8306€40
`
`1!Q)A'l1Jl,'!lQ>Wli~Ir'llH!E·S~ ~ES\E~1!1~Sif.l!\tffi,~MIEl~
`UNITEDSTATESDEPARTMENTOFCOMMERCE
`United States Patent and Trademark Office
`
`October 20, 2022
`
`THIS IS TO CERTIFY THAT ANNEXED IS A TRUE COPY FROM THE
`RECORDS OF TIDS OFFICE OF THE FILE WRAPPER AND CONTENTS
`OF:
`
`APPLICATION NUMBER: 16/055,847
`FILING DATE: August 6, 2018
`PATENT NUMBER: 10,857,205
`ISSUE DATE: December 8, 2020
`
`By Authority of the
`Under Secretary of Commerce for Intellectual Property
`and Director of the United States Patent and Trademark Office
`
`Certifying Officer
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 001
`
`

`

`DocCode - SEQ.TXT
`
`SCORE Placeholder Sheet for IFW Content
`
`Application Number: 1605584 7
`
`Document Date: 08/06/2018
`
`The presence of this form in the IFW record indicates that the following document type was received
`in electronic format on the date identified above. This content is stored in the SCORE database.
`
`Since this was an electronic submission, there is no physical artifact folder, no artifact folder is
`recorded in PALM, and no paper documents or physical media exist. The TIFF images in the IFW
`record were created from the original documents that are stored in SCORE.
`
`• Sequence Listing
`
`At the time of document entry (noted above):
`• USPTO employees may access SCORE content via eDAN using the Supplemental Content
`tab, or via the SCORE web page.
`• External customers may access SCORE content via PAIR using the Supplemental Content
`tab.
`
`Form Revision Date: August 26, 2013
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 002
`
`

`

`PRELIMINARY
`AMENDMENT
`Under CFR 1.115
`
`Address to:
`Mail Stop Patent Application
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`Electronically Filed
`Attorney Docket No.
`REGN-008CIPCON3
`To Be Assigned
`Confirmation No.
`Y ANCOPOULOS, GEORGE D.
`First Named Inventor
`To Be Assigned
`Application Number
`Filing Date
`August 6, 2018
`To Be Assigned
`Group Art Unit
`To Be Assigned
`Examiner Name
`Title:
`"Use of a VEGF Antagonist to Treat Angiogenic
`Eve Disorders"
`
`Prior to the examination of the above-referenced application on the merits, please enter the
`amendments below.
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 003
`
`

`

`AMENDMENTS TO THE SPECIFICATION
`
`Atty Dkt. No.: REGN-008CIPCON3
`USSN: To Be Assigned
`
`Please amend paragraph [0001] on pagel of the specification to read as follows:
`
`[0001] This application is a continuation of U.S. Patent Application Serial No. 15/471,506, filed
`
`March 28, 2017 (now allowed) which is a continuation of U.S. Patent Application Serial No.
`
`14/972,560, filed December 17, 2015, now U.S. Patent No. 9,669,069 issued June 6, 2017 which is a
`
`continuation of U.S. Patent Application Serial No. 13/940,370 filed July 12, 2013, now U.S. Patent
`
`No. 9,254,338 issued February 9, 2016 which is a continuation-in-part of International Patent
`
`Application No. PCT/US2012/020855, filed on January 11, 2012, which claims the benefit of US
`
`Provisional Application Nos. 61/432,245, filed on January 13, 2011, 61/434,836, filed on January 21,
`
`2011, and 61/561,957, filed on November 21, 2011, the contents of which are hereby incorporated by
`
`reference in their entireties.
`
`2
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 004
`
`

`

`Atty Dkt. No.: REGN-008CIPCON3
`USSN: To Be Assigned
`
`AMENDMENTS TO THE CLAIMS
`
`1. - 20. (Canceled)
`
`21.
`
`(New) A method for treating macular edema following retinal vein occlusion in a human
`
`subject comprising administering 2 mg aflibercept to the subject by intravitreal injection once every 4
`
`weeks.
`
`22.
`
`(New) The method of claim 21 wherein the aflibercept is administered in a volume of
`
`0.05 ml.
`
`23.
`
`(New) The method of claim 22 wherein the aflibercept is in a pharmaceutical
`
`formulation comprising a pharmaceutically acceptable carrier.
`
`3
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 005
`
`

`

`Atty Dkt. No.: REGN-008CIPCON3
`USSN: To Be Assigned
`
`REMARKS UNDER 37 CFR § 1.115
`
`Formal Matters
`
`Claims 21-23 are pending after entry of the amendments set forth herein.
`
`Claims 1-20 are canceled without prejudice.
`
`Claims 21-23 are added.
`
`Support for new claim 21 can be found at paragraph [0010] and throughout the specification.
`
`Support for new claim 22 can be found at paragraph [0070] and throughout the specification.
`
`Support for new claim 23 can be found at paragraph [0027] and throughout the specification.
`
`The specification has been amended to update the cross-reference to related application section.
`
`No new matter has been added.
`
`PARENT APPLICATION
`
`The parent application has been allowed. Further, as indicated above, correspondence and
`
`support for the current claims relative to those of the parent application can be reviewed and confirmed.
`
`In the event the Examiner has any questions with respect to claim support or other issues in connection
`
`with the application, the Examiner is respectfully requested to contact the undersigned attorney at the
`
`indicated telephone number to arrange for an interview to expedite this position of this application.
`
`STATEMENT UNDER 37 C.F.R. §§1.56 AND 1.2
`
`Applicants hereby advise the Examiner of the status of a co-pending application in compliance
`
`with the Applicant's duty to disclose under 37 C.F.R. §§1.56 and 1.2 ( see also MPEP §2001.06(b)) as
`
`discussed in McKesson Info. Soln. Inc., v. Bridge Medical Inc., 487 F.3d 897; 82 USPQ2d 1865 (Fed.
`
`Cir. 2007).
`
`The Applicants wish to bring to the Examiner's attention U.S. Patent Application No.
`
`13/940,370, filed July 12, 2013 which issued on February 9, 2016 as U.S. Patent 9,254,338.
`
`The Applicants wish to bring to the Examiner's attention U.S. Patent Application No.
`
`14/972,560, filed December 17, 2015 which issued on June 6, 2018 as U.S. Patent No. 9,669,069.
`
`The Applicants wish to bring to the Examiner's attention that a Notice of Allowance was mailed
`
`on July 26, 2018 in co-pending U.S. Patent Application No. 15/471,506, filed March 28, 2018.
`
`4
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 006
`
`

`

`Atty Dkt. No.: REGN-008CIPCON3
`USSN: To Be Assigned
`
`These documents are available on PAIR, and thus are not provided with this
`
`communication. Please inform the undersigned if there is any difficulty in obtaining the documents
`
`from PAIR.
`
`CONCLUSION
`
`Applicant submits that all of the claims are in condition for allowance, which action is requested.
`
`If the Examiner finds that a telephone conference would expedite the prosecution of this application,
`
`please telephone the undersigned at the number provided.
`
`The Commissioner is hereby authorized to charge any underpayment of fees up to a strict limit of
`
`$3,000.00 beyond that authorized on the credit card, but not more than $3,000.00 in additional fees due
`
`with any communication for the above referenced patent application, including but not limited to any
`
`necessary fees for extensions of time, or credit any overpayment of any amount to Deposit Account No.
`
`50-0815, order number REGN-008CIPCON3.
`
`Respectfully submitted,
`BOZICEVIC, FIELD & FRANCIS LLP
`
`By: -~/=K=ar=l~B~o~z=ic~e~v~ic~,~R~e"-"g=·~N~o~·~2~8~,8~0~7~/_
`Karl Bozicevic
`Registration No. 28,807
`
`Date: ---~6~A~u_,_gu=s~t~2~0~1~8 _ _ _
`
`Bozicevic, Field & Francis LLP
`201 Redwood Shores Parkway, Suite 200
`Redwood City, California 94065
`Telephone: (650) 327-3400
`Direct: (650) 833-7735
`Facsimile: (650) 327-3231
`
`5
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 007
`
`

`

`Electronically Filed 8/6/2018
`Attorney Docket No.
`Confirmation No.
`First Named Inventor
`Application Number
`Filing Date
`Group Art Unit
`Examiner Name
`
`REGN-008CIPCON3
`To Be Assigned
`GEORGE D. YANCOPOULOS
`To Be Assi_gned
`Au_gust 6, 2018
`
`Title: "Use of a VEGF Antagonist to Treat Angiogenic
`Eye Disorders"
`
`INFORMATION
`DISCLOSURE STATEMENT
`
`Address to:
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`Applicants submit herewith documents which may be material to the examination of this application
`
`and in respect of which there may be a duty to disclose in accordance with 37 C.F.R. § 1.56. This submission
`
`is not intended to constitute an admission that any document referred to therein is "prior art" for this invention
`
`unless specifically designated as such. A listing of the documents is shown on enclosed Form PTO/SB/08A.
`
`The Examiner is requested to make the documents listed on the enclosed PTO/SB/08A of record in this
`
`application. Applicants would appreciate the Examiner initialing and returning the initialed copy of form
`
`PTO/SB/08A, indicating the documents cited therein have been considered and made of record herein.
`
`All of the references identified herein were disclosed in parent application serial number 15/471,506,
`
`and as such, copies thereof are not included pursuant to the provisions of 37 CFR § 1.98(d).
`
`Statements
`
`~ No statement
`
`D
`
`PTA Statement under 37 CFR § 1.704(d)(l): Each item of information contained in
`
`the information disclosure statement filed herewith:
`
`(i) Was first cited in any communication from a patent office in a counterpart foreign or
`
`international application or from the Office, and this communication was not received
`
`by any individual designated in § 1.56( c) more than thirty days prior to the filing of the
`
`information disclosure statement; or
`
`(ii) Is a communication that was issued by a patent office in a counterpart foreign or
`
`international application or by the Office, and this communication was not received by
`
`any individual designated in § 1.56(c) more than thirty days prior to the filing of the
`
`information disclosure statement.
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 008
`
`

`

`Atty Docket No.: REGN-008CIPCON3
`USSN: To Be Assigned
`
`D
`
`D
`
`IDS Statement under 37 CFR § 1.97(e)(l): Each item of information contained in the
`
`information disclosure statement was first cited in any communication from a foreign
`
`patent office in a counterpart foreign application not more than three months prior to the
`
`filing of the information disclosure statement; or
`
`IDS Statement under 37 CFR § 1.97(e)(2): No item of information contained in the
`
`information disclosure statement was cited in a communication from a foreign patent
`
`office in a counterpart foreign application, and, to the knowledge of the person signing
`
`the certification after making reasonable inquiry, no item of information contained in
`
`the information disclosure statement was known to any individual designated in §
`
`1.56( c) more than three months prior to the filing of the information disclosure
`
`statement.
`
`Fees
`
`~ No fee is believed to be due.
`D
`
`The appropriate fee set forth in 37 C.F.R. §1.17(p) accompanies this information disclosure
`
`statement.
`
`The Commissioner is hereby authorized to charge any underpayment of fees up to a strict limit of
`
`$3,000.00 beyond that authorized on the credit card, but not more than $3,000.00 in additional fees due with
`
`any communication for the above referenced patent application, including but not limited to any necessary fees
`
`for extensions of time, or credit any overpayment of any amount to Deposit Account No. 50-0815, order
`
`number REGN-008CIPCON3.
`
`Date: August 6, 2018
`
`BOZICEVIC, FIELD & FRANCIS LLP
`201 Redwood Shores Parkway, Suite 200
`Redwood City, CA 94065
`Telephone: (650) 327-3400
`Facsimile: (650) 327-3231
`
`Respectfully submitted,
`BOZICEVIC, FIELD & FRANCIS LLP
`
`By: -~/=K=ar=l~B~o=z=i~ce~v=i=c,~R=e-g_...~N~o~-~2~8~,8~0~7~/ __
`Karl Bozicevic
`Reg. No. 28,807
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 009
`
`

`

`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`
`Sheet I
`
`1
`
`I of I
`
`3
`
`Application Number
`Filing Date
`First Named Inventor
`Art Unit
`Examiner Name
`Attorney Docket Number
`
`To Be Assii:ined
`August6,2018
`YANCOPOULOS, GEORGE D.
`N/A
`N/A
`REGN-008CIPCON3
`
`Examiner
`Initial*
`
`Cite
`No.
`
`1
`
`Patent Number
`
`Number-Kind Code (ii known)
`7396664
`
`U.S. PATENT DOCUMENTS
`Issue Date
`Name of Patentee or
`YYYY-MM-DD
`Applicant of Cited Document
`
`2008-07-08
`
`Daly et al.
`
`U.S. PATENT APPLICATION PUBLICATIONS
`Publication Date
`Name of Patentee or
`YYYY-MM-DD
`Applicant of Cited Document
`
`Publication Number
`
`Number-Kind Code (ii known)
`20050163798
`20050260203
`20060058234
`20060172944
`20070190058
`20030171320
`
`2005-07-28
`2005-11-24
`2006-03-16
`2006-08-03
`2007-08-16
`2003-09-11
`
`Papadopoulos et al.
`Wiegand et al.
`Daly et al.
`Wiegand et al.
`Shams
`Guyer
`
`FOREIGN PATENT DOCUMENTS
`Publication Date
`Name of Patentee or
`YYYY-MM-DD
`Applicant of Cited Document
`
`Examiner
`Initial*
`
`Cite
`No.
`
`1
`2
`3
`4
`5
`6
`
`Examiner
`Initial*
`
`Cite
`No.
`1
`
`Pages, Columns, Lines, Where
`Relevant Passages or Relevant
`FiQures Appear
`
`Pages, Columns, Lines, Where
`Relevant Passages or Relevant
`Fiaures Aooear
`
`Pages, Columns, Lines,
`Where Relevant Passages
`or Relevant Figures
`Aooear
`
`T
`
`Foreian Document Number
`
`Country Code-Number-Kind Code (ii
`known)
`
`WO 2000/75319
`
`2000-12-14
`
`Regeneron
`Pharmaceuitcals, Inc.
`
`Regeneron
`Pharmaceuticals, Inc.
`
`2 WO 2007/022101 A2
`
`2007-02-22
`
`3 WO 2008/063932
`
`2008-05-29
`
`Genentech, Inc.
`
`4
`
`JP 2010-509369
`
`2010-03-25
`
`Genentech, Inc.
`
`See WO 2008/063932
`for English Equivalent
`
`NON PATENT LITERATURE DOCUMENTS
`
`Examin
`er
`Initials*
`
`1
`
`Cite
`Include name of the author (in CAPITAL LETTERS), title of the article (when appropriate), title of the item (book,
`No. magazine, journal, serial, symposium, catalog, etc.), date, page(s), volume-issue number(s), publisher, city and/or
`country where published.
`ANONYMOUS "Lucentis (rangibizymab injection) lntravitreal Injection" pp. 103 (June
`2006)
`Information from ClinicalTrials.gov archive View of NCT00637377 "Vascular Endothelial
`2 Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related
`Macular Degeneration (AMO) (VIEW 2)" Clinica/Trials.gov. Web. 2010-11-30.
`
`T
`
`CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 21-756
`MEDICAL REVIEW(S) (December 17, 2004)
`<URL:https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-
`756 Macuaen medr.odf>
`CENTER FOR DRUG EVALUATION AND RESEARCH BLA APPLICATION NUMBER:
`125156 MEDICAL REVIEW, (June 2006)
`<URL:https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s000_Lucentis_
`MedR.pdf>
`CHARLES, Steve (Guest Lecturer) "VEGF Trap Has Positive DME Data" Tenth Annual
`Retina Fellows Forum Jan 29 and 30, Chicaao, Article Date 03/01/2010
`
`3
`
`4
`
`5
`
`I Date
`I Examiner
`~
`Si nature
`Considered
`EXAl◊~~ER. llliliiii lleielel,Ce 6611§,deled, Wlleuiel bi 1161 Ciliiubll I§ Iii 6611,blliiiillCe Wiui l◊IPEP 609 DiiiW ,Ille 1111600116111(1611 II 1161 Iii 6611,blliiiillCe 11116 1161
`considered. Include copy of this form with next communication to applicant.
`
`I
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 010
`
`

`

`T
`
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`
`Sheet I
`
`2
`
`I of I
`
`3
`
`Application Number
`Filing Date
`First Named Inventor
`Art Unit
`Examiner Name
`Attorney Docket Number
`
`To Be Assii:ined
`August6,2018
`YANCOPOULOS, GEORGE D.
`N/A
`N/A
`REGN-008CIPCON3
`
`NON PATENT LITERATURE DOCUMENTS
`
`Examin
`er
`Initials*
`
`6
`
`7
`
`8
`
`9
`
`Cite
`Include name of the author (in CAPITAL LETTERS), title of the article (when appropriate), title of the item (book,
`No. magazine, journal, serial, symposium, catalog, etc.), date, page(s), volume-issue number(s), publisher, city and/or
`country where published.
`DIXON et al., "VEGF Trap-Eye for the treatment of neobascular age-related macular
`deqeneration" Expert Opin. lnvestiq. Druqs (2009) 18 (10): 1-8.
`DO et al., "An exploratory study of the safety, tolerability and bioactivity of a single
`intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic
`macular oedema" Br J Opthamol. 93(2) :144-1449 (February 2009)
`DO et al., "The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients
`with diabetic macular edema" Opthamoloqy 118(9) :1819-1826 (September 2011)
`THE EYETECH STUDY GROUP, "Anti-Vascular Endothelial Growth Factor Therapy for
`Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration"
`American Academy of Ophthamology, 110(5):979-986 (May 2003)
`HEIERet al.," rhuFab V2 (anti-VEGF Antibody) for Treatment of Exudative AMO"
`10 Symposium 8:Experimental and Emerging Treatments for Choroidal Neovascularization,
`10 DD (2002)
`HEIER et al., "RhuFab V2 in Wet AMO - 6 Month Continued Improvement Following
`11
`Multiple lntravitreal Injections" Invest Ophthalmol Vis Sci, 44:E-Abstract 972 (2003)
`12 HEIER et al., "lntravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related macular
`Deqeneration," Ophthalmoloqy, 119:2537-2548 (2012)
`Information from ClinicalTrials.gov archive on the VIEW 2 study (NCT00637377) "VEGF
`Trap-Eye: Investigation of Efficacy and Safety in Wet AMO (VIEW 2)" version available
`and updated on 17 March 2008.
`Information from ClinicalTrials.gov archive on the view of NCT00509795 "Vascular
`Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet
`Aqe-Related Macular Deqeneration (AMO)" (12-01-2009)
`Information from ClinicalTrials.gov archive on the view of NCT00789477 "DME and VEGF
`Trap-Eye: lnvestiqation of Clinical Impact" (11-18-2010)
`Information from ClinicalTrials.gov archive on the view of NCT00509795 "Vascular
`Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet
`Aqe-Related Macular Deqeneration (AMO)" (01-07-2011)
`KRZYSTOLIK et al., "Prevention of Experimental Choroidal NEovascularization With
`lntravitreal Anti-Vascular Endothelial Growth Factor Antibody Fragment" Arch
`Ophthamol., 120:338-346 (Mar. 2002)
`MITRA et al., "Review of anti-vascular endothelial growth factor therapy in macular edema
`secondary to central retinal vein occlusions" Expert Review in Ophthalmo, Taylor &
`Francis, GB (January 1, 2011) 6(6):623-629
`19 MOUSA AND MOUSA, "Current Status of Vascular Endothelial Growth Factor Inhibition in
`Aqe-Related Macular Deqeneration" Biodruqs 201 O; 24(3); 183-194.
`NGUYEN et al., "A Phase I Study of lntravitreal Vascular Endothelial Growth Factor Trap-
`Eye in Patients with Neovascular Age-Related Macular Degeneration" Opthamology, J.B.
`Lippincott Co., Philadelphia, PA, US, 116(11 ):2141-2148 (November 1, 2009)
`116(11) :2141-2148 (November 1, 2009)
`NGUYEN et al., "A phase I trial of an IV-administered vascular endothelial growth factor
`trap for treatment in patients with choroidal neovascularization due to age-related macular
`deqeneration" Ophthalmoloqy (Sept 2006) 113(9) :1522e1-1522e14 (epub July 28,2006)
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`20
`
`21
`
`I Date
`I Examiner
`~
`Si nature
`Considered
`EXAl◊~~ER. llliliiii lleielel,Ce 6611§,deled, Wlleuiel bi 1161 Ciliiubll I§ Iii 6611,blliiiillCe Wiui l◊IPEP 609 DiiiW ,Ille 1111600116111(1611 II 1161 Iii 6611,blliiiillCe 11116 1161
`considered. Include copy of this form with next communication to applicant.
`
`I
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 011
`
`

`

`T
`
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`
`Sheet I
`
`3
`
`I of I
`
`3
`
`Application Number
`Filing Date
`First Named Inventor
`Art Unit
`Examiner Name
`Attorney Docket Number
`
`To Be Assii:ined
`August6,2018
`YANCOPOULOS, GEORGE D.
`N/A
`N/A
`REGN-008CIPCON3
`
`NON PATENT LITERATURE DOCUMENTS
`
`Examin
`er
`Initials*
`
`24
`
`Cite
`Include name of the author (in CAPITAL LETTERS), title of the article (when appropriate), title of the item (book,
`No. magazine, journal, serial, symposium, catalog, etc.), date, page(s), volume-issue number(s), publisher, city and/or
`country where published.
`NICHOLS, EARL R., "AAO: Ranibizumab (rhuRab) May Improve Vision in Age-Related
`22 Macular Degeneration" Doctor's Guide Global Edition, www.pslgroup.com/dg/23f2aa.htm,
`DD. 1-2 (November 24, 20013)
`23 OLIVERA et al., "VEGF Trap R1 R2 suppresses experimental corneal angiogenesis"
`European Journal of Ophthalmology (January 1, 2010) 20(1 ):48-54
`PAI et al., "Current concepts in intravitreal drug therapy for diabetic retinopathy" Saudi
`Journal of Opthamology
`24(4):143-149 (June 30, 2010)
`25 Regeneron Pharmaceuticals, Inc. FORM 1 0-Q, published on 7 November 2007 for the
`period ending 30 September 2007
`26 Regeneron, Press release "Regeneron Reports First Quarter 2008 Financial and
`Operatinq Results", May 1, 2008.
`Regeneron Press Release "Bayer and Regeneron Report Positive Top-Line Results of
`Two Phase 3 Studies with VEGF Trap-Eye in Wet Age-related Macular Degeneration"
`November 22, 2010
`Regeneron Press Release "Regeneron and Bayer Report Positive Results for VEGF
`Trap-Eye in Phase 3 Study in Central Retinal Vein Occlusion (CRVO) and in Phase 2
`Study in Diabetic Macular Edema (DME)" December 20, 2010
`Regeneron Pharmaceuticals Inc., "VEGF Trap-Eye Final Phase 2 Results in Age-related
`29 Macular Degeneration Presented at 2008 Retina Society Meeting" (September 28, 2008)
`(XP-002770952)
`30 SIMO AND HERNANDEZ, "Advances in Medical Treatment of Diabetic Retinopathy"
`Diabetes Care, Volume 32, Number 8, Auqust 2009
`Slides for the 2008 Retina Society Meeting "VEGF Trap-Eye in Wet AMO CLEAR-IT 2:
`31
`Summary of One-Year Key Results", September 28, 2008.
`32 STEWART, "THe expanding role of vascular endothelial growth factor inhibitors in
`opthamoloqy" Mayo Clin Proc. 87(1) :77-88 (January 2012)
`THOMAS REUTERS INTEGRITY "VEGF Trap-Eye final phase II results in age-related
`33
`macular deqeneration presented at 2008 Retina Society Meetinq" (September 28, 2008)
`34 WHO Drug Information, "International Nonproprietary Names for Pharmaceutical
`Substances (INN)" Vol. 20, No. 2, 2006, paqes 115-119.
`
`27
`
`28
`
`I Date
`I Examiner
`~
`Si nature
`Considered
`EXAl◊~~ER. llliliiii lleielel,Ce 6611§,deled, Wlleuiel bi 1161 Ciliiubll I§ Iii 6611,blliiiillCe Wiui l◊IPEP 609 DiiiW ,Ille 1111600116111(1611 II 1161 Iii 6611,blliiiillCe 11116 1161
`considered. Include copy of this form with next communication to applicant.
`
`I
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 012
`
`

`

`Electronically Filed
`
`NOTIFICATION OF PRIOR
`SEQUENCE LISTING
`
`Attorney Docket
`
`REGN-008CIPCON3
`
`First Named Inventor
`
`Y ANCOPOULOS,
`GEORGED.
`
`Address to:
`Mail Stop Patent Application
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`Application Number
`
`To Be Assigned
`
`Filing Date
`
`6 August 2018
`
`Confirmation Number
`
`To Be Assigned
`
`Group Art Unit
`
`To Be Assigned
`
`Examiner Name
`
`To Be Assigned
`
`Title:
`
`"USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS"
`
`The above-identified patent application contains sequences of nucleic acid and
`
`polypeptides. A sequence listing was prepared for parent application, 15/471,506, filed March
`
`28, 2018, in paper and computer-readable format. The sequence information in the paper or
`
`compact disk copy of the sequence listing (required by 1.82l(c)) of this application is identical to
`
`the sequence information in the computer-readable format (CRF) of the above-identified other
`
`application. No new matter has been added. Therefore, please transfer to this application, in
`
`accordance with 37 CFR § 1.82l(e), the fully compliant computer readable copy from applicants'
`
`other application. A paper (.txt) copy of this sequence listing is enclosed.
`
`Applicants respectfully submit that the present patent application is now in compliance
`
`with 37 CFR §§ 1.821 - 1.825. The Commissioner is hereby authorized to charge any
`
`underpayment of fees associated with this communication, including any necessary fees for
`
`extensions of time, or credit any overpayment to Deposit Account No. 50-0815, order number
`
`REGN-008CIPCON3.
`
`Respectfully submitted,
`
`BOZICEVIC, FIELD & FRANCIS LLP
`
`By:
`
`/Karl Bozicevic, Reg. No. 28,807/
`Karl Bozicevic
`Registration No. 28,807
`
`Dated:
`
`6 August 2018
`
`BOZICEVIC, FIELD & FRANCIS LLP
`201 Redwood Shores Parkway, Suite 201
`Redwood City, California 94065
`Telephone: (650) 327-3400
`Facsimile: (650) 327-3231
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 013
`
`

`

`REGN-008CIPCON2_SeqList.txt
`
`SEQUENCE LISTING
`
`<110> George D. Yancopoulos
`
`<120> use of a VEGF Antagonist to Treat Angiogenic Eye Disorders
`
`<130> 725Al
`
`<140> To be assigned
`<141> Filed herewith
`
`<150> PCT/US2012/020855
`<151> 2012-01-11
`
`<150> 61/432,245
`<151> 2011-01-13
`
`<150> 61/434,836
`<151> 2011-01-21
`
`<150> 61/561,957
`<151> 2011-11-21
`
`<160> 2
`
`<170> FastSEQ for windows version 4.0
`
`<210> 1
`<211> 1377
`<212> DNA
`<213> Artificial sequence
`
`<220>
`<223> synthetic
`
`<400> 1
`atggtcagct actgggacac cggggtcctg ctgtgcgcgc tgctcagctg
`acaggatcta gttccggaag tgataccggt agacctttcg tagagatgta
`cccgaaatta tacacatgac tgaaggaagg gagctcgtca ttccctgccg
`cctaacatca ctgttacttt aaaaaagttt ccacttgaca ctttgatccc
`cgcataatct gggacagtag aaagggcttc atcatatcaa atgcaacgta
`gggcttctga cctgtgaagc aacagtcaat gggcatttgt ataagacaaa
`catcgacaaa ccaatacaat catagatgtg gttctgagtc cgtctcatgg
`tctgttggag aaaagcttgt cttaaattgt acagcaagaa ctgaactaaa
`gacttcaact gggaataccc ttcttcgaag catcagcata agaaacttgt
`ctaaaaaccc agtctgggag tgagatgaag aaatttttga gcaccttaac
`gtaacccgga gtgaccaagg attgtacacc tgtgcagcat ccagtgggct
`aagaacagca catttgtcag ggtccatgaa aaggacaaaa ctcacacatg
`ccagcacctg aactcctggg gggaccgtca gtcttcctct tccccccaaa
`accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt
`gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa
`aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct
`caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa
`gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc
`accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac
`aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca
`aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct
`ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc
`gaggctctgc acaaccacta cacgcagaag agcctctccc tgtctccggg
`
`tctgcttctc 60
`cagtgaaatc 120
`ggttacgtca 180
`tgatggaaaa 240
`caaagaaata 300
`ctatctcaca 360
`aattgaacta 420
`tgtggggatt 480
`aaaccgagac 540
`tatagatggt 600
`gatgaccaag 660
`cccaccgtgc 720
`acccaaggac 780
`gagccacgaa 840
`tgccaagaca 900
`caccgtcctg 960
`agccctccca 1020
`acaggtgtac 1080
`ctgcctggtc 1140
`gccggagaac 1200
`ctacagcaag 1260
`cgtgatgcat 1320
`taaatga
`1377
`
`<210> 2
`<211> 458
`
`Page 1
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 014
`
`

`

`REGN-008CIPCON2_SeqList.txt
`
`<212> PRT
`<213> Artificial sequence
`
`<220>
`<223> synthetic
`
`<400> 2
`Met val Ser Tyr Trp Asp Thr Gly val Leu Leu cys Ala Leu Leu Ser
`1
`15
`5
`10
`cys Leu Leu Leu Thr Gly Ser Ser Ser Gly Ser Asp Thr Gly Arg Pro
`20
`25
`30
`Phe val Gl u Met Tyr Ser Gl u Ile Pro Gl u Ile Ile His Met Thr Gl u
`40
`45
`35
`Gly Arg Gl u Leu val Ile Pro cys Arg val Thr Ser Pro Asn Ile Thr
`50
`55
`60
`val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys
`70
`75
`65
`80
`Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr
`85
`90
`95
`Tyr Lys Gl u Ile Gly Leu Leu Thr cys Gl u Ala Thr val Asn Gly His
`110
`100
`105
`Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gl n Thr Asn Thr Ile Ile
`115
`120
`125
`Asp val val Leu Ser Pro Ser His Gly Ile Gl u Leu Ser val Gly Gl u
`140
`130
`135
`Lys Leu val Leu Asn cys Thr Ala Arg Thr Gl u Leu Asn val Gly Ile
`145
`150
`155
`160
`Asp Phe Asn Trp Gl u Tyr Pro Ser Ser Lys His Gl n His Lys Lys Leu
`165
`170
`175
`val Asn Arg Asp Leu Lys Thr Gl n Ser Gly Ser Gl u Met Lys Lys Phe
`180
`185
`190
`Leu Ser Thr Leu Thr Ile Asp Gly val Thr Arg Ser Asp Gl n Gly Leu
`195
`200
`205
`Tyr Thr cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr
`210
`215
`220
`Phe val Arg val His Gl u Lys Asp Lys Thr His Thr cys Pro Pro cys
`225
`230
`235
`240
`Pro Ala Pro Gl u Leu Leu Gly Gly Pro Ser val Phe Leu Phe Pro Pro
`245
`250
`255
`Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Gl u val Thr cys
`260
`265
`270
`val val val Asp val Ser His Gl u Asp Pro Gl u val Lys Phe Asn Trp
`275
`280
`285
`Tyr val Asp Gly val Gl u val His Asn Ala Lys Thr Lys Pro Arg Gl u
`290
`295
`300
`Gl u Gl n Tyr Asn Ser Thr Tyr Arg val val Ser val Leu Thr val Leu
`315
`320
`305
`310
`His Gl n Asp Trp Leu Asn Gly Lys Glu Tyr Lys cys Lys val Ser Asn
`325
`330
`335
`Lys Ala Leu Pro Ala Pro Ile Gl u Lys Thr Ile Ser Lys Ala Lys Gly
`340
`345
`350
`Gl n Pro Arg Gl u Pro Gl n val Tyr Thr Leu Pro Pro Ser Arg Asp Gl u
`355
`360
`365
`Leu Thr Lys Asn Gl n val Ser Leu Thr cys Leu val Lys Gly Phe Tyr
`370
`375
`380
`Pro Ser Asp Ile Al a val Gl u Trp Glu Ser Asn Gly Gl n Pro Gl u Asn
`400
`385
`390
`395
`Asn Tyr Lys Thr Thr Pro Pro val Leu Asp Ser Asp Gly Ser Phe Phe
`405
`410
`415
`Leu Tyr Ser Lys Leu Thr val Asp Lys Ser Arg Trp Gl n Gl n Gly Asn
`420
`425
`430
`val Phe Ser cys Ser val Met His Glu Ala Leu His Asn His Tyr Thr
`435
`440
`445
`
`Page 2
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 015
`
`

`

`REGN-008CIPCON2_SeqList.txt
`Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
`450
`455
`
`Page 3
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 016
`
`

`

`Electronic Patent Application Fee Transmittal
`
`Application Number:
`
`Filing Date:
`
`Title of Invention:
`
`USE OF A VEGF ANTAGONIST TO TREAT ANGIOGENIC EYE DISORDERS
`
`First Named Inventor/Applicant Name:
`
`George D. YANCOPOULOS
`
`Filer:
`
`Attorney Docket Number:
`
`Filed as Large Entity
`
`Filing Fees for Utility under 35 USC 111 (a)
`
`Karl Bozicevic
`
`REGN-008CIPCON3
`
`Description
`
`Fee Code
`
`Quantity
`
`Amount
`
`Sub-Total in
`USO($)
`
`Basic Filing:
`
`UTILITY APPLICATION FILING
`
`UTILITY SEARCH FEE
`
`UTILITY EXAMINATION FEE
`
`1011
`
`1111
`
`1311
`
`1
`
`1
`
`1
`
`300
`
`660
`
`760
`
`300
`
`660
`
`760
`
`Pages:
`
`Claims:
`
`Miscellaneous-Filing:
`
`Petition:
`
`Patent-Appeals-and-Interference:
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 017
`
`

`

`Description
`
`Fee Code
`
`Quantity
`
`Amount
`
`Sub-Total in
`USO($)
`
`Post-Allowance-and-Post-Issuance:
`
`Extension-of-Time:
`
`Miscellaneous:
`
`Total in USO($)
`
`1720
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 018
`
`

`

`Electronic Acknowledgement Receipt
`
`EFSID:
`
`Application Number:
`
`33381499
`
`16055847
`
`International Application Number:
`
`Confirmation Number:
`
`3451
`
`Title of Invention:
`
`USE OF A VEGF ANTAGONIST TO TREAT ANGIOGENIC EYE DISORDERS
`
`First Named Inventor/Applicant Name:
`
`George D. YANCOPOULOS
`
`Customer Number:
`
`96387
`
`Filer:
`
`Karl Bozicevic
`
`Filer Authorized By:
`
`Attorney Docket Number:
`
`REGN-008CIPCON3
`
`Receipt Date:
`
`06-AUG-2018
`
`Filing Date:
`
`Time Stamp:
`
`16:25:48
`
`Application Type:
`
`Utility under 35 USC 111 (a)
`
`Payment information:
`
`Submitted with Payment
`
`Payment Type
`
`Payment was successfully received in RAM
`
`yes
`
`CARD
`
`$1720
`
`RAM confirmation Number
`
`080718INTEFSW16264200
`
`Deposit Account
`
`Authorized User
`
`The Director of the USPTO is hereby authorized to charge indicated fees and credit any overpayment as follows:
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 019
`
`

`

`File Listing:
`
`Document
`Number
`
`1
`
`Warnings:
`
`Information:
`
`Document Description
`
`File Name
`
`File Size(Bytes}/
`Message Digest
`
`Multi
`Part /.zip
`
`Pages
`(if appl.)
`
`153933
`
`REGN-008CIPCON3_2018-08-0t
`_Appln_as_fld.pdf
`
`6121 ec056faa53a9a0bc991 05653645a200
`21d96
`
`yes
`
`24
`
`Multipart Description/PDF files in .zip description
`
`Document Description
`
`Start
`
`End
`
`Specification
`
`Claims
`
`Abstract
`
`21
`
`23
`
`24
`
`1
`
`22
`
`24
`
`105393
`
`2
`
`Drawings-only black and white line
`drawings
`
`REGN-008CIPCON3_Figure.pdf
`
`no
`
`1
`
`2d582f64Sd0c5d 17d717e589b029a39331 ~
`91bdb
`
`Warnings:
`
`The page size in the PDF is too large. The pages should be 8.5 x 11 or A4. If this PDF is submitted, the pages will be resized upon entry into the
`Image File Wrapper and may affect subsequent processing
`
`Information:
`
`3
`
`Oath or Declaration filed
`
`REGN-008CIPCON3_declaration
`.pdf
`
`173097
`
`6bda7272374e6af80c8c3d8cf30d012e465
`b588
`
`no
`
`2
`
`Warnings:
`
`The page size in the PDF is too large. The pages should be 8.5 x 11 or A4. If this PDF is submitted, the pages will be resized upon entry into the
`Image File Wrapper and may affect subsequent processing
`
`Information:
`
`4
`
`Application Data Sheet
`
`WebADS.pdf
`
`no
`
`8
`
`9e5 0 bc4 53 2e6ef83 2de b 1 5 6f7f785 cl f63 2b
`b97
`
`134486
`
`Warnings:
`
`Information:
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 020
`
`

`

`5
`
`49231
`
`REGN-008CIPCON3_2018-08-0t
`_pre_amend_asfld.pdf
`
`607e9ab43