaining 6-month pediatric exclusivity that would bar
`NDAS:
`effective approval of a 505(b)(2) application? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ifit is otherwise reaafv
`for approval.)
`
`Patent Information (NDAs and NDA supplements only)
`
`0
`
`Patent Information:
`
`0 v
`
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`If the drug is an old antibiotic, skip the Patent \
`Certification questions.
`
`0
`
`Patent Certification [505(b)(2) applications]:
`Verify that a certification was submitted for each patent for the listed drug(s) in
`the Orange Book and identify the type of certification submitted for each patent,
`
`' 0
`
`[505(b)(2) applications] If the application includesa paragraph III certification,
`it cannot be approved until the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`0
`
`o
`
`[505(b)(2) applications] For each paragraph IV certification, verify that the
`applicant notified the NDA holder and patent owner(s) of its certification that the
`patent(s) is invalid, unenforceable, or will not be infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Ifthe application does not include
`any paragraph IV certifications, mark “N/A " and skip to the next section below
`(Summary Reviews)).
`'
`
`[505(b)(2) applications] For each paragraph IV certification, based on the
`questions below, determine whether a 30-month stay of approval is in effect due
`to patent infringement litigation.
`
`Answer the following questions for each paragraph IV certification:
`
`(1) Have 45 days passed since the patent owner’s receipt of the applicant’s
`
`- Version: 7/12/2006
`
`

`

`Page 4
`
`notice of certification?
`
`(Note: The date that the patent owner received the applicant‘s notice of
`certification can be determined by checking the application. The applicant
`is required to amend its 505(b)(2) application to include documentation of
`this date (e.g., copy of return receipt or letter from recipient
`acknowledging its receipt of the notice) (see 21 CFR 314.52(e))).
`
`If “Yes, ” skip to question (4) below. If “No, " continue with question (2).
`
`(2) Has the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submitted a written waiver of its right to file a legal action for patent
`infringement after receiving the applicant’s notice of certification, as
`provided for by 21 CFR 314.107(t)(3)?
`
`ELYes
`
`If “ Yes, ” there is no stay ofapproval based on this certification. Analyze the next
`paragraph IV certification in the application, ifany. Ifthere are no other
`‘0
`paragraph IV certifications, skip to the next section below (Summary Reviews).
`
`If “No, ” continue with question (3).
`
`(3) Has the patent owner, its representative, or the exclusive patent licensee
`filed a lawsuit for patent infringement against the applicant?
`
`D Yes
`
`,
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(t)(2))).
`
`If “No, " the patent owner (or NDA holder, ifit is an exclusive patent licensee)
`has until the expiration ofthe 45-day period described in question (I) to waive its
`right to bring a patent infringement action or to bring such an action. After the
`45-day period expires, continue with question (4) below.
`
`(4) Did the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submit a written waiver of its right to file a legal action for patent
`infringement within the 45-day period described in question (1), as
`provided for by 21 CFR 314.107(t)(3)? ‘
`
`E] Yes
`
`If "Yes, ” there is no stay ofapproval based on this certification. Analyze the next
`paragraph IV certification in the application, ifany. Ifthere are no other
`paragraph IV certifications, skip to the next section below (Summary Reviews).
`
`If “No, " continue with question (5).
`
`' (5) Did the patent owner, its representative, or the exclusive patent licensee
`bring suit against the (b)(2) applicant for patent infringement within 45
`days of the patent owner’s receipt of the applicant’s notice of
`certification?
`
`[:1 Yes
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(t)(2)). if no written notice appears in the
`NDA file, confirm with the ap .licant whether a lawsuit was commenced
`
`"
`Version: 7/12/2006
`
`

`

`Page 5
`within mall's-day period).
`
`If ”No, " there is no stay ofapproval based on this certification. Analyze the
`next paragraph IV certification in the application, ifany, Ifthere are no other
`paragraph IV certifications, skip'to the next section below (Summary
`Reviews).
`
`If “ Yes, " a stay ofapproval may be in eflect. To determine ifa 30-month stay
`is in eflect, consult with the Director, Division ofRegulatory Policy 11, Ofi‘ice
`ofRegulatory Policy (HF0—007) and attach a summary ofthe response.
`
`
`
`
`
`0.0 Summary Reviews (e.g., Office Director, Division Director) (indicate datefor each
`
`Leader: March 30, 2007
`review)
`-
`
`
`
`Divismn Director and Team
`
`
`
`
`
`
`
`
`_
`
`March 30, 2007
`
`
`
`
`
`
`
`
`
`February 5,2007
`
`51
`, .1
`
`l l3
`
`.
`
`0 v
`
`
`Package Insert
`0 Most recent division-proposed labeling (only if generated after latest applicant
`submission_ oflabeling).
`0 Most recent applicant-proposed labeling (only if subsequent division labeling
`does not show applicant version)
`0 Original applicant-proposed labeling
`
`
`May'31 2006
`
`NDA 21—995 Januvia (sitagliptin)
`NDA 20-357 Glucophage
`
`(metfonnin)
`
`
`
`
`
`
`Original applicant-proposed labeling
`
`Other relevant labeling (eg, most recent 31n class, class labeling), if applicable
`
`
`
`
`
`
`'3' Medication Guide
`
`
`
`
`
`0 Most recent division-proposed labeling (only if generated after latest applicant
`
`
`
`submission of labeling)
`
`
`0 Most recent applicant-proposed labeling (only if subsequent division labeling
`
`
`
`does not show applicant version)
`
`0 Original applicantiproposed labeling __
`
`
`Other relevant labeling (e.g., most recent 3 in class, class labeling)
`
`
`Labels (full color carton and immediate—container labels)
`o Most-recent division-proposed labels (only if generated after latest applicant
`submission)
`
`o
`
`Other relevant labeling (e.g., most recent 3 in class, class labeling), if applicable
`
`Patient Package Insert
`0 Most-recent division~proposed labeling (only if generated after latest applicant
`submission of labeling)
`0 Most recent applicant-proposed labeling (only if subsequent division labeling
`does not show applicant version)
`
` 0
`
`0 v
`
`0 Most recent applicant—proposed labeling
`
`version; 7/12/2006
`
`

`

`
`
`X DMETS March 15 and 29, 2007
`
`X DSRCS March 20 and 28, 2007
`w Labeling reviews and minutes of any labeling meetings (indicate dates ofreviews and
`
`
`meetings)
`X DDMAC March 9, 2007
`
`
`
`
`
`X SEALD 'March 30, 2007
`
`C] Other reviews
`.
`
`
`I] Memos of Mtgs no labeling.
`
`
`meetings held with the sponsor. All.
`labeling discussions conducted via
`
`email.
`
` Administrative Reviews (RPM Filing Review/Memo of Filing Meeting; ADRA) (indicate
`date ofeach review)
`
`
`
` NDA and NDA supplement approvals only: Exelusivity Summary (signed by Division
`Director)
`
`
`
`None needed
`
`
`Center Director’s Exception for'Review‘memo
`
`None needed
`If AP: 0C clearance for approval
`
`x included
`' Pediatric Page (all actions)
`
`6
`0.0 Debarment certification (original applications only): verified that qualifying language was
`
`-
`not used in certification and that certifications from foreign applicants are cosigned by
`X Verified, statement is acceptable
`
`
`U.S. agent. (Include certification.)
`
`
`
`v Postmarketing Commitment Studies
`0 Outgoing Agency request for post-marketing commitments (flocated elsewhere
`
`March 8’ 2007
`in Mgkage, state where located)_
`
`March 21, 2007
`Incoming submission documenting commitment
`.
`June 7 and July l7, 2006
`.
`.
`.
`.
`,
`Outgomg correspondence (letters mcludmg prev1ous act1on letters, emalls, faxes, telecoms) March 8 and 16, 2007
`lntemal memoranda, telecons, email, etc. —W
`'2‘
`Minutes of Meetings
`-
`Pre-Approval Safety Conference (indicate date; approvalsonly)
`«
`Not NME, none needed
`
`Pre-NDA/BLA meeting (indicate date)
`- D No mtg March 6,2006_
`'
`
`
`EOP2 meeting (indicate date)
`I
`E] No mtg December 15, 2004
`i
`'
`'
`Other (e.g., EOP2a, CMC pilot programs)
`'
`i
`‘
`_
`
`02° Advisory C_omrnittee Meeting
`o
`Da_te of Meeting
`o
`48-hour alert or minutes, if available
`
`December l8, 2006
`
`X Included
`
`»
`
`-
`
`'
`
`,
`
`03° AIP—related documents
`
`0
`-
`
`o
`
`‘
`
`_
`
`
`
`‘3' Federal Register Notices, DESI documents, NAS/NRC reports (if applicable)
`
`
`
`
`
`'1' CMC/Product review(s) (indicate datefor each review)
`' 03° Reviews by other discipline—sliiivisions/Centers reddested by CMC/Eodu'ctiieviewer
`.
`.
`.
`(indicate datefor each revtew)
`
`February 28 and March 4, 2007
`X N
`
`one
`
`o 0
`
`.. Environmental Assessment (check one) (original and supplemental applications)
`
`
` X Categorical Exclusion (indicate review date)(all original applications ando February 28 2007
`0 E] Review & FONSl (indicate date of review)
`
`
`,
`
`1 Version: 7/12/2006
`
`
`
` .u..~.—«~.-.-.-~
`
`

`

`l’age 7
`
`o D Review & Environmental Impact Statement (indicate date ofeach review)
`
`F
`- 4. NDAs: Microbiology reviews (sterility & apyrogenicity) (indicate date ofeach review)
`X Not a aren'teral roduct
`
`
` Date completed: January 24, 2007
`
`
`X Acceptable
`
`
`_ _ CI Withhold recommendation
`
`Facilities Review/Inspection
`
`Q *
`
`3 NDAs: Facilities inspections (include BER printout)
`
`
`9’.
`
`. BLAs: Facility—Related Documents
`0
`Facility review (indicate date(s))
`
`
`
`0
`Compliance Status Check (approvals only, bothoriginal and supplemental
`El Requested
`applications) (indicate date completed, must be within 60 days prior to AP)
`El Accepted
`
`E] Hold
`
`02° NDAs: Methods Validation
`E] Completed
`[:1 Requested
`El Not yet requested
`E] Not needed
`
`"‘
`
`March 1,2007
`
`
`
`
`
`
`
`[or each review)
`__
`* °1f Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`0:0 ECAC/CAC report/memo of meet1ng
`
`
`None
`
`X None requested
`“- Nonclinical inspection review Summary (DSI)
`
`
`
`
` C11n1cal rev1ew(_s) (indicate datefor each review) _ March 812007“
`
`'1' Financial Disclosure reviews(s) or location/date if addressed'1n another review
`
`X None
`
`—— X Not needed
`
`
`‘2' Safety Update review(s) (indicate location/date ifincorporated into another review)
` RMP review by OSE
`
`02° Risk Management Plan review(s) (including those by OSE) (indicate location/date if
`February 20, 2007
`
`incorporated into another review)
`0: Controlled Substance Staff review(s) and recommendation for scheduling (indicate date of
`x Not needed
`
`each review)
`
`El None requested
`fut" _ DSI Inspection Review Summary(ies) (include copies ofDSI letters to investigators)
`0
`Cl1n1cal Stud1es
`
`__ 0
`_Bioequivalence Studies_
`
`
`' None
`4;
`.0
`Clin Pharm Studies
`'1.
`.
`.
`.
`.
`.
`[3' None
`-
`4'2
`.,,.,
`Stat1st1cal Rev1ew(s) (indicate datefor each revtew)
`March 5 2007 (labeling only)
`g
`.
`.'
`
`.
`.
`.
`.
`.
`.
`E] None
`.,'.
`
`. February 22, 2007 Cl1n1cal Pharmacology rev1ew(s) (Indicate datefor each rewew)
`
`
`“I I M
`
`_
`
`Version: 7/12/2006
`
`

`

`Page 8
`
`'
`
`_
`
`Appendix A to Action Package Checklist
`
`_
`
`NDA or NDA supplemental application13 likely to be a 505(b)(2) application if:
`(1) It relies on published literature to meet any of the approval requirements, and the applicant does not have a written
`right of reference to the underlying data If published literature15 citedin the NDA but13 not necessary for
`‘
`' ,
`approval, the inclusion of such literature will not, in itself, make the application a 505(b)(2) application
`~-
`(2) Or it relies for approval on the Agency'8 previous findings of safety and efficacy for a listed drug product and the
`. applicant does not own or have right to referencethe data supporting that approval.
`-
`(3) Or it relies on what15 "generally known" or- "seientifically accepted" about a class of products to support the
`
`' ”" safety or effectiveness ofthe particular drug for which the applicantis seeking apprbval. (Note, however, thatthis
`does not mean any reference to general information or knowledge (e.g., about disease etiology, support for
`‘
`particular endpoints, methods of analysis) causes the application to be a 505(b)(2) application.)
`
`Types of products for which 505(b)(2) applications are likely to be submitted include: fixed-dose combination drug
`products (e.g., heart drug and diuretic (hydrochlorothiazide) combinations); OTC monograph deviations(see 21 CFR
`330.11); new dosage forms; new indications; and, new salts.
`
`An efficacy supplement can be either a (b)(l) or a (b)(2) regardless of whether the original NDA was a (b)(l) or a (b)(2).
`
`An efficacy supplement is a 505(b)(1) supplement if the supplement contains all of the information needed to support the -
`approval of the change proposed in the supplement. For example, if the supplemental application is for a new indication,
`the supplement is a 505(b)(l) if:
`( 1) The applicant has conducted its own studies to support the new indication (or otherwise owns or has right of
`reference to the data/studies).
`(2) And no additional information beyond what18 included1n the supplement or was embodied1n the finding of
`safety and effectiveness for the original application or previously approved supplements1s needed to support the
`change For example, this would likely be the case with respect to safety considerations if the dose(s) was/were ,
`the same as (or lower than) the original application.
`__
`(3) And all other “criteria” are met (e.g., the applicant owns or has right of reference to the data relied upon for
`?%
`approval of the supplement, the application does not rely for approval on published literature based on data to
`which the applicant does not have a right of reference).
`
`A
`
`"
`
`
`
`An efficacy supplement is a 505(b)(2) supplement if:
`(1) Approval of the change proposed in the supplemental application would require data beyond that needed to
`support our previous finding of safety and efficacy in the approval of the original application (or earlier
`supplement), and the applicant has not conducted all of its own studies for approval of the change, or obtained a
`right to reference studies it does not own. For example, if the change were for a new indication‘AND a higher
`dose, we would likely require clinical efficacy data and preclinical safety data to approve the higher dose. Ifthe
`applicant provided the effectiveness data, but had to rely on a different listed drug, or a new aspect of a previously
`cited listed drug, to support the safety of the new dose, the supplement would be a 505(b)(2).
`'
`(2) Or the applicant relies for approval of the supplement on published literature thatis based on data that the
`applicant does not own or have a right to reference. If published literature15 cited1n the supplement but13 not
`necessary for approval, the inclusion of such literature will not, in itself make the supplement a 505(b)(2)
`supplement.
`(3) Or the applicant1s relying upon any data they do not own or to which they do not have right of reference.
`
`-'-If you have questions about whether an application is a 505(b)(1) or 505(b)(2) application, consult with your ODE’s
`» Office of Regulatory Policy representative;
`
`Version: 7/12/2006
`
`

`

`.lANUMETTM (Sitagiiptin phosphate/metformin hydrochloride) Tablets
`NDA No 22-044
`
`Patent Certification undeer U.S.C. 505 b 2 A A Item 14
`
`‘O
`
`The NDA Applicant certifies that, in the opinion of the NDA Applicant and to the
`best of the NDA Applicant’s knowledge, no patent information has been filed for a patent
`claiming the drug or a use of the drug for which investigations were conducted by or for
`someone other than NDA Applicant, for which NDA Applicant does not have a right of
`reference, and for'which information is required to be filed under section 505(b)(l) or
`505(c).
`.
`.
`
`Date Signed:
`
`#0? /'0/ 2005
`
`Authim'zcd Signature of'NDA Applicant:
`
`% 2' Mb
`
`Philippe L. Durette
`
`NDA Applicant’s Attorney
`Merck & Co., Inc.
`PO. Box 2000, RY 60—30
`
`Rahway, NJ 07065-0907
`Telephone Number: (732)-594~4568
`FAX Number: (732)694-4720
`E-Mail Address: phil_durette@mercl<.com
`
`
`
`Appears This Way
`On Original
`
`

`

`Department of Health and Human Services
`Food and Drug Administration
`
`Form ApprovedzoMB N?)3091043513
`BMW" Da'e‘ °
`"06
`
`PATENT INFORMATION SUBMITTED WITH THE FILING
`OF AN NDA, AMENDMENT, 0R SUPPLEMENT
`
`~
`
`”DA NUMBER
`224144
`
`For Each Patent That Claims a Drug Substance
`(Active Ingredient), Drug Product (Formulation and
`Composition) and/or Method of Use
`
`NAME OF APPLICANT I NDA HOLDER
`MERCK & 00.. NC.
`
`The following ls provided in accordance with Section 505(b) and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`JANUMETWI
`
`ACTIVE iNGREDiENTtS)
`Sliagliptin phosphate/Metformin hydrochloride
`
`STRENGTH(S)
`Sitagliptin phosphate/mefiormin hydrochloride
`
`DOSAGE FORM
`Tablets
`
`This patent declaration form Is required to be submitted to the Food and Drug Administration (FDA) with an NBA application.
`amendment. or supplement as required by 21 CFR 31453 at the address provided in 21 CFR 314 53(d)(4) Within thirty (30) days
`after approval of an NBA or supplement, or within thirty (30) days of issuance of a new patents a new patent declaration must be
`submitted pursuant to 21 CFR 3l4 53(c)(2)(il) with all of the required intonnalion based on the approved NDA or supplement. The
`information submitted in the declaration form submitted upon or after approval will be the only information relied upon by the FDA
`for listin- a natent in the Drama Book
`If additional space is required for any narrative answer (i e ‘ one that
`For hand-written or typewriter versions (only) of this report:
`does not require a "Yes“ or “No“ response). please attach an additional page referencing the question number
`FDA will not list patent information ifyou submit an incomplete patent declaration or the patent declaration Indicates the
`patent is not eligible for listing.
`
`For each patent submitted for the pending NDA, amendment. or supplement referenced above, you must submit all the
`information described below. Ifyou are not submitting any patents for this pending NDA. amendment or supplement,
`
`
`lete ab
`ti
`d
`ctlons 5 and 6
`
`a. United States Patent Number
`6,303,861
`
`b Issue Date of Patent
`October 16. 2001
`
`c Expiration Date of Patent
`April 24. 2017
`
`d Name of Patent Owner
`
`Address (of Patent Owner)
`
`PROSiDlON LIMITED
`
`6 Name of agent or representative who
`resides or maintains a place of business
`within the United States authorized to
`receive notice of patent codification under
`section 505(b)(3)and G)(2)(B) of the
`Federal Food. Drug. and Cosmetic Act
`and 21 CFR 314 ,52 and 314 95 (if patent
`owner or NDA applicant/holder does not
`reside or have a place of business within
`the United States)
`
`Watiington Road
`
`City/State
`
`Oxford, United Kingdom
`
`ZIP Code
`OX4 6LT
`
`Telephone Number
`44—1 865182600
`
`FAX Number (if available)
`44-1865-782601
`
`E-Mait Address (if available)
`
`. Address (of agent or representative named in 1 e }
`
`53 South Service Road Suite 110
`'
`
`City/State
`
`Melville. New York
`
`FAX Number (if available)
`631-752-3880
`
`E-Maii Address (if available)
`
`
`
`OSI PHARMACEUTICALS, lNC.
`
`Telephone Number
`631-962—2000
`
`I. is the patent referenced above a patent that has been submitted previously for the
`approved NDA or supplement referenced above?
`it the patent referenced above has been submitted previously for listing. is the
`expiration date a new expiration date?
`FORM FDA 3542a (7103)
`
`9.
`
`N0
`D No
`.
`Page 1
`Computer generated term ‘Patonl Submission with NDA' (Miscellaneous (older) Merck sea . Inc 10i2GI2005
`
`D Yes
`D Yes
`
`

`

`For the patent referenced above, provide the following information on the drug substance, drug product and/or method of use
`that is the subject of the pending NDA, amendment, or supplement.
`
`21 Does the patent claim the drug substance that is the active ingredient in the drug product
`described in the pending NDA. amendment, or supplement?
`
`2.2 Does the patent claim a drug substance that is a different poiymorph of the active
`ingredient described in the NDA, amendment. or supplement?
`2.3 if the answer to question 2.2 is “Yes," do you certify that, as of the date of this declaration.
`you have test data demonstrating that a drug product containing the potymorph will
`perform the same as the drug product described in the NBA? The type of test data
`required is described at 21 CFR 3l4.53(b).
`
`2.4 Specify the polymorphic formis) claimed by the patent for which you have the test results described in 2.3
`
`2.5 Does the patent claim only a metabolite of the active ingredient pending in the NDA or supplement?
`(Complete the information in section 4 below if the patent claims a pending method of using the
`pending drug product to administer the metabolite )
`‘
`
`D Yes
`
`No
`
`2.6 Does the patent claim only an intermediate?
`
`2.? If the patent referenced in 2.1 is a product-by-process patent, is the product claimed in the
`patent novel? (An answer is required only if the patent is a product-by—process patent )
`
`or in patients already being treated with the combination of sitagiiptin and metformin
`
`3.1 Does the patent claim the drug product. as defined in 21 CFR 314 3. in the pending NDA.
`amendment. or su . - lament?
`
`3.2 Does the patent claim only an intermediate?
`
`3.3 if the patent referenced in 3.1 is a product-by—process patent, is the product claimed in the
`patent novel? (An answer is required only if the patent is a product-by-process patent.)
`
`Sponsors must submit the information in section 4 separately for each patent claim claiming a method or using the pending
`drug product for which approval is being sought For each method of use claim referenced, provide the following information:
`4.1 Does the patent claim one or more methods of use for which approval is being sought
`in the I-endin NDA. amendment. or so lament?
`-
`-
`
`4.2 Claim Number (as listed in the patent)
`
`1
`
`‘Does the patent claim referenced in 42 claim a
`pending method of use for which approval is being
`sought in the pending NDA. amendment.
`or supplement?
`
`'
`
`Yes D No
`
`4.23 if the answer to 4,2 is Use: (Submit indication or. method ofuse inionnallon as identified specifically in the proposed labeling.)
`"Yes." identify with
`JANUMET is indicated as an adjunct to diet and exercise to Improve glycemic mntrol in patients
`specificity the use
`with reference to
`with type 2 diabetes mellltus who are not adequately conroied on metfonnin or sltagliptln alone
`the proposed labeling
`for the drug products
`
`
`FORM FDA 3542a (7/03)
`,
`Page 2
`
`Computer generated ionn “Patent Submission with NDA‘ (Miscellaneous folder) Merck & Co . the 10/25/2005
`
`

`

`
`
`Sponsors must submit the informa tion in section‘4 separately for each patent claim claiming a method of using the pending
`drug product for which approval ls being sought. For each method of use claim referenced. provide the following Information:
`
`41 Does the patent claim one or more methods of use for which approval is being sought
`
`
`in the endln- NDA. amendment. or s‘u niement?
`
`
`
`4.2 Claim Number (as listed in the patent)
` Does the patent claim referenced in 42 claim a
`
`pending method of use for which approval is being
`
`sought in the pending NDA. amendment,
`YES D No
`
`or supplement?
`.
`
`
`4.23 if the answer 10 43 is
`Use: (Submit indication or method of use information as identified specifically in the proposed labeling.)
`“Yes!" identity With
`JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in patients
`5995mm" the use
`with type 2 diabetes mellitus who are not adequately controlled on metformig or sitagliptin alone
`W'm reference 1°
`or in patients already being treated with the combination of sltagllptln and metformln
`the proposed labeling
`for the drug product
`
`
`
`
`
`
`
`
`Sponsorsmust submit the information in section 4 separately for each patent claim claiming a methodof using the pending
`drug product for which approval is being sought. For each method of use claim referenced, provide the following information:
`
`Yes D No
`4.1 Does the patent claim one or more methods oigse for which approval is being sought
`
`
`in the uendin NDA. amendment. or su ulement?
`
`Does the patent claim referenced in 4.2 claim a
`
`
`pending method of use for which approval is being
`{2] Yes D No
`sought in the pending NDA. amendment.
`
`
`or supplement?
`
`
`4.2a If the answer to 4.2 is
`Use: (Submit indication or method of use information as identified specifically in the proposed labeling.)
`
`
`"Yes!“ identity with
`JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in patients
`
`specrficrty the use
`with type 2 diabetes mellltus who are not adequately controlled on metformin or sitagliptln alone
`
`
`Wllh reference 10
`or in patients already being treated with the combination of sitagllplin and metformin.
`the proposed labeling
`
`for the drug product
`
`4‘2 Claim Number (as listed in the patent)
`
`
`
`
`Sponsors must submit the information in section 4 separately for each patent claim claiming a method of using the pending
`dru- roduct for which a . -rbvai is both - sou-
`ht. For each method of use claim referenced -rovlde the followin . information:
`
`
`
`
`4.1 Does the patent claim one or more methods of use for which approval is being sought
`
`in the pending NDA. amendment, or supplement?
`
`
`
`Does the patent claim referenced in 42 claim a
`4.2 Claim Number (as listed in the patent)
`
`
`pending method of use 'for which approval is being
`
`
`Yes D No
`sought in the pending NDA. amendment.
`or supplement?
`
`4.23 jf the answer go 42 55
`Use: (Submit indication or method of use information as identified specifically in the proposed labeling.)
`
`"Yes; ldenllfy With
`JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in patients
`$985!“th the use
`with type 2 diabetes mellitus who are not adequately controlled on metformln or sltagllptln alone
`
`Wllh reference 10
`or in patients already being treated with the combination of sitagliptin and mellormin
`
`the proposed labeling
`for the drug product
`
`
`
`
`
`
`Sponsors must submit the information in section 4 separately for each patent claim claiming a method of using the pending
`drug
`
`roduct for which approval is being sought. For each method of use claim referenced, provide the following information:
`4.1 Does the patent claim one or moremeihods of use for which approval is being sought
`
`
`in the pending NDA, amendment, or supplement?
`Does the patent claim referenced in 42 claim a
`
`
`4.2 Claim Number (as listed in the patent)
`pending method of use for which approval is being
`
`sought in the pending NDA. amendment,
`1:, Yes D No
`
`
`or supplement?
`
`
`4.23 If the answer to 42 is
`Use: (Submit indication or method of use information as identified specifically in the proposed labeling.)
`
`
`“Yes," identify with
`
`specificity the use
`with reference to
`
`the proposed labeling
`
`for the drug product
`
`
`
`FORM FDA 3542a (7103)
`
`Page 3
`Compuicrgeneraled lorm 'F‘alenl Submission wilh NDA‘ (Miscellaneous lotder) Merck 8. Co .lnc t0l26l2005
`
`

`

`
`
`%€ XW
`
`NDA A "cant/Holder
`
`NDA Applicant'slHolder's Attorney. Agent (Representative)
`
`NOTE: Only an NBA applicantlholder may submit this declaration directly to the FDA. A patent owner who is not the NDA
`applicant/holder is authorized to sign the declaration but may not submlt it directly to FDA. 21 CFR 314.53(c)(4) and (dud).
`Check applicable box and provide information below.
`
`For this pending NDA. amendment or Supplement, there are no relevant patents that claim the approved drug substance
`(active ingredie