I.
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Docket No.: 029420.0155-USOI
`
`(PATENT)
`
`In re Patent Application of:
`Alan J. Korman, et a].
`
`US. Patent No.: 6,984,720
`
`Issued: January 10, 2006
`
`For: HUMAN CTLA-4 ANTIBODIES
`
`.
`
`v
`
`TRANSMITTAL LETTER
`
`MS Hatch-Waxman PTE
`Commissioner for Patents
`
`Office of Patent Legal Administration
`Room MDW 7D55
`
`600 Dulany Street (Madison Building)
`Alexandria, VA 22314
`
`Dear Sir:
`
`RECEIVED
`MAY 16'3‘20“
`EXTENSION
`PATENTOPLA
`
`DC13981872-l
`
`Enclosed are the following items for filing in connection with the above-referenced
`
`Patent Application:
`
`1.
`
`Fee Transmittal;
`
`Request for Extension of Patent Term Under 35 U.S.C. § 156 together with
`
`Exhibits 1-8 (original plus two copies);
`
`Request for Extension of Patent Term Under 35 U.S.C. § 156 without Exhibits
`
`(for fee purposes); and
`
`68/23/2811 RLOGRN
`
`88883385 589746
`
`39544668
`
`4. Return receipt postcard.
`
`61 FEMS?
`
`1128'” m
`
`Please charge our Deposit Account No. 50-0740 in the amount of $1,120.00 to cover
`
`the required fees. The Director is hereby authorized to charge any deficiency in the fees filed,
`
`'
`
`Mylan v. Genentech
`IPR2016-00710
`Merck Ex. 1135, Pg. 1
`
`

`

`A P
`
`atent N0.: 6,984,720
`
`Docket N0.: 029420.0155—USOI
`
`this application by this firm) to our Deposit Account No. 50-0740, under Docket No.
`
`029420.0155—USOI. A duplicate copy of this paper is attached.
`
`It is not believed that extensions of time or fees for net addition of claims are required
`
`asserted to be filed or which should have been filed herewith (or with any paper hereafier filed in
`
`(202) 662—6000
`
`beyond those that may otherwise be provided for in documents accompanying this paper.
`
`However, if additional extensions of time are necessary to prevent abandonment of this
`
`application, then such extensions of time are hereby petitioned, and any fees required therefor
`
`(including fees for net addition of claims) are hereby authorized to be charged to our Deposit
`
`Account No. 50-0740.
`
`Dated: May 16, 2011
`
`Respectfully submitted,
`
`Paul J. Berman
`
`»
`
`Registration N0.: 36,744
`Natalie M. Derzko
`
`Registration N0.: 48,102
`COVINGTON & BURLING LLP
`
`1201 Pennsylvania Avenue, NW
`Washington, DC 20004-2401
`
`Merck Ex. 1135, Pg. 2
`
`

`

`PTO/SB/17 (10-08)
`Approved tor use through 09/30/2010 0MB 0651-0032
`U.S. Patent and Trademark Office; US DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act 0! 1995, no person are required to respond to a collection of information unless it displays a valid OMB control number
`
`Effective on 12/03/2004,
`eonsvidamwmmms).
`FEE TRANSMITTAL
`
`F°' FY 2°09
`
`METHOD OF PAYMENT (check all that apply)
`
`AtanJ. Konnan
`Nomppncame
`
`029420-o1ss-usm
`
`Application Type
`Utility
`Design
`Plant
`Reissue
`Provisional
`2. EXCESS CLAIM FEES
`
`.
`
`-
`
`SEARCH FEES
`Small Entity
`Fee m
`270
`50
`165
`270
`0
`
`Fee
`540
`100
`330
`540
`0
`
`Fee (fl
`330
`220
`220
`330
`220
`
`MM '
`Each claim over 20 (including Reissues)
`Each independent claim over 3 (including Reissues)
`Multiple dependent claims
`Total Claims
`Extra Claims
`
`Fee (3)
`
`x
`‘ 203' HP
`HP = highest number of total claims paid for. it greater than 20.
`
`=
`
`Fee Paid (5)
`
`lndep. Claims
`
`Extra Claims
`
`Fee (3)
`
`X
`
`Fee Paid (S)
`
`Fees Paid |§)
`
`EXAMINATION FEES
`Small Entity
`Fee m
`110
`70
`85
`
`Fee (fl
`220
`140
`170
`650
`0
`
`Small Entig
`
`_
`
`mm mm
`52
`26
`220
`1 10
`390
`195
`Multiple Dependent Claims
`Fee m
`Fee Paid (fl
`
`-
`
`‘
`
`1
`
`Fee (fl
`
`Fee Paid ($1
`
`=
`- 3 or HP =
`HP = highest number of independent claims paid tor, It greater than 3.
`3. APPLICATION SIZE FEE
`If the specification and drawings exceed 100 sheets of paper (excluding electronically filed sequence or computer
`listings under 37 CFR 1.52(e)), the application size fee due is $270 ($135 for small entity) for each additional 50
`sheets or fraction thereof. See 35 U.S.C. 41(a)(l)(G) and 37 CFR l.l6(s).
`Total Sheets
`Extra Sheets
`N mb r of each additional 50 or fraction thereof
`(round up to a whole number) x
`
`E] Check El Credit Card El Money Order D None D Other (please identify):
`Covington 8: Burling LLP
`12] Deposit Account
`Deposit Account Number:
`50-0740
`Deposilecount Name;
`For the above-identified deposit account. the Director is hereby authorized to: (check all that apply)
`[x] Charge fee(s) indicated below
`l:| Charge fee(s) indicated below. except for the filing fee
`Charge any additional fee(s) or underpayments of
`E] Credit any ovemayments
`fee(s) under 37 CFR 1.16 and 1.17
`FEE CALCULATION
`1. BASIC FILING, SEARCH. AND EXAMINATION FEES
`FILING FEES
`Small Entig
`Fee [5)
`165
`110
`110
`165
`110
`
`May 16.2011
`
`150 =
`
`-100 =
`4. OTHER FEElS)
`Non-English Specification, $130 fee (no small entity discount)
`Other (e.g., late filing surcharge): 1457 Extension of term of atent
`1,120.00
`I“l—rSUBMITTED BY . .
`
`
`
`
`
`
`
`Natalie M. Derzko
`
`)
`
`Date
`
`Fees Paid (fl
`
`Merck Ex. 1135, Pg. 3
`
`

`

`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Docket No.: 029420.0155-USOl
`
`(PATENT)
`
`In re United States Patent of:
`
`Alan J. Korrnan, et al.
`
`Patent No.: 6,984,720
`
`Issued: January 10, 2006
`
`For: HUMAN CTLA-4 ANTIBODIES
`
`Mail Stop Hatch-Waxman PTE
`Commissioner for Patents
`
`Office of Patent Legal Administration
`Room MDW 7D55
`
`600 Dulany Street (Madison Building)
`Alexandria, VA 22314
`
`REQUEST FOR EXTENSION OF PATENT TERM UNDER
`35 U.S.C. §156
`
`DC: 398372l-l
`
`Pursuant to 35 U.S.C. §156 and 37 C.F.R. §§1 .710-l.791, Medarex, Inc., the
`
`current address of which is Route 206 and Province Line Road, Princeton, New Jersey 08540
`
`(“Applicant” or “Medarex”), hereby requests an extension of US. Patent No. 6,984,720 (the
`
`“’720 patent”). As permitted by 37 CPR. §1.785(b) and MPEP §2761, Applicant is
`
`concurrently filing a request for patent term extension of US. Patent No. 7,605,238 based upon
`
`the same regulatory review period.
`
`Medarex represents that it is the owner and assignee of the entire interest in and to
`
`Letters Patent of the United States No. 6,984,720 (Exhibit 1) granted to Alan J. Korman, Edward
`
`L. Halk, Nils Lonberg, Yashwant M. Deo and Tibor P. Keler (the “inventors”) on January 10,
`
`2006, for “Human CTLA-4 Antibodies” by virtue of an assignment from the inventors to
`
`Medarex, recorded in the United States Patent and Trademark Office (“PTO”) on May 18, 2001
`
`Merck Ex. 1135, Pg. 4
`
`

`

`Patent No.: 6,984,720
`
`- 2 -
`
`Docket No.: 029420.00155-USOI
`
`at Reel 011817, Frame 0279 (Exhibit 2). The ‘720 patent matured from US. Patent Application
`
`No. 09/644,668, filed on August 24, 2000, which claims the benefit of US. Provisional Patent
`
`Application No. 60/150,452, filed on August 24, 1999, now expired.
`
`The approved product that is relevant to this Request is YERVOYTM
`
`(ipilimumab) Injection, for intravenous infusion, referred to herein as “YERVOY” or “Approved
`
`Product.”
`
`The Marketing Applicant for YERVOY is Bristol-Myers Squibb Company
`
`(“BMS’), Medarex is a wholly-owned subsidiary of EMS and is authorized to rely upon the
`
`activities of BMS, its predecessors, and affiliates for purposes of this patent term extension
`
`the rules for extension of patent term issued by the PTO at 37 C.F.R. Subpart F, §§1 .710 to 1.791
`
`acids. The amino acid sequence for YERVOY is as follows.
`
`application.
`
`The following information is submitted in accordance with 35 U.S.C. §156(d) and
`
`and follows the numerical format set forth in 37 CPR. §1.740:
`
`(1)
`
`A COMPLETE IDENTIFICATION OF THE APPROVED PRODUCT
`
`AS BY APPROPRIATE CHEMICAL AND GENERIC NAME, PHYSICAL STRUCTURE OR
`
`CHARACTERISTICS:
`
`The approved product is YERVOY, an injection for intravenous infusion of the
`
`active ingredient ipilimumab, available in two dosage forms namely, 50 mg/ 10 ml (5 mg/mL)
`
`and 200 mg/40 mL (5 mg/mL). YERVOY has been approved for the treatment of unresectable
`
`or metastatic melanoma (approved labeling attached as Exhibit 3). YERVOY is a human
`
`cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody that is comprised of 1,326 amino
`
`Merck Ex. 1135, Pg. 5
`
`

`

`Patent No.: 6,984,720
`
`Docket No.: 029420.00155-USOI
`
`
`
`Antibody Amino Acid Sequence**
`Se ment
`
`QVQLVESGGGVVQPGRSLRLSCAASGFTFS
`SYTMH
`
`CDR2
`
`WVRQAPGKGLEWVT
`FISYDGNNKYYADSVKG
`
`RFTISRDNSKNTLYLQMNSLRAEDTAIYYCAR
`
`
`TGWLGPFDY
`
`WGQGTLVTVSS
`ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW
`
`13, 2011.
`
`
`EIVLTQSPGTLSLSPGERATLSC
`
`RASQSVGSSYLA
`WYQQKPGQAPRLLIY
`GAFSRAT
`GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC
`QQYGSSPWT
`FGQGTKVEIK
`RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW
`Light
`KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
`Chain
`Constant KVYACEVTHQGLSSPVTKSFNRGEC
`Region
`
`FR4
`
`Chain
`
`FRI
`CDRl
`
`CDR3
`
`NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
`NVNHKPSNTKVDKRV
`EPKSCDKTHTCPPCPAPELLG
`GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
`
`YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG
`KEYKCKVSNKALPAPIEKTISKAK
`
`GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW
`ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
`VFSCSVMHEALHNHYTQKSLSLSPGK
`
`
`
`* * The one-letter amino acid code used in the table follows the nomenclature
`
`developed by the International Union of Pure and Applied Chemistry (IUPAC)
`and the International Union of Biochmistry and Molecular Biology (IUB) in the
`IUPAC-IUB Joint Commission on Biochemical Nomenclature (J CBN),
`“Nomenclature and Symbolism for Amino Acids and Peptides,” 1983. See
`http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html#AA1, visited May
`
`Merck Ex. 1135, Pg. 6
`
`

`

`Patent No.2 6,984,720
`
`— 4 —
`
`Docket N0.: 029420.00155-USOl
`
`(2)
`
`A COMPLETE IDENTIFICATION OF THE FEDERAL STATUTE
`
`INCLUDING THE APPLICABLE PROVISION OF LAW UNDER WHICH THE
`
`REGULATORY REVIEW OCCURRED:
`
`The Approved Product is a drug product that was approved under section 351 of
`
`the Public Health Service Act (PHSA) (42 U.S.C. §262).
`
`COMMERCIAL MARKETING OR USE (EITHER ALONE OR IN COMBINATION WITH
`
`STATEMENT THAT IT HAS NOT BEEN PREVIOUSLY APPROVED FOR COMMERCIAL
`
`(3) AN IDENTIFICATION OF THE DATE ON WHICH THE PRODUCT
`
`RECEIVED PERMISSION FOR COMMERCIAL MARKETING OR USE UNDER THE
`
`PROVISION OF LAW UNDER WHICH THE APPLICABLE REGULATORY REVIEW
`
`PERIOD OCCURRED:
`
`The Approved Product received permission for commercial marketing or use by
`
`the United States Food and Drug Administration (FDA) pursuant to section 35 1 (a) of the PHSA
`
`(42 U.S.C. § 262(3)) in a letter dated March 25, 2011. A copy of the approval letter is attached
`
`as Exhibit 4.
`
`(4) IN THE CASE OF A DRUG PRODUCT, AN IDENTIFICATION OF EACH
`
`ACTIVE INGREDIENT IN THE PRODUCT AND AS TO EACH ACTIVE INGREDIENT, A
`
`MARKETING OR USE UNDER THE FEDERAL FOOD, DRUG AND COSMETIC ACT,
`
`THE PUBLIC HEALTH SERVICE ACT, OR THE VIRUS-SERUM-TOXIN ACT OR A
`
`STATEMENT OF WHEN THE ACTIVE INGREDIENT WAS APPROVED FOR
`
`Merck Ex. 1135, Pg. 7
`
`

`

`Patent No.: 6,984,720
`
`— 5 -
`
`Docket No.: 029420.00155-USOI
`
`OTHER ACTIVE INGREDIENTS), THE USE FOR WHICH IT WAS APPROVED, AND THE
`
`PROVISION OF LAW UNDER WHICH IT WAS APPROVED: (37 CPR § 1.740(a)(4))
`
`The active ingredient in YERVOY is ipilimumab. Ipilimumab is comprised of
`
`1,326 amino acids and has an amino acid sequence as noted earlier in section (1) of this Request.
`
`YERVOY is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody that has
`
`been approved under section 351(a) of the PHSA for the treatment of unresectable or metastatic
`
`melanoma.
`
`Ipilimumab has not been previously approved for commercial marketing or use
`
`under the Federal Food, Drug, and Cosmetic Act, the PHSA, or the Virus-Serum-Toxin Act.
`
`A STATEMENT THAT THE APPLICATION IS BEING SUBMITTED
`
`NUMBER, THE DATE OF ISSUE, AND THE DATE OF EXPIRATION:
`
`'
`
`(5)
`
`WITHIN THE SIXTY DAY PERIOD PERMITTED FOR SUBMISSION PURSUANT TO
`
`SECTION 1.720(f) AND AN IDENTIFICATION OF THE DATE OF THE LAST DAY ON
`
`WHICH THE APPLICATION COULD BE SUBMITTED:
`
`This Request is timely filed, pursuant to 35 U.S.C. § 156(d)(1), within the
`
`permitted sixty-day (60-day) period that began on March 25, 2011, when the product received
`
`permission for commercial marketing or use under section 351(a) of the PHSA and that will
`
`expire on May 24, 2011. Applicant understands that, pursuant to 37 C.F.R. § 1.720(f), the PTO
`
`may deem this period to expire one day earlier, on May 23, 2011.
`
`(6)
`
`A COMPLETE IDENTIFICATION OF THE PATENT FOR WHICH AN
`
`EXTENSION IS BEING SOUGHT BY THE NAME OF THE INVENTOR, THE PATENT
`
`Merck Ex. 1135, Pg. 8
`
`

`

`Patent No.: 6,984,720
`
`- 6 -
`
`Docket N0.: 029420.00155-US01
`
`UNITED STATES PATENT N0.: 6,984,720
`
`INVENTORS:
`
`DATE OF ISSUE: JANUARY 10, 2006
`
`EXPIRATION DATE: AUGUST 2, 2022
`
`ALAN J. KORMAN
`EDWARD L. HALK
`NILS LONBERG
`YASHWANT M. DEO
`TIBOR P. KELER
`
`ISSUED IN THE PATENT:
`
`The expiration date of U.S. Patent No. 6,984,720 (“the ‘720 patent”) is August 2,
`
`2022, based on the following information. The patent application that issued as the ‘720 patent,
`
`U.S. Patent, Application No. 09/644,668 (“the ‘668 application”), was filed on August 24, 2000,
`
`and claims the benefit U.S. Provisional Patent Application No. 60/150,452, filed on August 24,
`
`1999, now expired. Without a patent term adjustment, the expiration of the ‘720 patent would be
`
`August 24, 2020; however, as noted on its face, the ‘720 patent is entitled to a patent term
`
`adjustment pursuant to 35 U.S.C. §154 of 708 days, bringing the expiration of the ‘720 patent to
`
`August 2, 2022.
`
`(7)
`
`A COPY OF THE PATENT FOR WHICH AN EXTENSION IS BEING
`
`SOUGHT, INCLUDING THE ENTIRE SPECIFICATION (INCLUDING CLAIMS) AND
`
`DRAWINGS:
`
`A complete copy of U.S. Patent No. 6,984,720 is attached as Exhibit 1.
`
`(8)
`
`A COPY OF ANY DISCLAIMER, CERTIFICATE OF CORRECTION,
`
`RECEIPT OF MAINTENANCE FEE PAYMENT, OR RE-EXAMINATION CERTIFICATE
`
`Merck Ex. 1135, Pg. 9
`
`

`

`Patent No.: 6,984,720
`
`- 7 -
`
`Docket No.2 029420.00155-USOI
`
`No terminal disclaimer or certificate of correction has been filed in US. Patent
`
`No. 6,984,720 (“the ‘720 patent”). Moreover, the ‘720 patent has not been reexamined, and so
`
`no re—examination certificate has been issued in US. Patent No. 6,984,720.
`
`The first maintenance fee for the ‘720 patent was paid on July 10, 2009, as shown
`
`by the attached Patent Bibliographic Sheet obtained from Public PAIR on May 13, 2011 and the
`
`USPTO Maintenance Fee Statement for this patent obtained from Public PAIR on May 13, 2011,
`
`both found in Exhibit 5.
`
`Accordingly, there are no unpaid maintenance fees for the ‘720 patent.
`
`set forth in SEQ ID NOS:24, 29 and 35.
`
`2. An antibody comprising: (a) a heavy chain variable amino acid sequence
`having the amino acid sequence set forth in SEQ ID NO: 1 7; and (b) a light chain
`variable amino acid sequence having the amino acid sequence set forth in SEQ ID
`NO:7, wherein the antibody is capable of binding human CTLA4.
`
`(9)
`
`A STATEMENT THAT THE PATENT CLAIMS THE APPROVED
`
`PRODUCT, OR A METHOD OF USING OR MANUFACTURING THE APPROVED
`
`PRODUCT, AND A SHOWING WHICH LISTS EACH APPLICABLE PATENT CLAIM
`
`AND DEMONSTRATES THE MANNER IN WHICH AT LEAST ONE SUCH PATENT
`
`CLAIM READS ON THE APPROVED PRODUCT OR A METHOD OF USING OR
`
`MANUFACTURING THE APPROVED PRODUCT:
`
`US. Patent No. 6,984,720 claims the Approved Product. At least claims 2, 4 and
`
`7, 8 and 10 read on the Approved Product. These claims are set forth below.
`
`***
`
`4. An antibody capable of binding human CTLA4, which antibody comprises: (a)
`a heavy chain variable region having CDR sequences set forth in SEQ ID
`NOS:27, 32 and 37; and (b) a light chain variable region having CDR sequences
`
`Merck Ex. 1135, Pg. 10
`
`

`

`Patent No.: 6,984,720
`
`Docket No.: 029420.00155-USOI
`
`7. An antibody capable of binding human CTLA4, which antibody comprises: (a)
`a heavy chain variable region of a human VH 3-303 gene; and (b) a light chain
`variable region of a human VK A-27 gene.
`
`8. An antibody according to claim 7, wherein the antibody is capable of binding
`human CTLA4 with a binding affinity of about 108 M" or greater.
`
`***
`
`10. An antibody according to claim 7, wherein the antibody inhibits binding of the
`human CTLA4 to B7—l or to B7-2.
`
`Pursuant to 37 C.F.R. § l.740(a)(9), a showing which demonstrates the manner in
`
`which one claim reads on the Approved Product is set forth herein below.
`
`euence comiled from these regions
`
`Ipilimumab comprises a heavy chain variable
`amino acid sequence composed of three
`complementarity determining regions (CDRS)
`and four framework regions (FRs) arranged as
`follows: FRI, CDRl, FR2, CDR2, FR3,
`CDR3, FR4, as set forth immediately under
`“Heavy Chain” in section (1) of this Request.
`The amino acid sequence compiled from these
`regions identified in section (1) of this Request
`has the amino acid sequence set forth in SEQ
`ID NO: 17 of the ‘720 Patent.
`
`2. An antibody comprising:
`
`The A proved Product
`Ipilimumab (the ‘active ingredient in
`YERVOYTM) is an antibody.
`
`(a) a heavy chain variable amino acid sequence
`having the amino acid sequence set forth in
`SEQ ID NO:l7; and
`
`(b) a light chain variable amino acid sequence
`having the amino acid sequence set forth in
`SEQ ID NO:7,
`
`Ipilimumab comprises a light chain variable
`amino acid sequence composed of three CDRs
`and four FRs arranged as follows: FRI ,
`CDRl, FRZ, CDR2, FR3, CDR3, FR4, as set
`
`forth immediately under “Light Chain” in
`section (1) of this Request. The amino acid
`
`Merck Ex. 1135, Pg. 11
`
`

`

`wherein the antibody is capable of binding
`human CTLA4.
`
`Ipilimumab is capable of binding human
`
`Patent No.: 6,984,720
`
`Docket No.: 029420.00155-USO]
`
`identified in section (1) of this Request has the
`amino acid sequence set forth in SEQ ID NO:7
`of the ‘720 patent.
`
`CTLA4.
`
`Merck Ex. 1135, Pg. 12
`
`

`

`Patent No.: 6,984,720
`
`Docket No.: 029420.00155-USOI
`
`(10)
`
`A STATEMENT BEGINNING ON A NEW PAGE OF THE
`
`RELEVANT DATES AND INFORMATION PURSUANT TO 35 U.S.C. §156(g) IN ORDER
`
`TO ENABLE THE SECRETARY OF HEALTH AND HUMAN SERVICES OR THE
`
`SECRETARY OF AGRICULTURE, AS APPROPRIATE, TO DETERMINE THE
`
`APPLICABLE REGULATORY REVIEW PERIOD AS FOLLOWS:
`
`(i) FOR A PATENT CLAIMING A HUMAN DRUG, ANTIBIOTIC, OR
`
`HUMAN BIOLOGICAL PRODUCT, THE EFFECTIVE DATE OF THE INVESTIGATIONAL
`
`NEW DRUG APPLICATION (IND) AND THE IND NUMBER; THE DATE ON WHICH A
`
`NEW DRUG APPLICATION (NDA) OR A PRODUCT LICENSE APPLICATION (PLA)
`
`WAS INITIALLY SUBMITTED AND THE NDA OR PLA NUMBER; AND THE DATE ON
`
`WHICH THE NDA WAS APPROVED OR THE PRODUCTS LICENSE ISSUED:
`
`An original investigational new drug application (“IND”) was submitted by
`
`Medarex, Inc., now a wholly-owned subsidiary of Bristol-Myers Squibb Co. (“BMS”), on July
`
`12, 2000 and was received by FDA on July 13, 2000. A copy of FDA’s acknowledgement letter
`
`is provided at Exhibit 6. The FDA assigned BB-IND No. 9186 to this IND, which became
`
`effective 30 days after FDA’s receipt date, namely, on August 12, 2000.
`
`A biologics license application (“BLA”) was submitted by EMS on June 25, 2010
`
`and acknowledged as received on this date in a letter from FDA dated July 8, 2010 (Exhibit 7).
`
`was approved on March 25, 2011 (Exhibit 4).
`
`The Submission Tracking Number (STN) assigned to this BLA was BL 125377/0. The BLA
`
`Merck Ex. 1135, Pg. 13
`
`

`

`Patent No.: 6,984,720
`
`- 11 -
`
`'
`
`Docket No.: 029420.00155-USOI
`
`(11)
`
`A BRIEF DESCRIPTION BEGINNING ON A NEW PAGE OF THE
`
`SIGNIFICANT ACTIVITIES UNDERTAKEN BY OWNER, THE MARKETING
`
`APPLICANT, DURING THE APPLICABLE REGULATORY REVIEW PERIOD WITH
`
`RESPECT TO THE APPROVED PRODUCT AND THE SIGNIFICANT DATES
`
`APPLICABLE TO SUCH ACTIVITIES:
`
`In accordance with 37 CPR. § 1.740(a)(l 1), a list of significant activities,
`
`BL 125377/0 during the applicable regulatory review period with respect of the approved
`
`undertaken by the Marketing Applicant, its predecessors, and affiliates, in BB-IND No. 9186 and
`
`product is provided at Exhibit 8.
`
`Merck Ex. 1135, Pg. 14
`
`

`

`Patent No.: 6,984,720
`
`- 12 -
`
`Docket No.: 029420.00155-USOI
`
`(1 2)
`
`A STATEMENT BEGINNING ON A NEW PAGE THAT IN THE
`
`OPINION OF THE APPLICANT THE PATENT IS ELIGIBLE FOR THE EXTENSION AND
`
`A STATEMENT AS TO THE LENGTH OF EXTENSION CLAIMED, INCLUDING HOW
`
`THE LENGTH OF EXTENSION WAS DETERMINED:
`
`(a)
`
`Statement of the eligibility of the patent for extension under 35 U.S.C.
`
`for extension is submitted by the owner of record of the patent or its agent in accordance with 35
`
`§156(e)(1).
`
`§156(a):
`
`Section 156(a) provides, in relevant part, that the term of a patent which claims a
`
`product, a method of using a product, or a method of manufacturing a product shall be extended
`
`if (i) the term of the patent has not expired before an application for extension is submitted; (ii)
`
`the term of the patent has never been extended under 35 U.S.C. §156(e)(l); (iii) the application
`
`U.S.C. §156(d); (iv) the product has been subject to a regulatory review period before its
`
`commercial marketing or use; and (v) the permission for the commercial marketing or use of the
`
`product after such regulatory review period is the first permitted commercial marketing or use of
`
`the product using the provision of law under which such regulatory review period occurred.
`
`As described below by corresponding number, each of these elements is satisfied
`
`(i)
`
`Pursuant to 35 U.S.C. §154, the term of United States Patent No.
`
`6,984,720 is currently set to expire on August 2, 2022. This Request is, therefore, being
`
`submitted prior to the expiration of the term of United States Patent No. 6,984,720.
`
`(ii)
`
`The term of this patent has never been extended under 35 U.S.C.
`
`Merck Ex. 1135, Pg. 15
`
`

`

`Patent No.: 6,984,720
`
`- l3 -
`
`Docket No.: 029420.00155-USOI
`
`(iii)
`
`This Request is being submitted by Medarex, the owner of record of
`
`United States Patent No. 6,984,720. '(See Exhibit 2). Medarex is the owner of record by virtue
`
`of the duly recorded assignment discussed above. This Request is submitted in accordance with
`
`35 U.S.C. §156(d) in that it is submitted within the sixty-day period beginning on March 25,
`
`2011, the date the product received permission for marketing under section 351 of the Public
`
`Health Service Act (PHSA) (42 U.S.C. §262), and ending on May 24, 2011. Moreover, this
`
`Request contains the information required under 35 U.S.C. §156(d).
`
`(iv)
`
`As evidenced by the March 25, 2011 letter from the FDA to EMS (Exhibit
`
`7), the product was subject to a regulatory review period under section 351 of the Public Health
`
`periods added together equal 3,878 days.
`
`Service Act (PHSA) (42 U.S.C. §262) before its commercial marketing or use.
`
`(v)
`
`The permission for the commercial marketing of the YERVOY
`
`(ipilimumab) Injection product is the first permitted commercial marketing and use of the
`
`product, as defined in 35 U.S.C. §156(t), under section 351 of the Public Health Service Act
`
`(PHSA) (42 U.S.C. §262). (See, e.g., Section (4), above.)
`
`(b)
`
`Statement as to length of extension claimed.
`
`The term of US. Patent No. 6,984,720, now expiring August 2, 2022, should be
`
`extended for 966 days, or to March 25, 2025, in accordance with 35 U.S.C. §156.
`
`As set forth in 35 U.S.C. §156(g)(l), the regulatory review period equals the
`
`length of time between the effective date of BB-IND No. 9186 of August 12, 2000, and the
`
`submission of the BL 125377/0 on June 25, 2010 (i.e., the “testing phase”), a period of 3,604
`
`days, plus the length of time between the submission of the BL 125377/0 on June 25, 2010 to
`
`BLA approval on March 25, 201 1 (i.e., the “approval phase”), a period of 274 days. These two
`
`Merck Ex. 1135, Pg. 16
`
`

`

`Patent No.: 6,984,720
`
`- 14 -
`
`Docket No.: 029420.00155-US01
`
`Pursuant to 37 C.F.R. § 1.775(d), the term of the patent as extended is determined
`
`by subtracting from the 3,878 day regulatory review period the following:
`
`(i) 1,977 days, which is the number of days in the IND and BLA periods on or
`
`before the issuance of US. Patent No. 6,984,720 on January 10, 2006; and
`
`(ii) 813 days, which is one-half the number of days remaining in the IND period
`
`after the subtraction of 1,977 days above (wherein half days are ignored for purposes of this
`
`subtraction, as provided by 37 C.F.R. § l.775(d)(1)(iii)).
`
`From the foregoing calculation, an extension of 1,087 days results, i.e., the
`
`remaining period under 35 U.S.C. §156(g)(1)(B)(i) (813 days) plus the remaining period under
`
`35 U.S.C. §156(g)(l)(B)(ii) (274 days). This length of an extension would provide a new
`
`expiration date for US. Patent No. 6,984,720 of July 24, 2025. However, this extension period
`
`is subject to two further potential limitations under 35 U.S.C. §156. One of these potential
`
`August 2, 2022 to March 25, 2025 amounts to 966 days.
`
`limitations does further limit the term of the patent and the other does not.
`First, under 35 U.S.C. §156(g)(6)(A), a maximum extension of five years is
`
`permitted (i.e., 1826 days in this case). Since the current expiry date of US. Patent No.
`
`6,984,720 is August 2, 2022, no patent term extension could extend the term of the patent
`
`beyond August 2, 2027. Consequently, this provision does not operate to limit the possible
`
`extension available to US. Patent 6,984,720.
`
`Second, under 35 U.S.C. §156(c)(3), the calculated extension period cannot lead
`
`to a patent term that wouldresult in a patent term exceeding 14 years after the date of approval,
`
`that is, a patent term expiring after March 25, 2025.
`
`In this case, 35 U.S.C. §156(c)(3) does
`
`operate to limit the possible extension available to US. Patent 6,984,720. The period from
`
`Merck Ex. 1135, Pg. 17
`
`

`

`(13) A STATEMENT THAT APPLICANT ACKNOWLEDGES A DUTY TO
`
`DISCLOSE TO THE COMMISSIONER OF PATENTS AND TRADEMARKS AND THE
`
`SECRETARY OF HEALTH AND HUMAN SERVICES ANY INFORMATION WHICH IS
`
`MATERIAL TO THE DETERMINATION OF ENTITLEMENT TO THE EXTENSION
`
`SOUGHT (SEE 37 C.F.R. §1.765).
`
`Applicant acknowledges a duty to disclose to the Commissioner of Patents and
`
`Trademarks and the Secretary of Health and Human Services any information which is material
`
`to the determination of entitlement to the extension sought.
`
`In accordance with the duty of disclosure described in 37 C.F.R. § 1.765 and
`
`acknowledged under 37 C.F.R. § 1.740(13), Applicant wishes to inform the Office that two
`
`review period for YERVOYTM (ipilimumab) Injection. Such patent term extension applications
`
`are with respect to US. Patent No. 6,984,720 (i.e., the present application) and US. Patent No.
`
`7,605,238,
`
`It is requested that the Office examine these extension applications concurrently so
`
`that a meaningful election can be made upon the receipt of a Notice of Final Determination and
`
`Requirement of Election as to which patent to ultimately extend in accordance with 37 C.F.R. §
`
`Patent No.: 6,984,720
`
`- 15 -
`
`Docket No.: 029420.00155-USOI
`
`Accordingly, United States Patent No. 6,984,720 is eligible for a patent term
`
`extension of 966 days.
`
`1.785.
`
`patent term extension applications have been filed concurrently with respect to the regulatory
`
`Merck Ex. 1135, Pg. 18
`
`

`

`Patent No.: 6,984,720
`
`- l6 -
`
`Docket No.: 029420.00155-USOI
`
`(14)
`
`THE PRESCRIBED FEE FOR RECEIVING AND ACTING UPON THE
`
`APPLICATION FOR EXTENSION (SEE 37 C.F.R. §1.20(i)):
`
`Please charge our Deposit Account No. 50-0740 in the amount of $1,120.00 to
`
`cover the fee for a request for extension of patent term. The Director is hereby authorized to
`
`charge our Deposit Account No. 50-0740, under Docket No. 02942000155, for any deficiency in
`
`the fees filed, asserted to be filed or which should have been filed herewith (or with any paper
`
`hereafter filed in this application by this firm), to prevent this application from being
`
`inadvertently abandoned. A duplicate of this Request (without Exhibits 1-8) is attached.
`
`Facsimile No.: (202) 662-6291
`
`1201 Pennsylvania Avenue, NW.
`Washington, DC 20004—2401
`Telephone No.: (202) 662-6000
`
`(15).
`
`THE NAME, ADDRESS, AND TELEPHONE NUMBER OF THE
`
`PERSON TO WHOM INQUIRIES AND CORRESPONDENCE RELATING TO THE
`
`APPLICATION FOR PATENT TERM EXTENSION ARE TO BE DIRECTED:
`
`Natalie M. Derzko
`COVINGTON & BURLING LLP
`
`Merck Ex. 1135, Pg. 19
`
`

`

`submission of three copies.
`
`Dated: May 16, 2011
`
`Respectfully submitted,
`
`Paul J. Berman
`
`Registration No.: 36,744
`COVlNGTON & BURLING LLP
`
`Patent No.: 6,984,720
`
`- 17 -
`
`Docket No.2 029420.00155-USOI
`
`Pursuant to 37 C.F.R. §1.740(b), this Request for Extension of Patent Term Under
`
`35 U.S.C. §156, including Exhibits 1-8, is accompanied by two additional copies, for a total
`
`1201 Pennsylvania Avenue, NW.
`Washington, DC 20004-2401
`(202) 662-6000
`
`Attorneys for Applicant
`
`Merck Ex. 1135, Pg. 20
`
`

`

`gm
`||||||||ll||l|llllllll|||||||||ll|l||||l||lllll|l|||lllllllllllllllllllllll
`USOO6984720B1
`
`laii/fl:
`
`(12) United States Patent
`Korman et al.
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 6,984,720 B1
`Jan. 10, 2006
`
`(54) HUMAN CTLA-4 ANTIBODIES
`
`(75)
`
`Inventors: Alan J. Korman, Piedmont, CA (US);
`Edward L. Halk, Sunnyvale, CA (US);
`Nils Lonberg, Woodside, CA (US);
`Yashwant M. Deo, Annandale, NJ
`(US); Tibor P. Keler, Otlsville, PA
`(US)
`
`Medarex, Inc., Annandale, NJ (US)
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 708 days.
`
`Appl. No; 09/644,668
`
`Filed:
`
`Aug. 24, 2000
`
`Related US. Application Data
`Provisional application No. 60/150,452, filed on Aug. 24,
`1999.
`
`Int. Cl.
`C1 2P 21/08
`C07K 16/00
`C07K 16/28
`
`(2006.01)
`(2006.01)
`(2006.01)
`
`US. Cl.
`
`............................ ,. 530388.22; 530/387.1;
`530/3879; 530/3881
`Field of Classification Search ............ .. 530/387.1,
`530/387.9, 388.1, 388.22, 388.15, 388.2,
`530/3887, 388.73, 388.75, 387.3
`See application file for complete search history.
`
`References Cited
`
`4,399,216
`4,681,581
`4,683,195
`4,683,202
`4,735,210
`4,740,461
`4,816,397
`4,921,040
`4,959,455
`5,101,827
`5,151,510
`5,194,594
`5,434,131
`5,530,101
`5,545,806
`5,545,807
`5,569,825
`5,585,089
`5,591,669
`5,612,205
`5,625,126
`121335500
`5,633,425
`5,643,763
`5,648,471
`5,661,016
`5,693,761
`5,693,792
`5,697,902
`
`>>>>>>>m>>>>>>>>>>>>>>>>>>>>>
`
`
`
`U.S. PATENT DOCUMENTS
`Axel et al.
`Coates
`Mullis et al.
`Mullis
`Goldenberg
`Kaufman
`Boss ct al.
`Ueruenduel ct al.
`Clark et al.
`Goldenberg
`Stec et al.
`Khawli et al.
`Linsley et al.
`Queen et al.
`Lonberg et al.
`Surani et al.
`Donberg et al.
`Queen et al.
`Krimpenfon et al.
`Kay et al.
`[nuberg et al,
`Rhodes
`Lonberg et al.
`Dunn et al.
`Buttram et al.
`Lonberg et a],
`Queen et al.
`Torii et al.
`Goldenberg
`
`5,703,057
`5,714,350
`5,721,367
`5,733,743
`5,741,957
`5,750,172
`5,756,687
`5,770,197
`5,770,429
`5,773,253
`5,777,085
`5,789,215
`5,789,650
`5,811,097
`5,814,318
`5,827,690
`5,844,095
`5,855,887
`5,874,299
`5,877,397
`5,885,796
`5,916,771
`5,939,598
`5,968,510
`5,977,318
`6,051,227
`6,075,181
`6,114,598
`6,150,584
`6,162,963
`6,207,156 131
`6,255,458 131
`6,682,736 131 *
`2002/0086014 A1
`
`>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
`
`12’] 997
`2’1 998
`2/1 998
`3/1 998
`4/1998
`5/1998
`5/1998
`6/1998
`6/1998
`6/1998
`7/1998
`8/1998
`8/1998
`9/1998
`9/1 998
`10/1998
`1 2/1998
`1/1999
`711 999
`3/1 999
`3/1 999
`6/1999
`8/1999
`1 0/1 999
`1 1/1999
`4/2000
`6/2000
`9/2000
`1 1/2000
`1 2/2000
`3/2001
`7/2001
`I [2004
`712002
`
`Johnston et al.
`Co et al.
`Kay et :1].
`Johnson et al.
`Deboer et al.
`Meade et al.
`Denman et al.
`Linsley et al.
`Lonberg et al.
`Linsley et al.
`Co et al.
`Berns et al.
`Lonberg et al.
`Allison et al.
`Lonberg et al.
`Meade et al.
`Linsley et al.
`Allison et al.
`Lonberg el al.
`Lonberg et al.
`Linsley et al.
`Hori et al.
`Kucherlapali el al.
`Linsley et al.
`Linsley et al.
`Allison et al.
`Kucherlapati et aI.
`Kucherlapali et a1.
`Kucherlapati et al.
`Kucherlapati et al.
`Kuchroo et al.
`Lonberg et al.
`Hanson et al.
`Korman et al.
`
`FOREIGN PATENT DOCUMENTS
`
`2205680 Bl
`0 E6 055 El
`0 323 997 El
`0 338 841 Bl
`0 216 846 B2
`0 463 151 Bl
`0 546 073 Bl
`WO 90/04036
`WO91/10741
`
`‘
`
`11/1998
`8/1991
`4/1993
`3/1995
`4/1995
`6/1996
`9/1997
`4/1990
`7/1991
`
`(Continued)
`
`OTHER PUBLICATIONS
`
`424/1441
`
`L. Green et al.: “Regulation of I3 Cell Development by
`Variable Gene Complexity in Mice Reconstituted with
`Human lmmunoglobulin Yeast Artificial Chromosome,” J.
`Exp. Med., vol. 188, No. 3, Aug. 3, 1998 483—495.
`
`(Continued)
`
`Primary Examiner—Phillip Gambel
`Assistant Examiner—Ilia Ouspenski
`(74) Attorney, Agent, or Firm—Darby & Darby
`
`(57)
`
`ABSTRACT
`
`The present invention provides human sequence antibodies
`against CI'IA-4 and methods of treating human diseases,
`infections and other conditions using these antibodies.
`
`14 Claims, 20 Drawing Sheets
`
`8/1983
`7/1987
`7/1987
`7/1987
`4/1988
`4/1988
`3/1989
`5/1990
`9/1990
`4/1992
`9/1992
`3/1993
`7/1995
`6/1996
`8/ 1996
`8/1996
`10/1996
`12/1996
`1/1997
`3/1997
`4/ 1997
`S/1997
`5/1997
`7/1997
`7/ 1997
`8/1997
`12/1997
`12/1997
`12/1997
`
`Merck Ex. 1135, Pg. 21
`
`

`

`US 6,984,720 B1
`Page 2
`
`FOREIGN PATENT DOCUMENTS
`W09203918
`3/1992
`W09222645
`12/1992
`W0 92/2647 A1
`12/1992
`12/1992
`WO 92/22670 A1
`W0 93/(D431 A1
`1/1993
`6/1993
`WO93/12227
`WO94/02602
`2/1994
`11/1994
`WO94/75585
`W0 94/29444
`12/1994
`WO 95/01994
`1/1995
`WO 95/03408
`2/1995
`WO 95/24217
`9/1995
`W095/33770
`12/1995
`WO 96/14436
`5/1996
`7/1996
`WO 96/22380
`WO96/33735
`10/1996
`W096/34096
`10/1996
`W097/07671
`3/1997
`W0 97/13852
`4/1997
`WO 97/20574
`6/1997
`WO 97/38137
`10/1997
`6/1998
`WO98/24884
`W098/24893
`6/1998
`W098/24893
`6/1998
`9/1998
`W098/37757
`WO98/42752
`10/1998
`WO 98/46996
`10/1998
`11/1998
`WO 98/50433
`1/2000
`WO 00/00569
`WOOO/10383
`3/2000
`WO 00/32231
`6/20