1
`
`Brief Description of Significant Activities Undertaken by Applicant during the
`Regulatory Review Period
`
`Xarelto® Rivaroxaban
`
`Brief Description of Contact/Activity
`
`Submission of initial IND a lication
`FDA acknowledged IND submission; June 30, 2002 effective date
`of IND
`
`Date of FDA
`Contact
`
`May 29, 2002
`June 5, 2002
`
`
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`Submission of harm/tox re ort PH-32303
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`—
`January 15, 2003
`FDA acknowledgement of Bayer Co T-orate Name Change
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`FDA confirmed by hone Ty e C meetin date
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`June 24, 2003
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`‘
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`Submission of Briefing Document
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`November 10, 2003
`
`Submission of 6 pharm/tox reports PH-32735, PH-3 2791, PH-_
`
`December 17, 2003
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`
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`Submission of 7 pharm/tox reports PH-32948, PH-32946, PH-
`
`
`32846, PH-32913, PH-32914, PH-33015, and PH-33056.
`
`M1
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`MYLAN - EXHIBIT 1006 - Part 3 of 14
`
`0515
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`0515
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`MYLAN - EXHIBIT 1006 - Part 3 of 14
`
`

`
`January 9, 2004
`January 19, 2004
`March 1, 2004
`March 10, 2004
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`May 19, 2004
`
`May 26, 2004
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`
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`June 17, 2004
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`Submission of Revised IB, version 7.1
`Submission of Sub-study 10944/ 10945
`Submission of Protocol Amendment study 10945
`Submission of 5 pharm/tox reports PH-31969A, PH-31991A, PH-
`32966, PH-33092, and R-8340.
`
`Informed FDA by phone that highest dose in study 10944 was
`discontinued
`
`Informed FDA by letter that highest dose in study 10944 was
`discontinued
`
`
`Submission of 4 pharm/tox reports PH-33250, PH-33256, PH-
`33273, and PH-33320.
`Submission of 8 new clinical reports: study 10842, study 10842
`Amendment, study 10992, study 10847, study 10991, study 10993,
`
`
`study 11127, and PH-33230.
`
`
`Submission of Annual Re 011
`July 28, 2004
`Submission of Revised IB, version 8
`July 30, 2004
`
`August 16, 2004
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`
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`Submission of response to FDA question/comments received
`
`November 19, 2002 regarding pharm/tox review.
`
`Submission of pharm/tox report PH-33256
`Submission of Protocol Amendment #2 study 10945
`Se tember 7, 2004
`
`Submission of clinical report PH-33444;
`October 26, 2004
`
`
`Submission of 5 pharm/tox reports PH-33368, PH-33380, PH-
`33395, PH-33414, and PH—33434.
`
`
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`
`
`
`December 2, 2004
`Submission of harm/tox re ort PH-33496
`December 10, 2004
`Submission of safety data
`—
`January 20, 2005
`Submission of 4 pharm/tox reports PH-33561, PH-33582, PH-
`‘
`33609, and PH—33611;
`
`
`
`
`
`Submission of 4 clinical reports MRR-00081, MRR-00081A, PH-
`33003, PH-33308
`
`PH-33582, PH—33599, and MRR—00086
`
`Submission of 8 pharrn/tox reports: PH-33320, PH-33582, PH-
`
`33599, PH-33623, PH-33681, PH-33718, PH-33719, PH-33780
`
`Submission Request for Special Protocol Assessment, 2-yr
`carcinogenicity studies
`-
`Submission of 2 pharm/tox reports: PH-33051A, PH-3 3755;
`Submission of 5 clinical reports: PH-33730, PH-32952, PH-33775,
`PH-33776, PH-33 800.
`
`
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`
`
`FDA recommendations received regarding Request for Special
`
`Protocol Assessment, 2-yr carcinogenicity studies
`
`M2
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`0516
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`March 23, 2005
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`April 19, 2005
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`May 4, 2005
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`0516
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`

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`
`Submission of 9 pharm/tox reports: PH-33092A, PH-33230A, PH-
`33880, PH—33897, PH-33902, PH—33906, PH—33916, PH—33917, and
`PH—33918.
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`August 4, 2005
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`November 10, 2005
`
`Submission 3 pharrn/tox reports: PH-34045, PH-34088,and PH-
`34107
`
`
`
`uestions
`
`
`
`
`FDA Official Minute
`f T 6 Meeting received
`
`
`
`FDA Faxed res
`’
`3 C Meeting uestions
`FDA Type,
`
`T
`_A éeting cancelled;
`Submission 2 harm/tox;
`PH—33395 and PH-34138
`Submission 4 clinical reports :7 PH-3395 1 , PH-34102, PH-34035,
`PH-33957
`
`
`
`December 2, 2005
`
`December 8, 2005
`
`
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`
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`December 14, 2005
`
`December 22, 2005
`
`Submission of pharm/tox report: PH-34235;
`Submission of request for Special Protocol Assessment study 11354; _
`Submission of re uest for goecial Protocol Assessment study 11357.
`
`
`Submission request for Special Protocol Assessment 2 year
`
`carcinogenicity studies; Submission of request for Special Protocol
`Assessment study 11356;
`
`
`Submission of reuest for S ecial Protocol Assessment study 11355.
`
`
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`
`
`0517
`
`Submission Operations Manual and DSMB Charter‘ for Phase 3
`studies; Submission of CMC information
`
`
`
`January 19, 2006
`
`January 27, 2006
`January 31, 2006
`
`FDA Comments received re: SPAS for studies 11354 and 11357
`Bayer Agreed to accept FDA requested changes for SPAS for studies
`11354 and 11357
`
`February 3, 2006
`February 6, 2006
`-
`
`FDA Comments received re: SPAS for studies 11355 and 11356
`Submission 3 pharrn/tox reports: PH—34189, PH-34198,and PH-
`34235
`
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`M3
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`0517
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`FDA Faxed Official Minutes of Teleconference Feb. 23.
`
`May 22, 2006
`June 1, 2006
`_ June 2, 2006
`
`June 5, 2006
`
`June 9, 2006
`
`.
`
`Submission of Revised IB, version 11
`FDA teleconference re: carcinogenicity rotocols
`FDA Faxed Official Minutes of teleconference re: carcinogenicity
`rotocols
`Submission of clinical reort MRR 00174
`
`
`
`Re-submitted SPA request for carcinogenicity studies;
`Submission of Revised IB, version 11 amend. 1
`
`November 7, 2006
`
`Submission of 6 pharm/tox reports: PH-31969, PH-33092, PH-
`33230, PH-34897, PH-34610, and PH-34647
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`Discussed “rolling” NDA with FDA
`December 5, 2006
`Submission of CMC Information Amendment
`December 15, 2006
`—
`January 10, 2007
`Submission of a harm/tox reort: PH-34553
`
`
`
`M4
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`
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`0518
`
`0518
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`

`
`Study
`
`August 23, 2007
`August 28, 2007
`
`Brief Discussion of eCTD format for NDA
`Submit Briefing Document for Type C Pre-NDA FDA Meeting;
`Submit Annual Re ort
`
`Se tember 10, 2007
`Se tember 14, 2007
`Se tember 24, 2007
`Setember 27, 2007
`Se tember 28, 2007
`October 2, 2007
`October 3, 2007
`October 11, 2007
`October 12, 2007
`October 17, 2007
`October 19, 2007
`October 22, 2007
`November 8, 2007
`November 9, 2007
`
`Re uest T e B Pre-NDA CMC Meeting
`Re uest Ty e B re—NDA Meeting to Discuss eCTD
`FDA Responses Received for Set. 27 Pre-NDA Meeting
`FDA Pre-NDA Meeting Long Term Safety Data and NDA Date
`Confirmation of FDA Pre-NDA CMC Meeting Date
`FDA Confirmed Date for Pre-NDA eCTD Meeting
`Discussed Postoning 2 FDA Confirmed Meetings
`Cancelled Pre-NDA Meeting Scheduled for Nov. 15
`Submit Briefing Document for T _o B CMC Pre-NDA Meeting
`FDA Tentatively Scheduled Pre-NDA eCTD “demo” Meeting
`Official FDA Minutes of Setember 27 FDA Meeting Received
`FDA Confirmed re-scheduled Pre-NDA eCTD “demo” Meeting
`FDA Resonses Received for Nov. 16 CMC Pre-NDA Meeting
`Submit Briefing Document for Tye B Pre-NDA eCTD Meeting
`
`Pre-NDA eCTD Meeting
`December 13, 2007
`Notify FDA of Bayer’s New Co orate Name and NJ Address
`December 20, 2007
`_
`January 11, 2008
`FDA Official Minutes of Dec. 13 Pre-NDA eCTD Meeting
`
`M5
`
`0519
`
`0519
`
`

`
`
`
`February 14, 2008
`February 15, 2008
`March 5, 2008
`March 17, 2008
`
`March 20, 2008
`
`March 24, 2008
`
`
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`
`
`Subrriit “Stat.” Resonse F/U to Dec. 13 and Jan. 29 Meetings
`Submit Interim Results of Mouse Carcinogenicity Study
`
`FDA Res onse to Interim Mouse Carcinogenicity Results
`
`Submission of CMC Irifoimation Amendment
`
`FDA Response to CMC Proposal; FDA Requested a “Stat.”
`Teleconference
`
`Submission of CMC Information Amendment;
`FDA Acknowledged Receit of Co goorate Name Change
`FDA “Stat.” Teleconference
`
`FDA Official Minutes of March 25 “Stat” Teleconfemece
`Submit Resonse to “Stat.” Teleconference
`
`
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`
`
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`
`
`
`August 7, 2008
`
`NDA Introduction Meeting corres ondence
`
`European Final Summary Product Characteristics (SPC) &
`
`Amendment to the RECORD 4 MRR (AA41 857) Study Reort
`
`Se tember 3, 2008
`
`Inform FDA that IND Transfer to J&J Effective Aug 15
`SAE (Serious Adverse Event) Reorting Unblinding of Subjects
`
`October 15, 2008
`
`October 22, 2008
`
`Call with FDA re CMC and Labeling Comments in Filing Letter
`and Pro osal for Two Meetings
`FDA CMC Re uest for Information
`
`Follow-up Call on CMC, NDA questions, Trade Name and Liver
`
`Subrrussion of Safety Data, including information on CMC, ISS,
`Unblmded SAES
`
`_ N
`
`October 31, 2008
`
`ovember 6, 2008
`
`November 14, 2008
`
`Submission of RECORD 4 Data with Dr. D. Craig Loucks
`
`
`
`
`
`’M6
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`0520
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`0520
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`

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`November 21, 2008
`
`
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`Submission in Response to Office of Compliance Request re:
`RECORD 4 Study ICFs
`
`Pharmacology Sections
`
`Ins o ection
`
`J
`
`December 12, 2008
`December 12, 2008
`
`December 16, 2008
`December 16, 2008
`December 16, 2008
`December 18, 2008
`
`December 19, 2008
`December 24, 2008
`December 30, 2008
`
`Letter from FDA: NDA Clinical Section Review: RFI
`Follow-up on Mid-Cycle Questions, CMC Telecon Minutes, SSP,
`and Clinical Questions
`Statistical Datasets; Res onse to Information Re uest Letter
`December 12, 2008 IR Letter Clarification
`IR Letter Clarification/Dataset Size Clarification
`Information request: CRFs
`
`Res onse to Information Reuest Letter: CMC, Stats, ClinPharm
`Unblinded SAES
`Fax from FDA: Ins ections in Shanghai, China
`
`January 7, 2009
`
`Response to Information Request Letter: Response to Statistics
`Question 2b
`
`January 16, 2009
`
`Follow—up Call with FDA on IR Responses and 6 Month Safety
`Udate Timeline
`
`January 27, 2009
`
`January 27, 2009
`
`January 28, 2009
`
`January 28, 2009
`
`Response to Question 1c of Information Request Letter (December
`12, 2008
`Telecon with Division Director Regarding FDA Advisory
`Committee Meeting March 19, 2009
`Letter from FDA: January 16, 2009 Official Meeting
`(Teleconference Minutes
`Letter from FDA: January 23, 2009 Ofiicial Meeting
`Teleconference Minutes
`
`January 29, 2009
`
` Res onses to Information Re uest Letter (December 12, 2008)
`
`
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`M7
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`0521
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`0521
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`

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`
`
`January 30, 2009 I Response to Question 3 of Information Request Letter (January 12,
`
`2009
`
`January 30, 2009
`February 2, 2009
`
`February 2, 2009
`February 2, 2009
`February 5, 2009
`
`Follow-u on February 2, 2009 Telecon Attendees
`Response to Questions 7, 8, and 9 of Information Request (January
`21, 2009)
`Submission of 6 Month Safety 4- date
`FDA Telecon: February 2, 2009 Meeting Partici ants
`Letter from FDA: Disci line Review Letter
`
`Comments
`
`Document
`
`February 13, 2009
`
`Email from FDA: Information Re uest
`
`— (Teleconference) Minutes
`
`
`
`February 25, 2009
`
`Response to Question 1 of Discipline Review Letter (February 5,
`2009
`
`March 4, 2009
`
`— Question 2 ofDisciline Review Letter (February 5, 2009)
`
`Response to Information Request Letter (February 19, 2009) and
`
`March 6, 2009
`March 11, 2009
`March 11, 2009
`
`March 12, 2009
`
`ebruary 20, 2009
`Resonses to Information Re uest
`Resonses to Information Reuest (March 10, 2009)
`Additional Information in Response to Q2 of Information Request
`Letter February 19, 2009)
`Clarification of Response to Information Request (February 13,
`2009
`
`March 25, 2009
`
`March 26, 2009
`
`March 26, 2009
`
`Clarification of Response to Information Request (February 13,
`2009 and March 4, 2009)
`Follow-up Call re: Request from Biopharmaceutics Reviewer for
`Individual Dissolution Results
`
`i
`
`Email to FDA: Biopharmaceutics Request for Rivaroxaban
`Dissolution Information
`
`March 26, 2009
`
`Res onse to Information Reuest March 6, 2009
`
`
`
`
`
`M8
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`0522
`
`0522
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`

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`Responses to Agency Recommendations and Revised Proposal for
`0 2a of the Comlete Res onse Letter
`Su lemental Audit Plan for Q1 c of the Comlete Res onse Letter
`Letter from FDA: 19 Jun 2009 Official Meeting Minutes
`DA Recommendation for a New Liver Adjudication Panel (NDA
`
`F
`
`
`
`
`M9
`
`0523
`
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`April 9, 2009
`
`Email/Attachments to FDA: Response to April 1, 2009 Information
`Request-Background Information for Record 4 Sites 14010, 14004,
`and 14045
`
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`April 29, 2009
`Aril 30, 2009
`May 1, 2009
`
`May 5, 2009
`May 11, 2009
`May 11, 2009
`May 19, 2009
`
`May 20, 2009
`
`May 20, 2009
`
`May 21, 2009
`May 27, 2009
`
`May 28, 2009
`
`May 29, 2009
`June 5, 2009
`
`June 8, 2009
`
`June 10, 2009
`
`June 11, 2009
`
`June 16, 2009
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`June 18, 2009
`June 18, 2009
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`June 19, 2009
`
`July 2, 2009
`
`July 8, 2009
`July 14, 2009
`July 14, 2009
`
`
`
`
`
`Follow-u Call re: CMC Ins ection Scheduling (Wu ertal)
`Letter from FDA: 21 Ar 2009 Official Meeting Minutes
`Letter from FDA: CMC Section DMF Files 21580, 21581, and
`21592 Inadeuate to Su ort the NDA
`Module 1 Financial Disclosure
`Udate on PDUFA Date
`CMC Amendment for Trade Blister Packs
`Additional Clarification to Response to Information Request 1 (20
`Feb 2009)
`_o dated Investigator’ s Brochure
`DMF Res onses: DMF 21592, DMF 21580, DMF 21581
`CMC Amendment for Trade Blister Packs
`
`Letter from FDA complete response to NDA (Review with
`Comments and Recommendations
`
`FDA Complete Response Letter (27 May 2009) Proposed
`Clarifications Meeting
`Reuest for Tye A Telecon/Meeting
`Follow-up Call re: Quality Items in Comlete Res onse Letter
`Comlete Res onse Letter — Clarification Questions
`Pro osal for Addressing Comlete Res onse Letter
`Additional Clarification on Q2a Comlete Res go onse Pro osal
`Comlete Res onse Letter Clarification
`Comlete Res onse Letter corres ondence
`
`Follow-up Call re: Clarification Responses from FDA to Telecon 19
`Jun 3:00 to 4:30 PM EST
`
`FDA Meeting Minutes Complete Response Clarifications
`Teleconference
`
`NDA Complete Response Letter — Question 2(a) and IND 75,931
`
`ACS SAP
`
`0523
`
`

`
`
`
`
` 22-406 Comlete Res onse Clarification Meeting Minutes)
`Email from FDA: Draft Comments on Proposed Supplemental Audit
`Plan
`
`FDA teleconference minutes-clarification on FDA CR Letter
`
`Letter from FDA: Feedback on Suplemental Audit Plan
`Email with Attachment from FDA: Feedback from the ONDQA
`Project Manager on Questions about the CRL fiom CMC RA
`Email from FDA: Res onse to FDA CRL Labeling
`7- dated Patent Information
`Letter with Attaclnnent from FDA: Memorandum of Teleconference
`Minutes of 31 Jul 2009
`
`FDA Comments on the Proposed Liver Adjudication Panel
`Procedural Charter (NDA 22-406 Complete Response Clarification
`Meeting Minutes)
`
`Patent 3 date
`Email from FDA: eCTD File Question and Resonse
`FDA Teleconference minutes on un-blinding of liver data LAP
`Letter from FDA: 13 Nov 2009 Official Meeting Minutes
`
`Tye A Meeting Re uest
`Letter from FDA: Meeting Granted 05 Mar 2010
`FDA Type C Meeting — 05 Mar 2010 — To be Rescheduled
`T e C Meeting Background Information 07 Ar 2010
`Email to FDA: Meeting Background Package; FYI — 7 Ar Meeting
`Email from FDA: Meeting Background Package; To Opt Out of
`Meeting
`
`FDA Response to Rivaroxaban Cross Referencing Proposal in the
`NDA e-mail
`
`FDA Meeting re: Falcon and Bayer Audits
`J&J Submission of Falcon/Bayer Audits to FDA (DSI) (Follow—up
`to 7 Ar 2010 Meeting)
`FDA Letter re: Warning Letter Issued by FDA to Craig Buettner
`regarding Conduct of a Study
`Com lete Resonse Tirnefrarne Extension Re uest
`
`
`
`
`FDA Letter re: ‘Notice of Initiation of Disqualification Proceedings
`
`and go ortunity to Ex lain” letter issued to Dr. David Craig Loucks
`Ofiicial Meeting Minutes of 07 Aril 2010
`FDA Letter Granting Extension until 27 May 2011 the
`Resubmission of a Complete Response to FDA Action Letter dated
`27 May 2009
`
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`July 29, 2009
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`July 31, 2009
`August 14, 2009
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`August 28, 2009
`
`Au ust 28, 2009
`October 6, 2009
`October 13, 2009
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`October 13, 2009
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`October 21, 2009
`
`November 2, 2009
`
`—
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`
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`March 8, 2010
`
`April 7, 2010
`
`A - ril 7, 20 1 0
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`April 19, 2010
`
`April 27, 2010
`
`Aril 29, 2010
`April 30, 2010
`
`May 7, 2010
`
`May 10, 2010
`
`June 10, 2010
`
`August 2, 2010
`
`
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`
`
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`
`
`Complete Response — Record 4 Study Data Verification SAP (Study
`1 135 5)
`Information Request — Written Response due on or before 30
`August 2010
`
`August 6, 2010
`
`
`
`Email to FDA regarding DSI Feedback on the Falcon and Bayer
`
`
`
`M10
`
`0524
`
`0524
`
`

`
` audits — Clarification Re uested
`Email to FDA regarding Clarification for FDA DSI Requests for
`Additional Datasets
`
`_ A
`
`ugust 10,2010
`
`Email from FDA regarding Clarification for FDA DSI Requests for
`Additional Datasets; Res onses Noted
`Telecon Minutes —CR DSI Information Re uest of 02- Aug-2010
`Type C Meeting Request to obtain guidance and concurrence from
`the Agency regarding the rivaroxaban exposures in special
`
`
`opoulations of interest and otential dose reduction
`CR DSI IR Response Bayer and Falcon Audits for the RECORD
`Studies and Reference to the DSI Information Request Received 02
`Aug 2010
`CR Renal DDI Study Meeting Request (telecom) — FDA Meeting
`Granted Letter Attached — Type C Meeting Teleconference
`
`Scheduled for 14-Oct-10
`J&J Resonse to DSI IR Q2 and Q3 of August 2, 2010 (cover letter)
`Summary of FDA teleconference on Renal DDI Study Meeting from
`14-Oct-10
`
`
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`Question on Resubmission of documents — Infonnation may be
`linked no need to submit twice
`
`T e C Meeting Minutes from 14-Oct-2010 Meeting
`FDA Draft Label in Word Format Agreement
`Foreign Labeling Question — Pro To osal is Accetable
`FDA Additional Analyses Re uest
`S onsor Comlete Res onse filed 30-Dec-2010
`
`
`
`
`
`Notification of Amendment to DMF 21592 which includes updated
`site specific stability data and stability evaluation, as well as updated
`container closure descri tion information
`
`August 11,2010
`
`August 23, 2010
`September 2, 2010
`
`September 7, 2010
`
`September 13, 2010
`
`Se tember 24, 2010
`October 14, 2010
`
`October 15, 2010
`
`October 15, 2010
`
`October 20, 2010
`
`January 4, 2011
`
`
`
`
`
`
`
`January 13, 2011
`
`Acknowledgement for Receipt of Complete Response CMC in pdf
`form
`
`January 13, 2011
`
`Screen Shot of Module 1 to Assist in location of Complete Response
`Document
`
`
`
`Liver—related safety information from studies ROCKET AF 11630,
`J-ROCKET 12620, EINSTEIN 11702, EINSTEIN Extension 11899,
`EINSTEIN PE 11702
`
`Call re: email request from ONDQA project manager for location of
`Bayer stability commitment as request in 27-May-2009 agency
`com lete res onse letter
`
`
`
`
`
`
`
`
`FDA in receipt of 30-Dec-2010 resubrnission - complete Class 2
`Resonse to 27-May-2009 action letter
`Information request fiom the FDA Hematology division for clinical
`narratives in a SAS dataset
`
`General Corresondence Res onse to IR 27-Jan-2011
`Teleconference Scheduled to Discuss the Patient Narratives
`
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`Provided in the Comlete Resonse is cancelled
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`Clinical Pharmacology Section in Submission — Information
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`Clarification of a Typographical Error — for Rivaroxaban, not
`Section 505(b) for Hearin Sodium Injection
`Res onse to Information Re uest IR dated 07-Feb-2011
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`Request for Proprietary Name Review: Primary Name: XARELTO
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`rivaroxaban) Alternate Name: Not Submitted
`Copy of Cover Letter and Request for Proprietary Name Review
`Provided to the Division of Medication Error Prevention and
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`March 25, 2011
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`Aril18, 2011
`Ari12l, 2011
`Aril25, 2011
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`Request from ONDQA Project Manager for Updated 356h
`Establishment Information for NDA 22-406; Follow-up re: Timing
`for Dissolution Res o onse
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`Establishment U date
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`Agency Information Re uest Relating to DMF 21580 CMC Section
`Resonse to IR 14-Ar-2011
`Udated Resonse to IR 14-Ar-2011
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`Res onse to CMC Information Re uest of 08-Ar-201 1
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`Request for Bayer Pooled Adverse Events Analysis Dataset for
`EINSTEIN DVT — 11702, Extension — 11899, and EINSTEIN PE —
`11702 with Cutoff Date of 31-Dec-2010
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`CMC Dissolution Specification for Rivaroxaban 15mg and 20mg
`Tablets
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`Drug Product Specification Update and DMF 21529 Update
`Notification
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`Response to Information Request of 27-Apr-2011 — Bayer Pooled
`Adverse Events Analysis Dataset for EINSTEIN DVT (11702)
`Extension 11899) and EINSTEIN PE 11702)
`Updated 10mg Packaging Comonents
`Coy of DMF 21592 Information Into Module 3 of NDA
`Courtesy Copy of DIVIF 21592 Information Into Module 3 of NDA
`Submission — Cover Letter and CMC Information
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`Agency Notification That the Proposed Proprietary Name,
`XARELTO, is Conditionally Acce table
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`Information Re uest Regarding the Label
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`Information Request Regarding Tables for SAES, AEs, Bleeding
`Events, and Drug-Related AEs Based on an Integrated Safety
`Analysis for RECORD 1-3, Excludin RECORD 4
`Response to Information Request of 17-May-2011 and 19-May-
`201 1
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`Res onse to Information Re uest of 02-Jun-2011
`FDA Sending Draft USPI Within a Few Da s
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`Comments Regarding FDA Label Review Request and Change of
`S To onsor Name
`Label Review with Comments
`Res onse to Information Reuest - Hy ersensitivity Cases
`Final Version of the GPC Consulting Report and the RECORD 1-4
`Justification Reuest
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`June 16, 2011
`June 17, 2011
`June 17, 2011
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`PMR — PMC Comments
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`Company Name Change and Updated Label Components Based on
`FDA Comments
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`FDA Minutes of Teleconference to Discuss Bleeding in Table 1 of
`the Label
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`Agreement to Teleconferences with FDA-Telecon with Clinical
`Pharmacology on 23-Jun-2011 and Telecon with Representatives of
`the Division of Scientific Investigations DRI and Clinical on 27-Jun-
`201 1
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`Clarification on the Post Marketing Re uirement
`Final Pro - osed Post-marketing Re a uest
`Agency Comments to Sponsor Response to FDA Regarding Draft
`Label
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`Meeting Minutes from the 23-Jun-2011 Teleconference Regarding
`the Clinical Pharmacolo ; Section of the Label
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`Background Material for the 27-Jun-2011 Meeting Regarding the
`RECORD 4 Study
`PMR Clarification Re uest Extension for Submission of Tirneline
`Sponsor Res onse to FDA Label Comments
`Agency Acknowledgement of Corporate Name Change from Ortho-
`McNeil-Janssen Pharmaceuticals, Inc. to Janssen Pharmaceuticals,
`Inc. for XARELTO
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`Two Issues from Review of Updates to the Carton and Label
`Containers
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`Updated PMC for Review With Request to Confirm Agreement and
`to Let Agency Know If Tirnelines Remain the Same
`Updated Label with Updates and Comments Under Table 2 Footnote
`and in Section 12.3
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`Udated Labels for the Bottle, Carton, and HUD Blister
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`Notification that USPI for 30-Jun-2011 Meeting Will Be Sent
`Final PI Provided
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`PMRs (Post-Marketing Reviews) and PMC (Post-Marketing
`Commitment Provided for Review
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`A 0 roval Letter for NDA 22-406
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`June 17, 201 l
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`Patent Number: 7,157,456
`
`Attorney Docket Number: 1 1987-00014—US
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`H\I RE U.S. PATENT NO. 7,157,456 B2
`
`ISSUED: January 2, 2007
`
`INVENTORS: Alexander Straub et al.
`
`FOR: Substituted Oxazolidinones and Their Use in the Field of Blood Coagulation
`
`Office of Patent Legal Administration
`
`600Dl
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`s
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`Room MDW 7D55
`Alexai11dzi'Ii1€Z\7tlI:E2t2(31:
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`-
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`Md’
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`B'1d'
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`lson ul mg)
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`-"0
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`RECENED“
`N36
` ED
`' qnfl
`OPLAb\\f‘ " 5
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`PA
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`Sir:
`
`Enclosed is an application for the extension of U.S. Patent No. 7,157,456 under
`
`35 U.S.C. §156.
`
`Accompanying this Transmittal is authorization to charge the Application Fee of
`
`$1,120.00 prescribed by 37 C.F.R. §1.20(j)(1), as well as any additional fees which may
`
`be necessitated in connection with the filing of this Application for Patent Term
`
`Extension, to the undersigned’s credit card. If any additional fees are due, the
`
`Commissioner is hereby authorized to charge to Deposit Account No. 03-2775.
`
`Dated: August 25, 2011
`
`Respectfully Submitted
`
`Christine M. Hansen
`
`Registration No. 40,634
`Connolly Bove Lodge & Hutz LLP
`1007 North Orange Street
`P .0. Box 2207
`
`Wilmington, DE 19899
`Attorney for Applicant
`
`Enclosures:
`
`Patent Tenn Extension Application including Appendices
`
`683632—l
`
`0529
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`0529
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`

`
`PTO/SB/81A (1208)
`Approved foruse lhrough 11/30/2011, OMB 0651-0035
`US. Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
`Underihe Paperwork Reduction Act M1995. no persons am required to nsspond to a coiiaction ofinformalion uniess ii displays a valid OMB control number.
`
`
`
`First Named Inventor
`
`Patent Number
`Janua
`2, 2007
`Alexander Siraub
`
`
`
`Tme
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`
`
`
`
`PATENT — POWER OF ATTORNEY
`
`OR
`REVOCATION OF POWER OF ATTORNEY
`WITH A NEW POWER OF ATTORNEY
`AND
`
`
`
`
`
`SUBSTITUTED OXAZOLIDINONES AND
`THEIR USE IN THE FIELD OF BLOOD...
`'1 1987-0O0‘i4~US
`CHANGE OF CORRESPONDENCE ADDRESS Auomey Dockemo’
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`i hereby revoke ali previous powers of attorney given in the aboveidentified patent.
`
`D A Power of Attorney is submitted herewith.
`
`OR
`
`
`
`
`
`
`
`
`
`I hereby appoint Praciitioner(s) associated with ihe following Customer Number as my/our
`attomeyis) or ageni(s) with respect to the patent identified above, and to transact all business in
`the United Siaies Patent and Trademark Office connected therewith:
`OR
`
`23416
`
`I hereby appoint Praciitioner(s) named beiow as my/our aiiorrrey(s) or agent(s) with respect to the patent ideniified
`above. and lo iransacl ail business in the United Siaias Patent and Trademark Office connected therewith:
`
`Pra<:tiiioner(s) Name
`
`R°§’§n"§;’f"
`
`F'ractiiioner(s) Name
`
`Pi-ease recognize or change the correspondence address for the abovwidentlfied patent to:
`
`
`
`R‘;§fifn"§§’"
`
`
`
`D The address associated with the abovementioned Customer Number.
`OR
`
`
`
`The address associated with Custorner Number:
`OR
`
`23416
`
`
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`Finn or
`individual Name
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`
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`fl——
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`—_I am that
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`0530
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`i’il'9a”d°°mpaW
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`NOTE: Signatures olall the invaniors or patent owner ofthe entire
`man one signature is requirtad. sea beiow‘.
`
`forms are submitted.
`[:1 ‘Total of
`#4,393.808
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`
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`D Inventor. having ownership of ihe paieni.
`OR
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`Patent owner.
`Statement under 37 CFR 3. '/'3(b) (Form PTO/S8/96) subrnifled herewith or flied on
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`Electronic Acknowledgement Receipt
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`10625481
`
`Application Number:
`
`10181051
`
`International Application Number:
`
`Confirmation Number:
`
`Title of Invention:
`
`SUBSTITUTED OXAZOLIDINONES AND THEIR USE IN THE FIELD OF BLOOD
`COAGULAHON
`
`First Named Inventor/Applicant Name:
`
`Alexander Straub
`
`Customer Number:
`
`23416
`
`Christine Hansen/Amy Hamm
`
`Filer Authorized By:
`
`Christine Hansen
`
`Attorney Docket Number:
`
`LE A 34122
`
`Receipt Date:
`
`29-JU L—201 1
`
`Filing Date:
`
`24-JUN—2002
`
`Time Stamp:
`
`10:19:11
`
`Application Type:
`
`U.S. National Stage under 35 USC 371
`
`Payment information:
`
`Submitted with Payment
`
`File Listing:
`
`Document
`Number
`
`Document Description
`
`(if appl.)
`
`File Size(Bytes)/
`Message Digest
`147357
`
`Multi
`
`Part /.zip
`
`Pages
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`456_POA.pdf
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`a9f1fee1b2912fe1402f1a3bb9ad1404b4cf
`e73
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`0531
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`Multipart Description/PDF files in .zip description
`
`Assigneeshowing ofownershipper37CFR3.73(b).
`
`Information:
`
`This Acknowledgement Receipt evidences receipt on the noted date by the USPTO ofthe indicated documents,
`characterized by the applicant, and including page counts, where applicable. It serves as evidence of receipt similar to a
`Post Card, as described in MPEP 503.
`
`New Applications Under 35 U.S.C. 111
`lfa new application is being filed and the application includes the necessary components for a filing date (see 37 CFR
`1.53(b)-(d) and MPEP 506), a Filing Receipt (37 CFR 1.54) will be issued in due course and the date shown on this
`Acknowledgement Receipt will establish the filing date of the application.
`
`National Stage of an International Application under 35 U.S.C. 371
`lfa timely submission to enter the national stage of an international application is compliant with the conditions of 35
`U.S.C. 371 and other applicable requirements a Form PCT/DO/E0/903 indicating acceptance of the application as a
`national stage submission under 35 U.S.C. 371 will be issued in addition to the Filing Receipt, in due course.
`
`New International Application Filed with the USPTO as a Receiving Office
`lfa new international application is being filed and the international application includes the necessary components for
`an international filing date (see PCT Article 11 and MPEP 1810), a Notification of the International Application Number
`and ofthe International Filing Date (Form PCT/R0/105) will be issued in due course, subject to prescriptions concerning
`national security, and the date shown on this Acknowledgement Receipt will establish the international filing date of
`the application.
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`
`PTO/SB/96 (07-09)
`Approved for use through 07/31/2012. OMB 0651-0031
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paenrvork Reduction Act of 1995, no ersons are reuired to resond to a collection of information unless it disla s a valid OMB control number.
`
`STATEMENT UNDER 37 CFR 3.73§b[
`
`Applicant/Patent Owner:
`
`Alexander Straub et al.
`
`Application No./Patent No.:
`January 2, 2007
`Filed/Issue Date:
`7,157,456
`Titled:
`SUBSTITUTED OXAZOLIDINONES AND THEIR USE IN THE FIELD OF BLOOD
`COAGULATION
`
`Bayer Pharma Aktiengesellschaft
`(Name of Assignee)
`states that it is:
`
`, a
`
`Corporation
`(Type of Assignee, e.g., corporation, partnership, university, government agency, etc.)
`
`1.
`
`the assignee of the entire right, title, and interest in;
`
`2. D an assignee of less than the entire right, title, and interest in
`(The extent (by percentage) of its ownership interest is
`
`%); or
`
`3. D an assignee of an undivided interest in the entirety of (a complete assignment from one of thejoint inventors was made)
`the patent application/patent identified above by virtue of either:
`
`A. I: An assignment from the inventor(s) of the patent application/patent identified above. The assignment was
`recorded in the United States Patent and Trademark Office at Reel
`,
`Frame
`, or for which a copy thereof is attached.
`
`OR
`
`B_
`
`A chain of title from the inventor(s), of the patent application/patent identified above, to the current assignee as follows:
`1. From:
`Alexander Straub et al.
`To:
`Bayer Aktiengesellschaft
`The document was recorded in the United States Patent and Trademark Office at
`
`Reel
`
`013411
`
`, Frame
`
`0223
`
`, or for which a copy thereof is attached.
`
`Bayer Healthcare Aktiengesellschaft
`To:
`Bayer Aktiengesellschaft
`2. From:
`The document was recorded in the United States Patent and Trademark Office at
`
`Reel
`
`015004
`
`, Frame
`
`0466
`
`, or for which a copy thereof is attached.
`
`Bayer Schering Pharma
`Aktlengesellschaft
`To:
`Bayer Healthcare AG
`3. From:
`The document was recorded in the United States Patent and Trademark Office at
`
`Reel
`
`023769
`
`, Frame
`
`0122
`
`, or for which a copy thereof is attached.
`
`Additional documents in the chain of title are listed on a supplemental sheet( ).
`
`As required by 37 CFR 3.73(b)(1)(i), the documentary evidence of the chain of title from the original owner to the
`assignee was, or concurrently is being, submitted for recordation pursuant to 37 CFR 3.11.
`
`[NOTE: A separate copy (i.e., a true copy of the original assignment document(s)) must be submitted to Assignment
`Division in accordance with 37 CFR Part 3, to record the assignment in the records of the USPTO. gag MPEP 302.08]
`
`The undersigned (whose title is supplied below) is authorized to act on behalf of the assignee.
`
`/Christine M. Hansen/
`Signature
`
`Christine M. Hansen
`Printed or Typed Name
`
`July 29, 2011
`Date
`
`AttorneLfor Assignee
`Title
`
`4410899
`
`0533
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`SUPPLEMENTAL SHEET FOR USE WITH PTO/SB/96 (07-09)
`
`Bayer Schering Pharma AG
`To:
`Bayer Healthcare AG
`4. From:
`The document was recorded in the United States Patent and Trademark Office at
`
`, or for which a copy thereof is attached.
`, Frame
`022520
`Reel
`To:
`Bayer Schering Pharma AG
`Bayer Healthcare AG
`5. From:
`The document was recorded