IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re U.S. Patent Number: 7,070,959
`
`(Application No. 10/009,852)
`
`For: Modified Chimeric Polypeptides with
`Improved Pharmacokinetic Properties
`
`Inventors: Papadopoulos, Davis and Yancopoulos
`
`Issued: July 4, 2006
`
`RECEIVED
`DEC 2; 2 2011
`PATENT EXTENSION
`OPLA
`
`Assignee: Regeneron Pharmaceuticals, Inc.
`
`Unit: OPLA
`
`Office of Patent Legal Administration (via hand delivery)
`Room MDW 7D55
`600 Dulany Street (Madison Building)
`Alexandria, VA 22314
`
`APPLICATION FOR EXTENSION OF PATENT TERM UNDER 35 U.S.C. §156
`
`Dear Sir,
`
`Applicant, Regeneron Pharmaceuticals, Inc., hereby submits this application
`for extension of the term of United States Letters Patent No. 7,070,959 (the '"'959
`patent") under 35 U.S.C. §156 and 37 C.F.R §1.740.
`
`Applicant represents that it is the assignee of the entire interest in and to the
`'959 patent by virtue of assignment of all rights of inventors Nicholas J. Papadopoulos,
`Samuel Davis and George D. Yancopoulos (Papadopoulos et al.) to Regeneron
`Pharmaceuticals, Inc., as recorded in the U.S. Patent and Trademark Office on August
`13, 2001, Reel 012077, Frame 0978 and on February 19, 2002, Reel 012639, Frame
`0222 (a copy of each is attached in Attachment A).
`00000010 180&50
`0510912012 CKHLOK
`01 FC:1457
`1120,00 DA
`
`7070959
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 1
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 2
`
`This application is based on the approval by the United States Food and Drug
`Administration ("FDA") of a Biologics License Application (BLA No. BL 125387 /0) on
`November 18, 2011, for EYLEA ™ (aflibercept intravitreal injection, also known as
`aflibercept IVT, aflibercept ophthalmic injection and aflibercept ophthalmic solution).
`
`1.
`
`Identification of the Approved Product under 37 C.F.R. §1.740 (a)(1)
`
`The name of the approved product is EYLEA™. The name of the active
`ingredient of EYLEA™ is aflibercept, also known as VEGF trap, VEGF-trap, VEGF Trap(cid:173)
`Eye and VEGF-TRAPR1R2- Aflibercept is a fusion protein consisting of (a) a vascular
`endothelial growth factor (VEGF) receptor component having immunoglobulin-like
`(lg) domains consisting of an lg domain 2 of a first VEGF receptor that is human Fltl
`and an lg domain 3 of a second VEGF receptor that is human Flkl; and (b) an Fe
`portion of human lgGl.
`
`2.
`
`Federal Statute Governing Regulatory Approval of the Approved Product
`under 37 C.F.R. §1.740(a)(2)
`
`The approved product was subject to regulatory review under, inter alia, the
`Public Health Service Act ( 42 U.S.C. § 201 et seq., including 42 U.S.C. §262(a)) and the
`Federal Food, Drug and Cosmetic Act (21 U.S.C. § 355 et seq.).
`
`3.
`
`Date of Approval for Commercial Marketing under 37 C.F.R. §1.740 (a)(3)
`
`EYLEA™ was approved for commercial marketing or use under §351 of the
`Public Health Service Act on November 18, 2011.
`
`4.
`
`(a)
`
`(b)
`
`Identification of Active Ingredient and Certifications Related to
`Commercial Marketing of Approved Product under 37 C.F.R. §1.740(a)(4)
`
`The active ingredient of EYLEA™ is aflibercept, which is a recombinant
`fusion protein consisting of a VEGF receptor component having lg domains
`consisting of an lg domain 2 of human Fltl and an lg domain 3 of human
`Flkl, fused to the Fe domain of human lgGl.
`
`Applicant certifies that aflibercept has not been approved for commercial
`marketing or use under the Federal Food, Drug and Cosmetic Act, the
`Public Health Service Act or the Virus-Serum-Toxin Act prior to the
`approval granted on November 18, 2011 to the present Applicant.
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 2
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 3
`
`(c)
`
`(d)
`
`Aflibercept has been approved for the treatment of patients with
`neovascular (wet) age-related macular degeneration. See EYLEN,., product
`label, provided as Attachment B.
`
`EYLEA™, whose active ingredient is aflibercept, was approved for
`commercial marketing pursuant to§ 351 of the Public Health Service Act
`( 42 U.S.C. §262) under Regeneron's existing Department of Health and
`Human Services (DHHS) U.S. License No. 1760. See EYLEA™ approval
`letter, provided as Attachment C.
`
`5.
`
`Statement Regarding Timeliness of Submission of Patent Term Extension
`Request[§ 1.740(a)(5)]
`
`Applicant certifies that this application for patent term extension is being
`submitted within the sixty (60) day period permitted for submission specified
`in 35 U.S.C. § 156(d)(l), (as amended on September 16, 2011), and 37 C.F.R. §
`1.720(t). The amended provisions of the America Invents Act state that the
`date on which a product receives permission is the next business day if
`permission is "transmitted after 4:30 P.M., Eastern Time, on a business day
`.... " Permission was transmitted to Applicant at 5:47 P.M., Eastern Time, on
`Friday, November 18, 2011, a business day. The next business day is Monday,
`November 21, 2011. Accordingly, the last date on which this application may
`be submitted is January 19, 2012.
`
`6.
`
`Complete Identification of the Patent for Which Extension Is Being Sought
`[§ 1.740(a)(6)]
`
`The complete identification of the patent for which an extension is being
`sought is as follows:
`
`(a) Names of the inventors:
`
`Nicholas J. Papadopoulos, Samuel Davis and
`George D. Yancopoulos
`
`(b) Patent Number:
`
`U.S. Patent No. 7,070,959 ("the '959
`patent")
`
`(c) Date of Issue:
`
`July 4, 2006
`
`( d) Date of Expiration :
`
`May 23, 2020
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 3
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 4
`
`7.
`
`Copy of the Patent for Which an Extension is Being Sought[§ 1.740(a)(7)]
`
`A copy of the '959 patent is provided as Attachment D to the present
`application.
`
`8.
`
`Copies of Disclaimers, Certificates of Correction, Receipt of Maintenance
`Fee Payment, or Reexamination Certificate[§ 1.740(a)(8)]
`
`The '959 patent is subject to a terminal disclaimer, a copy of which is
`(a)
`attached in Attachment E.
`
`(b)
`
`No certificate of correction has been issued for the '959 patent.
`
`(c)
`
`( d)
`
`The first maintenance fee for the '959 patent was timely paid on
`January 4, 2010 (a copy of the Maintenance Fee Statement is attached
`here as Attachment F).
`
`The '959 patent has not been the subject of a reexamination
`proceeding.
`
`9.
`
`Statement Regarding Patent Claims Relative to Approved Product
`[§ 1.740(a)(9)]
`
`The statements below are made solely to comply with the requirements of 3 7
`C.F R. § 1.740 (a)(9). Applicant notes that, as the M.P.E.P. acknowledges,§ 1.740 (a){9)
`does not require an applicant to show whether or how the listed claims would be
`infringed, and that this question cannot be answered without specific knowledge
`concerning acts performed by third parties. As such, these comments are not an
`assertion or an admission of Applicant as to the scope of the listed claims, or whether or
`how any of the listed claims would be infringed, literally or under the doctrine of
`equivalents, by the manufacture, use, sale, offer for sale or the importation of any
`product.
`
`At least the following claim of the '959 patent claims a method of
`(a)
`manufacturing the approved product: claim 11.
`
`(b)
`
`Pursuant to M.P.E.P. § 2753 and 37 C.F.R. § 1.740(a)(9), the following
`explanation is provided which shows how the above-listed claim of the
`'959 patent claims a method of manufacturing the approved product.
`
`(1)
`
`Description of the approved product
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 4
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 5
`
`The approved product is described as follows in the approved
`label for EYLEA™, a copy of which is provided as Attachment B.
`
`EYLEA™ (aflibercept ophthalmic solution) is a recombinant
`fusion protein consisting of portions of human VEGF receptors 1 and 2
`extracellular domains fused to the Fe portion of human lgGl and
`specially purified and formulated as an iso-osmotic solution for
`intravitreal administration. Aflibercept is a dimeric glycoprotein with a
`protein molecular weight of 97 kilodaltons (kDa) and is glycosylated,
`with the glycosylation constituting an additional 15% of the total
`molecular mass, resulting in a total molecular weight of 115 kDa.
`
`Aflibercept is also described in Holash et al. Proc. Natl. Acad. Sci.
`USA, August 20, 2002, Vol. 99, No. 17, pp. 11393-11398 ("Holash,"
`Attachment G) as VEGF-TrapR1R2, which has the lg domain 2 ofVEGF
`receptor 1 (VEGFR1; also known as Flt-1) fused to the lg domain 3 of
`VEGF receptor 2 (VEGFR2; also known as Flk-1), which in turn is fused
`to the constant region (Fe) of human lgGl. See paragraph bridging
`pages 11393 and 11394 and Figure 1A.
`
`As noted in Section 11 of the EYLEA™ label (Attachment B),
`aflibercept is produced in Chinese hamster ovary (CHO) Kl cells by
`recombinant DNA technology. Holash (Attachment G) also describes the
`method of producing aflibercept (VEGF-TrapRrn2) as expressing a
`recombinant DNA construct in Chinese hamster ovary cells (See
`"Engineering VEGF-Traps" in the Materials and Methods section on
`page 11393-11394).
`
`(2)
`
`Explanation Regarding Claim 11 Relative to Aflibercept
`
`As explained below, a method for manufacturing aflibercept, the
`active ingredient of the approved product, is covered by at least claim
`11.
`
`Claim 11 reads as follows:
`
`A method of producing a fusion polypeptide, comprising
`11.
`growing cells of the host-vector system of claim 8, under
`conditions permitting production of the fusion polypeptide and
`recovering the fusion polypeptide so produced.
`
`Claim 11 depends from claim 8, which reads as follows:
`
`8.
`
`A host-vector system for the production of a fusion
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 5
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 6
`
`polypeptide comprising an expression vector encoding a fusion
`protein capable of binding VEGF, wherein the fusion protein
`consists of immunoglobulin-like (lg) domain 2 ofVEGF receptor
`human Fltl, lg domain 3 ofVEGF receptor human Flkl, and a
`multimerizing component, in a suitable isolated host cell.
`
`Comparison ofaflibercept to Claim 11
`
`As noted above, aflibercept is a recombinant fusion protein
`having an lg domain 2 from VEGFRl fused to an lg domain 3 from
`VEGFR2 (See Holash (Attachment G), paragraph bridging pages 11393
`and 11394 and Figure lA). The '959 patent refers to VEGFR-1 as Fltl in
`column 25, line 43, and refers to VEGFR-2 as Flkl in column 25, line 65.
`In addition, Holash discloses that VEGFR-1 is also known as Flt-1 and
`that VEGFR-2 is also known as Flk-1. See Figure lA of Holash.
`Aflibercept also comprises the Fe domain of human lgGl fused to the
`extracellular domains from the VEGF receptors. See Section 11 of
`EYLEA™ label, provided as Attachment B. As described in the '959
`patent, a "multimerizing component" of the fusion protein includes an
`immunoglobulin domain, such as the Fe domain of IgG. See col. 5, lines
`38-42 and col. 7, lines 14-19. Aflibercept binds VEGF, as described in
`Section 12.1 of the EYLEA™ label (Attachment B). Thus, aflibercept is a
`fusion protein that is capable of binding VEGF and that consists of lg
`domain 2 ofVEGF receptor human Flt-1, lg domain 3 of VEGF receptor
`human Flk-1, and a multimerizing component as encoded by the
`expression vector defined in claim 8.
`
`Claim 11 describes a method of producing the fusion polypeptide
`encoded by the expression vector in the host-vector system of claim 8
`comprising growing cells of the host-vector system under conditions
`permitting production of the fusion polypeptide and recovering the
`fusion polypeptide. As described above, aflibercept is a fusion
`polypeptide encoded by the expression vector in the host-vector system
`of claim 8. Therefore, growing cells of the host-vector system under
`conditions permitting production of the encoded fusion polypeptide
`according to claim 11 will produce aflibercept. Thus, claim 11 is
`directed to a method of manufacturing aflibercept, the active ingredient
`of the approved product.
`
`Example 20 at col. 29, lines 13-29 of the '959 patent describes
`the construction of a nucleic acid (VEGFR1R2-Fc8Cl(a))encoding a
`fusion protein having the three components of aflibercept. The nucleic
`acid and amino acid sequence of VEGFR1R2-Fc8Cl(a) is provided in
`Figures 24A-C. See col. 9, lines 65-67. Thus, aflibercept is a fusion
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 6
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 7
`
`protein encoded by a nucleic acid sequence of SEQ ID NO: 15. The
`nucleotides encoding the various components of aflibercept are further
`described in Figures 24A-24C, whereby the Fltl lg domain 2 is encoded
`by nucleotide residues 80 through 389, the Flkl lg domain 3 is encoded
`by nucleotide residues 390 through 693 and the Fe component is
`encoded by nucleotide residues 694 through 1377.
`
`In addition, Example 20 at col. 29, lines 13-29, of the '959 patent
`describes the construction of the pVEGFR1R2-FcdCl(a) expression
`vector by insertion of DNA encoding amino acids SOT (corresponding to
`amino acids 27-29 of FIGS. 24A-24C) between Fltld2-Flkld3-FcdCl(a)
`amino acids 26 and 27 of FIGS. 21A-21C (GG) and removal of DNA
`encoding amino acids GPG corresponding to amino acids 229-231 of
`Figure 21B. As noted in Example 20, the SOT amino acid sequence is
`native to the Fltl receptor and was added back in to decrease the
`likelihood of heterogeneous N-terminal processing. The GPG (bridging
`sequence) was removed so that the Fltl and Flkl immunoglobulin
`domains were fused directly to one another. The complete DNA and
`deduced amino acid sequences of the pVEGFR1R2 FcdCl(a) chimeric
`molecule is set forth in FIGS. 24A-24C.
`
`The fusion polypeptide as described in the '959 patent was
`produced utilizing the cell culture system described in Example 21,
`column 29, lines 31-67 through column 30, lines 1-17. More
`particularly, suspension cultures of recombinant Chinese hamster ovary
`(CHO Kl/ElA) cells, which constitutively express the fusion
`polypeptide, were used to manufacture the fusion polypeptide. The
`cells were grown in bioreactors and the protein product was isolated
`and purified by affinity and size exclusion chromatography. The process
`is provided in greater detail in column 29, lines 48-58. The fusion
`polypeptide was harvested from the bioreactor using the process
`described in Example 22.
`
`Conclusion
`
`Because a method of manufacturing aflibercept meets all of the
`limitations of claim 11 of the '959 patent, and because aflibercept is the
`active ingredient of EYLEA™, the approved product, claim 11 of U.S.
`Patent No. 7,070,959 covers a method of manufacturing the approved
`product.
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 7
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 8
`
`10. Relevant Dates Under 35 U.S.C. § 156 for Determination of Applicable
`Regulatory Review Period[§ 1.740(a)(10)]
`
`(a)
`
`Patent Issue Date
`
`The '959 patent issued on July 4, 2006.
`
`(b)
`
`IND Effective Date [35 U.S.C. § 156(g}{l}{B)(i); 37 C.F.R. § 1. 740(a)(10)(i)(A)]
`
`The date that an exemption under§ 505(i) of the Federal Food, Drug and
`Cosmetic Act became effective (i.e., the date that an investigational new drug
`application ("IND") became effective) for EYLEA™ (referred to in the IND(cid:173)
`receipt letter as "Vascular Endothelial Growth Factor Fe Protein (human,
`recombinant, CHO cells, Regeneron)") was June 15, 2005. The application date
`for this IND was May 13, 2005. The IND was assigned number BB-IND#
`12462. A copy of the letter from the FDA reflecting the IN D's number, date of
`submission and date of receipt is provided in Attachment H.
`
`(c)
`
`BLA Submission Date [35 U.S.C § 156(g)(1)(BJ{i); 37 C.F.R.
`§ 1.740(a)(10)(i)(B)]
`
`The BLA was submitted on February 17, 2011 and received by the FDA on
`February 18, 2011, as shown in Attachment I. The BLA was assigned number
`BL 125387 /0.
`
`(d)
`
`BLA Issue Date [35 US.C § 156(g)(l)(B)(ii); 37 C.F.R. § 1. 740(a)(10}{i)(CJ]
`
`The FDA approved biologic license application 125387 /0 authorizing the
`marketing of EYLEA™ on November 18, 2011. EYLEA™ was approved under
`Department of Health and Human Services (DHHS) U.S. License No. 1760. A
`copy of the approval letter from the FDA is provided as Attachment C.
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 8
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 9
`
`11.
`
`Summary of Significant Events During Regulatory Review Period
`[§1.740(a)(11)]
`
`Pursuant to 37 C.F.R. § 1.740(a)(11), the following provides a brief description
`of the activities of Regeneron Pharmaceuticals, Inc., before the FDA in relation to the
`regulatory review of EYLEA™. The brief description lists the significant events that
`occurred during the regulatory review period for the approved product. In several
`instances, communications to or from the FDA are referenced. Pursuant to 37 C.F.R. §
`I. 740(a)(11), 21 C.F.R. § 60.20(a), and M.P.E.P. § 2753, copies of such communications
`are not provided in this application, but can be obtained from records maintained by
`the FDA.
`
`On May 13, 2005 Regeneron submitted to FDA an investigational new drug
`application for a recombinant fusion protein ( originally vascular endothelial growth
`factor Fe protein, now aflibercept) consisting of (a) a vascular endothelial growth
`factor (VEGF) receptor component having immunoglobulin-like (lg) domains
`consisting of an lg domain 2 of a first VEGF receptor that is human Flt1 and an lg
`domain 3 of a second VEGF receptor that is human Flk1; and (b) an Fe portion of
`human IgG1. The fusion protein was developed as a potential new therapeutic for
`intravitreal administration for treating (wet) age-related macular degeneration.
`
`On June 15, 2005, BB-IND #12462 became effective via a communication
`mailed to Regeneron on May 24, 2005, (see Attachment H). According to the
`FDA, initiation of trials could begin 30 days after May 16, 2005.
`
`From approximately July 2005 until approximately June 2008, a series of U.S.
`Phase I and II clinical trials were conducted. In addition, an extension trial is ongoing
`as of the date of this application.
`
`Between approximately July 2007 and July 2011, Phase III clinical trials
`were conducted. In addition, an extension trial is ongoing as of the date of this
`application.
`
`On June 1, 2009, representatives of Regeneron and CBER participated in a
`Type C meeting to seek agency agreement on the pharmacology /toxicology program
`for aflibercept.
`
`On September 15, 2009, representatives of Regeneron and CBER participated
`in a Type C meeting to review the status and development of pre-filled syringes as the
`intended container-closure device to support commercialization of aflibercept.
`
`On September 8, 2010, representatives of Regeneron and CBER participated in
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 9
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 10
`
`a Type 8 pre-BLA submission meeting to discuss and review clinical results of trials
`conducted prior to that date.
`
`On September 27, 2010, representatives of Regeneron and CBER participated
`in a Type B pre-BLA submission meeting to discuss information and requirements for
`the chemical, manufacturing and control (CMC) chapter of the BLA.
`
`On April 15, 2011, FDA granted priority review for aflibercept for AMO.
`
`On November 18, 2011, FDA approved BLA No. BL 125387 /0, issuing
`marketing authorization for EYLEA™. (See Attachment C.)
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 10
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 11
`
`12. Statement Concerning Eligibility for and Duration of Extension Sought Under
`35 U.S.C. § 156 (37 C.F.R § 1.740(a)(12)]
`
`(a) In the opinion of the Applicant, U.S. Patent No. 7,070,959 is eligible for an
`extension under§ 156 because:
`
`(i) one or more claims of the '959 patent claim a method of manufacturing the
`approved product;
`
`(ii) the term of the '959 patent has not been previously extended on the basis
`of§ 156;
`
`(iii) the '959 patent has not expired;
`
`(iv) no other patent has been extended pursuant to§ 156 on the basis of the
`regulatory review process associated with the approved product, EYLEA™;
`
`(v) there is an eligible period of regulatory review by which the patent may be
`extended pursuant to § 156;
`
`(vi) the applicant for marketing approval exercised due diligence within the
`meaning of§ 156(d)(3) during the period ofregulatory review;
`
`(vii) the present application has been submitted within the 60-day period
`following the approval date of the approved product, pursuant to§ 156(c); and
`
`(viii) this application otherwise complies with all requirements of 35 U.S.C.
`§ 156 and applicable rules and procedures.
`
`(b) The period by which the term of the '959 patent is requested by Applicant to be
`extended is 1118 days.
`
`(c) The requested period of extension of term for the '959 patent corresponds to the
`regulatory review period that is eligible for extension pursuant to §156, based on the
`facts and circumstances of the regulatory review associated with the approved
`product EYLEA ™. The period was determined as follows.
`
`(i) The relevant dates for calculating the regulatory review period, based on
`the events discussed in the section above, are the following.
`
`Exemption under FDCA § 505(i) became effective June 15, 2005 (30 days after
`FDA receipt of the IND on May 16, 2005)
`
`Patent was granted July 4, 2006
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 11
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 12
`
`Biologics License Application (BLA) under PHSA § 351 was filed February 17,
`2011
`
`BLA was approved November 18, 2011
`
`(ii) The '959 patent was granted during the period specified in
`§156(g)(1)(B)(i) (i.e., the period from the date of the grant of the exemption under
`§ 505(i) of the FDCA until the date of submission of the BLA). Pursuant to§ 156(b)
`and (c)(2 ), the calculated regulatory review period includes a component equal to
`half of the number of days within that period that are after the grant of the patent
`(1/2 of 1688, or 844 days).
`
`(iii) Because the patent was granted before the start of the period specified in §
`156(g)(l)(B)(ii) (i.e., the period from the date of submission of the BLA until the date
`of approval), the regulatory review period under§ l56(b) includes a component equal
`to the total number of days in that period (274 days).
`
`(iv) The '959 patent will expire on May 23, 2020 taking into account the
`Terminal Disclaimer (See Attachment E).
`
`(v) Taking into account the 844 days specified in (ii) above, which accounts for
`the time period between the date of grant of the exemption under§ 505(i) of the
`FDCA until the date of submission of the BLA), and further pursuant to§ l56(b) and
`(c)(2 ), whereby the calculated regulatory review period includes a component equal
`to half of the number of days within that period that are after the grant of the patent,
`plus the 274 days specified in the regulatory review period under§ l56(b) and noted
`in (iii) above, which includes the number of days from the date of submission of the
`BLA until the date of approval, the total number of days to be included for
`consideration of patent term extension is believed to be 1118 days.
`
`(vi) The date of approval of the approved product is November 18, 2011.
`
`(vii) The date that is fourteen years from the date of approval of the approved
`product is November 18, 2025.
`
`(viii) The addition of 1118 days to the time of patent expiry (which includes
`the period disclaimed via the terminal disclaimers) brings the projected patent expiry
`date to June 15, 2023. The date until the end of the fourteen-year period specified in
`§156 (c)(3) is November 18, 2025. Accordingly, the projected date of expiration
`taking into account the 1118 day patent term extension does not exceed the date
`projected to be 14 years beyond the date of BLA approval. As such, the period by
`which the patent may be extended is not limited by the fourteen-year rule of§
`156(c)(3).
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 12
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 13
`
`(ix) The '959 patent issued after the effective date of Public Law No. 98-417.
`As such, the two- or three -year limit of 35 U.S.C. § l56(g)(6)(C) does not apply.
`
`13. Statement Pursuant to 37 C.F.R. § 1.740(a)(13)
`
`Pursuant to 37 C.F.R. § 1.740(a)(13), Applicant acknowledges its duty to
`disclose to the Director of the PTO and to the Secretary of Health and Human Services
`any information which is material to the determination of entitlement to the
`extension sought, particularly as that duty is defined in 37 C.F.R. § 1.765. In
`furtherance of this duty, Applicant wishes to inform the Director and Secretary that
`concurrently with the present Application for Extension of Patent Term Under 35
`U.S.C. §156 Applicant has filed an Application for Extension of Patent Term Under 35
`U.S.C. §156 (plus two copies) in connection with U.S. Patent Nos. 7,374,757 and
`7,374,758.
`
`14. Applicable Fee[§ 1.740(a)(14)]
`
`Please deduct all fees necessary pursuant to 37 C.F .R. §1.20(j) corresponding
`to the fee for a patent term extension application under 35 U.S.C. § 156 from deposit
`account no. 18-0650. Please deduct any additional fee or fees deemed necessary in
`excess of this amount from our deposit account no. 18-0650.
`
`15. Name and Address for Correspondence[§ 1.740(a)(15)]
`
`Please direct all inquiries, questions, and communications regarding this
`application for term extension to :
`
`Valeta Gregg, Ph.D., J.D.
`Vice President and Assistant General Counsel, Patents
`Regeneron Pharmaceuticals, Inc.
`777 Old Saw Mill River Rd.
`Tarrytown, NY 10591-6707
`Tel. 914-847-1077
`Fax 914-847-7705
`email: valeta.gregg@regeneron.com
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 13
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 14
`
`Two additional copies of this application are enclosed, in compliance with 37
`C.F.R.§ I. 7 40(b ).
`
`Sincerely,
`
`v;J~~
`
`Attorney/ Agent for Applicant
`Registration NR, 35,127
`Dated: s9, / .J::le_c c:x.. o If
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 14
`
`

`

`U.S. Patent No. 7,070,959
`Papadopoulos, et al.
`Application Under 35 U.S.C. § 156
`
`Page 15
`
`Index of Attachments
`
`Attachment A - Copy of Assignments of U.S. Patent No. 7,070,959
`
`Attachment B- Copy of EYLEA™ Product Label
`
`Attachment C - Copy of EYLEATM BLA Approval letter from the FDA
`
`Attachment D - Copy of U.S. Patent No. 7,070,959
`
`Attachment E - Copy of Terminal Disclaimer for U.S. Patent No. 7,070,959
`
`Attachment F - Copy of Maintenance Fee Statement for U.S. Patent No. 7,070,959
`
`Attachment G - Copy of Holash et al. PNAS 99(17):11393-11398 (2002)
`
`Attachment H - Copy of IND-receipt letter from FDA
`
`Attachment I - Copy of BLA Submission ac~nowledgement letter from FDA
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 15
`
`

`

`' "
`
`.
`
`ATTACHMENT A
`
`Copy of Assignment of U.S. Patent No.
`
`7,070,959
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 16
`
`

`

`O \Pc
`""o\
`~ r--~~-;,':.-_ - - - -
`Re
`
`I :
`
`i~o-1595
`
`'
`~,m ~y
`
`OB · 21 2001
`/11/lfililll/f 1
`101A1.7994
`To the Honorable Commissioner of Patents and Trademarks: Please recora me attached original documents or copy thereof.
`
`.4t J)
`
`U.S. Department of Commerce
`Patent and Trademark Office
`
`1. Name of conveying party(ies):
`~-/3'6/
`
`Nicholas J. Papadopoulos
`Samuel Davis
`George D. Yanacopoulos
`
`2. Name and address of receiving party(ies):
`Name: Regeneron Pharmaceuticals, Inc.
`
`Internal Address: _ _ _ _ _ _ _ _ _ _ ____.
`
`City: Tarrytown, State:_NY_ Zip: 10591
`
`Additional name(s) of conveying party(ies)
`attached? (cid:143) Yes 11J No
`Street Address: 777 Old Saw Mill River Road
`+-------------------1
`3. Nature of conveyance:
`(cid:143)
`KJ Assignment
`Merger
`(cid:143) Security Agree!-Tlent (cid:143) Change of Name
`D Other _ _ _ _ _ _ _ _ _ _ _
`Execution Date: June 1, 2001
`
`Additional name(s) & address(es) attached?
`D
`
`IX) No
`
`Yes
`
`4. Application number{s) or patent number(s):
`
`I
`
`If this document is being filed together with a new application, the execution date of the application is: -------1
`A. Patent Application No:(s)
`B. Patent No.(s)
`
`PCT/US00/14142
`
`Additional numbers attached?
`
`(cid:143) Yes No Ix!
`
`S. Name and address of party to whom corre(cid:173)
`spondence concerning document should be
`mailed:
`Name: __ L_i_n_da_O_. _P_a __ lla_di_._no _ _ _ _ _ _ -----1
`Internal Address: Regeneron Pharmaceuticals,
`Inc.
`
`6. Total number of applications and patents
`involved: I 1
`I
`
`7. Total fee (37 CFR 3.41): .... $.::tlL. An.lJU..nn _ _ ____.
`Iii Enclosed
`(cid:143) Authorized to be charged to deposit account
`
`Street Address:777 ('\IA C'nn 11.,f:ll n,., __ n--..J
`
`8. Deposit account number:
`18-0650
`
`City: Tarrytown,
`
`State: NY Zip: 10591
`DO NOT USE rms SPACE
`
`9. Statement and signature.
`To the best of my knowledge and beliet the foregoing iriformation ts true and correct and any attached copy is a
`,
`true copy of the original document.
`
`•
`. /) .
`,0!
`~/tin /"; 1121 l I/~. il.JU' August 9, 2001
`Slg¢zture
`Date
`/
`
`Total number of pages comprising cover sheet: [!J
`
`Linda O. Palladino \
`
`8/20/2001 I OH11
`1 f'C:581
`
`00000105 PCTUS0014142
`40.00 DP
`
`~
`
`0 Name of Person Signing
`
`_ /
`
`PATENT
`REEL: 012Q17_fRAME: 0978
`
`Mylan Exhibit 1102
`Mylan v. Regeneron, IPR2021-00880
`Page 17
`
`

`

`Att. Docket No. REG 710-A-PCT
`
`ASSIGNMENT
`
`WHEREAS, We, Nicholas J. Papadopoulos, residing at 59 Heritage Lane, LaGrangeville,
`New York 12540, a citizen of the United States of America; Samuel Davis, residing at 332 West
`88th Street, Apt. #B2, New York, New York 10024, a citizen of The United States of America; and
`George D. Yancopoulos, residing at 1519 Baptist Church Road, Yorktown Heights, New York
`10598_ at, a citizen of the United States of America (HEREINAFTER CALLED "ASSIGNORS")
`are inventor(s) of the invention(s) disclosed and/or claimed in the following patent application:
`
`PCT/US00/14142 filed May 23, 2000; and
`
`WHEREAS, REGENERON PHARMACEUTICALS INC., a corporation organized and
`existing under the laws of the State of New York, with offices at 777 Old Saw Mill River Road,
`Tarrytown, New York 10591-6707, U.S.A. (HEREINAFTER called "ASSIGNEE") is desirous of
`acquiring our entire right, tide and interest in, to, and under the said applications;
`
`NOW, THEREFORE, in consideration of the sum of One Dollar ($1.00) to us in hand
`paid, and other good and valua,.~le consideration, the receipt of which is hereby acknowledged,
`We, the said ASSIGNORS, have sold, assigned, transferred and set over, and by these presents do
`hereby sell, assign, transfer and set over unto the said ASSIGNEE. its successors, legal
`representatives, and assigns, our entire right, title and interest for all countries in and to any and all
`inventions which are disclosed and claimed, and any and all inventions which are disclosed but
`not claimed in the above-described United States app1ications, and in and to said United States
`Applications and all divisions, renewals, continuations, and continuations-in-part thereof, and all
`Patents of the United States which may be granted thereon and all reissu~s and extensions thereof;
`and all applications for industrial property protection, including, without limitation, all
`applications for patents utility models, and designs which may hereafter be filed for said
`inventions in any country or countries foreign to the United States, together with the right to file
`such applications and the right to claim for the same the priority rights derived from said United
`States applications under the Patent Laws of the United States, the International Convention of
`1883 and later modifications thereof, under the Patent Cooperation Treaty, under the European
`Patent Convention, or under any other