Application for Extension of Patent Term and Exhibits

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t , . S@l I of DOCKET NO,: \ APPLICANT(S): 0 TRADEMARK OFFICE STAMP HEREON A&KNOWLEDGES RECEIPT OF THE FOLLOWING PARERS: MONT UCTENSION OF TIME ( TRANSMITXAL LETTER MISSING PARTS RESPONSE WITH. RECL AMENDMENT a SUPPLEMENTAL J-J PREUMINARY REPLY TO OFFICE ACTION RESTRIC710N/ELECTION REPLY q WtTH DISK SEQUENCE LISTING CPA REQUEST TRANSM1TTAL NOTICE OF APPEAL APPEAL BRIEF (TRIPLICATE) q a a q q q q q q a a MAXOrj MSCLOSURE f-J FORM 1449 & PRIORITY DOCUMENT(S) NO. DECLARATION UNPER 8 LE-T-I-ER DRAFTSMAN TO SliEffS OF RRAWtNGS f3 ISSUE FEE TRANSMl.lXAL FORM IN THE UN4TED STATES PATENT AND TRADEMARK In Re Application of: Vet-mud REDDY et al Dffiie OFFtCE of the Deputy Assistant a?$ Qb@ Commissioner for Patent Fotciy Patent No.: 4,840,896 Issued: June 20,1989 For: HETEROPOLYMERIC PROTEIN : Atty.% Docket: REDDY=BEXT Date: November 20,200tl THE COMMISSIONER OF PATENTS Washington, D.C. 20231 Sir: Transmitted [ [ m ] ] herewith is Apolication application. Applicant(s) AND TRADEMARKS %%ZCElVE for Extension of Patent Term and Exhibi claim small entity status. See 37 C.F.R. §1,27. in the above-identified Small Entity Status: No additional fee is required. The fee has been calculated as shown below: OR ADDITICINAL FEE -rOTAt. If the entry in Cal. 1 is less than the entry in Cot. 2, write “0’ in Col. 3. If the “Highest Number Previously Paid for” IN THIS SPACE is Jess than 20, write “20’ in this gaca. If the “Highest Number Previously Paid for” IN THIS SPACE is less than 3, write “3” in this space. The “Highest Number Previously Paid For” (total or independent) number of claims originally filed. Conditional Petition for Extension of Time requests that this be considered with 37 CFR 1.136(a}. $ gR TOTAL 1 $ I is the highest number found from t&e equivalent box in bol. 1 of a prior amendment of the if any extension of time for a response is required, applicant It is hereby petitioned for an extension of time in accordance Small Enthy Response r I Filed Within First Second Third Fourth $ 55.00 $ 196.00 $445.00 $635.00 a petition therefor. fee required by 37 CFR 1 .I7 is catculated as shown below: The appropriate Other Than Small Entity Response Filed Within I r f I 1 I First Second Third Faurth f 0 $ 110.00 890.00 Set $ 390.00 $139O*M) I 1 I 1 I 1 [ ] Month After Time Period Set Less fees ($ ) alreadypaid for _ month(s) extension of time on I I Month After Time,Period Fee under 37 C.F.R. $Y.20@(1) for receiving and acting upon application Please charge my Deposit Account No. 02-4036 in the amount of $ Credit Card Payment Form, PTO-2038, is attached, authorizing for extension: %t.l20.00 payment in the amount of $1.120.01) which may be required ia o&rneotion,with this application or credit any limited to paymentof alJfeesaseootated~with thiscommunication, including intended to indude alt fees fog the presentation of extra claims under 37 CFR of the case. Thfs blanket authorization does f& tncfude patent issue fees The Commissioner is hereby autho&ed and requested to charge any additional fees overpayment to Deposit Account No. 02-4036. This authorization and request is not any Extension of Time fee, not covered by check or specific authorization, but is also $1 .I6 and all patent processing fees under 37 CFR §Y .17 throughout the prosecution under 37 CFR Bl.18. t3ROWDY AND NEtMARK Facsimile: Telephone: (202) 737-3526 (202) 628-5197 . PTO-2038 (02-2000) Approved fbruse tlmagh W3fI2003. OMB 0651-0043 Uidted StatdsPatentamI Trademark Mice; U.s; DEPARTMENT OF COMMERCE Undq the Paperwork Reduction Act of 1995,no personsare required to respmd to a collection oftiomation unless it displays a valid OMB control number. 1: Credit %ard Payment Form Credit Card Account #: 3727-X26626-01094 08/03 Roger Credit Card Expiration Date: Neme as it Appears on Credit Card: Payment Amount $(US Dollars): f,. Browdy requasted, and will not not& the payar of such’ amaunts (37 CFR 1.26). Retind of a fee p&d by credit card v&f be.via @edit to the credit card account, Service Charge: There is a 50.00 service charge for procassfng each payment refused (inc&d&t a check returned “unpaid”) or charged ----- .~ Street Address 1: Street Address 2: Xy: State: country: daytime Phone #k 624 Ninth Street, NW Washirigton DC USA 202-628-5197 f Faxi+~‘ -202~737-3528 Other ,Fee DON Customer No. re United States Pate& & Tradenrark Offie willnot be iiabIe in the eve@t&at t&s creditclvdnumbler becwtqpElblic knowledge. IN THE UNITED STATES E'ATEWX'AND BEG OFFICE In re Application RJ&DY et al Patent-No.: Issued: For: of: 1 ,' Office of the Deputy Assistant Commissioner for Patent 'Policy and Projects Washington, D.C. 4,840,896 June 20, 1989 ; 1 J ) November 20, 2000 Atty.Docket: REDDY==2EXT HETEROPOLYMERIC PROTEIN APPLICATION i?OR EXTENSICTN OF PATENT TERM Honorable Commissioner for Washington, D.C. 20.231 Sir: In accordance Corporation, extension through with Patents 35 USC 156, patentee, attorney, Genzyme for the undersigned hereby applies patent. -Following of the term of the above-identified required by 37 C.F.R. product,is is the information (a) (1) 51.740. chorlogonadotropin gonadotropin glycoprotein - designated cx (r- The approved alfa hCG). also known.as. recombinant alfa human chorionic Choriogonadotropin is a wate‘ soluble r linked subunits consisting of two non-covalently and j'3 - consisting respectively, Asn-'78 Ser-132 with of 92 and 145 amino acid carbohydrate moieties residues, to Asn-52 and Se.+121, Ser-127; linked (on the CY. subunit) and Ser-138 and Asn-23, Asn-30, (on the p subunit), The full. amino acid In re of Patent ru3. 4,840,896 sequences as follows: (x subunit: of the 01 and p subunits of choriogonadotropin alfa are 10 Ala Pro Asp Val Gln Asp Cys Pro Glu Cys 30 Pro Gly Ala Pro Ile Leu Gin Cys Met Gly 50 Leu Arg Ser Lys Lys Thr Met Leu Val Gln 70 Val Ala Ala Lys Ser Cys Tyr Sex Asn Arg VaZ Thr Tyr Val 90 Cys His His Met Lys Gly 92 Ser Gly Phe Lys Val Glu Asn His Lys Asn Val Ths Ser Glu Ser Thr Cys Cys Cys Phe Ser Arg Ala Tyr Pro Thr Thr 'Leu Gla Glu Asn Pro Phe Phe Ser 20 Gln 40 Pro 60 Cys 80 Thr Thr Cys Tyr B-subunit 10 20 Pro Ile Asn Ala Thr Leu Ala Val Glu Lys 40 Thr Thr Ile.Cys, Ala Gly Tyr Cys Pro Thr 60 Ala Leu Pro Gin Va$ Val Cys Asn,,Tyr Arg 80 Gly Cys Pro Arg Gly Val Am Pro Val Val 100 Leu Cy5 Arg $rg Ser Thr Thr Asp Cys 120 Asp Pro Arg Phe GLn Asp Ser SeL- Ser 140 Pro Ser Axg I+u Pro Gly Pro Sex Asp Thr Ser Lys Glu Pro Leu Arg Pro Arg Cys Axg 30 Glu Gly Cys Pro Val Cys Ile Thr Val Asn 50 Met Thr Arg Val Leu Gln Gly Val Leu Pro 70 Asp Val Arg Phe Glu Ser Ile Arg Leu Pro 90 Ser Tyr Ala Val Ala Leu Ser Cys Gin Cys Ala 110 Gly Gly Pro Lys Asp His Pro Leu Thr Cys Asp 130 Ser .. Pro Lys Ala Pro Pro 145 Pro Ser lieu Pro Ser Ile Leu Pro Gln O-glycosylation site Asn: N-glycosylation (a) (2) site Ser: The pro‘ duct Food, Drug was approved Act under Section 505(b) of the Federal and Cosmetic -2- (21 USC 355(b)). In re of Patentk . 4,840,s;; fa) (3) commercial marketing The product received Section permission 505(b) fbr of the Federal or u&e under Food, Drug and Cosmetic (a) (4) product Federal Act), Act on September product 20, 200.0. is a human biological terms are used in the Health Service As the present and not a drug product Food, Drug and Cosmetic 37 C.F.R. W (5) §1.740fa) (as those Act and the Public (4) is not applicable, application for that is being submission submitted pursuant be to The present day period It within the sixty permittbd 37 C.F.R. filed letter §1.72O(f). sixty is required the application ,within days following the date of the FDA approval day period is expires on of September 20, ZQOO. The sixty As November 19, 2000, could November 19, 2000, date on which a Sunday, the last the application be filed is November 20, 2000 (37 C.F.R. §i1.7(a)). Ia) (6) The patent 4,840,896 for which an extension the inventors is being are sought Vermuri is U.S. patent of which B. Reddy, Nancy Hsiung, The date of issue Anton K. Beck, and Edward G. of Bernstine. expiration was June 20, 19'89,, and the.date is June 20, 2006,. (a) (7) A copy of patent the entire 4,840,896 specification &s attached (including hereto as Exhibit claims A, including and drawings). -3- In re of Patent LUO. 4,840,896 (a) (8) Attached hereto as Exhibit with 3 is‘ a respect copy of the to this of Certificate patent. receipts Also of Correction attached which hereto has issued as Exhibits C and D are copies that of maintenance fee payments establishing paid with the first to this and second maintenance patent. (4 (9) fees were timely respect Th.e patent Attached claims hereto a me2;hod‘ manufacturing of as Exhibit E is a copy of from the process. Exhibit the approved a portion original E includes manufacturing manufacturing scope of claim Exhibit July product. of Section NDA submitted C, "Method of~Manufacture", during the FDA approval pages numbered 032-049. process process of 'the approved of the approved These documents product, product This falls show the within hereto the as 17 of the '896 patent, Also attached F are sections 26, 2000, Exhibit showing relating l-3.2 of a submission to the FDA dated for the drug The this product. claim to bioassay specification product. following reads Patent F includes pages numbered 002-014. manner in which the approved Approved Product demonstrates.the on the method of manufacturing Claims 1. A method for producing biologically active hCG comprising See Figure CM&-5 on page 049 of Exhibit E. It shows that the final product of the purification process of the culture medium ~from the bioreactor is "r-hCG DRUG SU%STAHCE". Exhibit F shows the biological activity of the r-hCG In re of Patent ,.a. 4,840,896 drug product, Note the last paragraph on page 004 which shows that the. mean specific activity was 26,400 IU per mg rhCG . Thus, as the hCG can be measured in international units, biologically active hCG is produced by the method. culturing host mammalian cells See pages 046 and 047 of Exhibit E which indicates that the r-hCG is produced from CHO cells. See also page 034 in the section "Mode of introduction into the production s@ain" which indicates that the production strain is a CHO cell line. CHO is Chinese hamster ovary cells. Hamster cells are mammalian cells. af The section at the bottom of page 034 of Exhibit E, entitled into the "M0de of introduction production strain", states that cells were c&transfected with uncut pHcxDHFR containing the cx hCG and pHLHPODC containing the P-hCG gene, The construction of the cx hCG gene,expression vector is discussed at pages 032 and 033. Accordingly, it is clear that the (x and p subunits are introduced in separate vectors. Thus, the inammalian cells comprise a. first expression vector encoding the cx subunit of hCG. ' The construct.icm of the @ hCG gemi expression vector is discussed on pages 033 alid 034 o‘ Exhibit f E. As discussed above, the pa,ragraph at the bottom of page 34 indicates that the a and fi gene vectors are introduced separately. Thus, the mammalian cells also -5- comprising a first expression vector encoding the cx subunit said hCG and a second encoding hCG. expression vector the p subunit of said In re of Patent HO. 4,840,896 comprise a second expression vector encoding the p subunit hCG. (4 (10) (i) New Drug IND number submitted 149. (IND) The effective ddte 2, of the Investigational and was assigned of application was October 1995, 48934. The New Drug Application 23, 1999, was initially NDA,number 21- on November and was assigned 20, 2000. The NDA was approved ia) (11) on September is The following undertaken review period: a brief description of significant during the activities applicable by the marketing applicant IND submitted IND received by FDA September October October November February April 2, IO; 29, 1995 1995 1994 1995 1996 FDA Action Letter and Acknowledgement of Receipt Study Approval 7927 submitted for to IND 28, 1, 7927 to commence Date 7927 Completion NDA submitted NDA received FDA letter 1998 23, 24, 30, 23, 1999 1999 1999 2000 November November acknowledging receipt November February March USAN name adopted Correction to USAN information 2.2, .2000 Submission of 120-day safety report and additional clinical and bioequivalents reports -6- April 7, 2000 In re of Patent NO. 4,840,896 Submission of information package CMC for diluent Submission financial of additional disclosure information for the drug June 16, June 28, 2000 2000; July 5,,2OOO Bioassay specification drug substance and the product Withdrawal mcg doses Withdrawal manufactured of of July August 26, 1, 2000 2000 500 mcg and 250 alternate diluent by Pharma Hameln for August August 7, 2000 29, 2UaOO 6, 2000 20, 2000. patent Applicant will extend was periods the August 3, 2000 Response to CMC request information Addition for drug Withdrawal packaging NDA approval (a) 4,840,896 claims patent is of microplasma testing substance release of alternate facility September September (12) Applicant for..patent extension 2009, using is of term the opinion.that eligible of extension. a length through of 1054 days which May 9, The length the rS1.775: following of extension dates determined as set (c) (1) (cl (c) (2) as follows in and time forth 37 C.F.R. lo/IO/1995 11/24/1999 through through 11/24/1999 09/20/2000 1506 301 1807 (c) (I)+ Ic) (2) -7- In re of Patent DO. 4,840,896 td) (1) (il none not known f (cl (U-(d) (c)-(d((l)(i)-(d) 06/20/2006 09/20/2000 earliest 06/20/2006 earliest W (5) 0-i) (a) (13) 0 0 (I) (i) )42 (l)(ii)-(d) f Id) (1) (1) (iii) 753 1054 05/09/2009 09/20/2014 05,'09/2009 06/20/2011 05/09/2009 05/09/2009 acknowledges and Trademarks or the Secretary a duty to disclose to of any Cd) (1) (ii) (d) (1) (iii) (d) (1) Cd) (2) (d) (3) + 14 years .' (d.1 (4) Cd) (5) (i) (d) (5) C4 tdl of fd) (2) and Cd) (3) + 5 years ' and W (5) 0-1 of (d)(4) Applicant of Patents the Commissioner Health and the Secretary of Agriculture and Human Services which information is material. sought. Attached to the determination of entitlement to the extension (a) (14) hereto payment is PTO Form 20-38, Credit in the amount af $1,120.00 for receiving Card in Payment Form, authorizing accordance with 37 C.F.R, for $$1.2O(j)(I) extension. and acting upon the application (4 (15) person present The name, address and telephone relating number of the to the to whom inquiries application and correspondence are to be directed is as follows -8- In re of Patent iuo', 4,840,896 Roger L. Browdy BROWDYAND NEIMARK, P.L.L.C. 624 Ninth Street, N.W. Suite 300 Washington, D.C. 20001~-5303 Telephone: Facsimile: (a) is a duplicate (16) 202-628-5197 202-737-3528. certifies application Roger attorney Office owner relating the that attached papers. hereby to general 4,840,896 hereto The undersigned all I, that the of the the present of Ia) 117) declare practice authority to act and state before from on their undersigned L.,Browdy, authorized I am a patent Patent and Trademark the matters and have of patent Genzyme Corporation, behalf in patent to patent contents to to of the 4‘ 840,896. foregoing §1.740. pursuant claimed, the I have application I believe to §1.710. to reviewed being that the and understand submitted patent that is pursuant subject 3'7 C.F.R. extension of the length by I believe any reduction an extension caused subject by a determination under with 35 USC Secretary (2)(B) of Health that and Human Services did not act 156(d) justified believe meets forth applicant due diligence, regulations. is of being a patent is I sought as set i under that the in the 35 USC 156 and the patent for §1.720. for which applicable the of extension the term conditions 37 C.F.R. extension -9- In re of Patent ~0. 4,840,896 I declare own knowledge information these are further true that all all statements statements to be true; knowledge made herein made on and further that willful or the of my and that and belief are believed the that false statements were made with like statements imprisonment, United jeopardize and the so made are punishable under Section such willful the patent. Respectfully by fine or both, 1001 o:f Title false 18 of States the Code and that validity of statements may submitted, P.L.L.C. Owner BROWDY AND NEIH&RK, Attorneys for-Patent Registration RLB:al:rd 624 Ninth Washington Telephone Facsimile Street, N.W, D.C. 20001-5303 No.: (202) 628-5197 No.: (202) 737-3528 No. 25,616 F:\,S\S,erl\Reddy2Ext\PatentTermExt.doc - 10 -

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