Docket No.: CGR5001USCNT1
`
`I hereby certify that this correspondence is being transmitted Via The Office
`
`Electronic Filing System (EFS) in accordance with 37 CFR l.6(a)(4).
`
`Date of Electronic (EFS) Transmission:
`
`June 4, 2013
`
`Signature: /Laurie A. Phillips/ Name: Laurie A. Phillips
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`‘
`
`Cancer
`
`Z
`
`In re Application of:
`
`:Ar>r31i<i:7oinit”(si)i3i
`Application No.:
`
`13/034,340
`
`i Title:
`
`Mail Stop Amendment
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Dear Sir:
`
`RESPONSE
`
`In response to the final Office Action mailed March 4, 2013, Applicant submits
`
`the following amendments and remarks.
`
`A list of the Claims are reflected in the listing of claims, which begins on page 2
`
`of this paper.
`
`Remarks/Arguments begin on page 4 of this paper.
`
`Page 1 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 1
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`Listing of Claims:
`
`1-36. (Canceled).
`
`37. (Previously presented) A method for the treatment of a prostate cancer in a human
`
`comprising administering to said human a therapeutically effective amount of abiraterone
`
`acetate or a pharrnaceutically acceptable salt thereof and a therapeutically effective
`
`amount of prednisone.
`
`38. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is from
`
`about 50 mg/day to about 2000 mg/day.
`
`39. (Previously presented) The method of claim 38, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is from
`
`about 500 mg/day to about 1500 mg/day.
`
`40. (Previously presented) The method of claim 39, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is about
`
`1000 mg/day.
`
`Page 2 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 2
`
`

`
`Docket No.: CGR500 lUSCNT1
`
`41. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the abiraterone acetate or a pharrnaeeutically acceptable salt thereof is
`
`administered in at least one dosage for1n comprising about 250 mg of abiraterone acetate
`
`or a pharrnaceutically acceptable salt thereof.
`
`42. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the prednisone is from about 0.01 mg/day to about 500 mg/day.
`
`43. (Previously presented) The method of claim 42, wherein the therapeutically effective
`
`amount of the prednisone is from about 10 mg/day to about 250 mg/day.
`
`44. (Previously presented) The method of claim 44, wherein the therapeutically effective
`
`amount of the prednisone is about 10 mg/day.
`
`45. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the prednisone is administered in at least one dosage form comprising about 5
`
`mg of prednisone.
`
`46. (Previously presented) The method of claim 37, comprising administering to said
`
`human about 500 mg/day to about 1500 mg/day of abiraterone acetate or a
`
`pharrnaceutically acceptable salt thereof and about 0.01 mg/day to about 500 mg/day of
`
`prednisone.
`
`Page 3 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 3
`
`

`
`Docket No.: CGR500 lUSCNT1
`
`47. (Previously presented) The method of claim 46, comprising administering to said
`
`human about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`48. (Previously presented) The method of claim 37, wherein said prostate cancer is
`
`refractory prostate cancer.
`
`49.
`
`(Previously presented) The method of claim 48, wherein the refractory prostate
`
`cancer is not responding to at least one anti-cancer agent.
`
`50. (Previously presented) The method of claim 49, wherein the at least one anti-cancer
`
`agent comprises a hormonal ablation agent, an anti-androgen agent, or an anti-neoplastic
`
`agent.
`
`51. (Previously presented) The method of claim 50, wherein the hormonal ablation agent
`
`comprises deslorelin, leuprolide, goserelin, or triptorelin.
`
`52. (Previously presented) The method of claim 50, wherein the anti-androgen agent
`
`comprises biealutamide, flutamide, or nilutamide.
`
`53. (Previously presented) The method of claim 50, wherein the anti-neoplastic agent
`
`comprises docetaxel.
`
`Page 4 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 4
`
`

`
`Docket No.: CGR500 lUSCNT1
`
`54. (Previously presented) The method of claim 48, comprising administering to said
`
`human about 500 mg/day to about 1500 mg/day of abiraterone acetate or a
`
`pharrnaceutically acceptable salt thereof and about 0.01 mg/day to about 500 mg/day of
`
`prednisone.
`
`55. (Previously presented) The method of claim 54, comprising administering to said
`
`human about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`56. (Previously presented) The method of claim 53, comprising administering to said
`
`human about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`Page 5 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 5
`
`

`
`Docket No.: CGR5001USCNTl
`
`Remarks
`
`Claims 37-56 are pending.
`
`Re°ections Under 35 U.S.C.
`
`103
`
`The rejection of claims 37-56 under 35 USC §103(a) as allegedly being
`
`unpatentable over O’Donell er al.
`
`(British Journal of Cancer 90:2317-2325 (2004))
`
`(“O’Donell”), in view of Tannock et al. (Journal of Clinical Oncology I4:1756-1764
`
`(1996)) (Tannock”) was maintained. Applicant respectfully traverses this rejection.
`
`In Applicant’s previous reply, submitted January 11, 2013 (the “January Reply”),
`
`Applicant submitted the Ryan article. Ryan showed,
`
`inter alia,
`
`that the “median
`
`radiographic progression-free survival was 16.5 months with abiraterone-prednisone and
`
`8.3 months with prednisone alone .
`
`.
`
`. Radiographic progression-free survival was
`
`positively correlated with overall survival.” According to the Office,
`
`“the superior
`
`results of using abiraterone and prednisone together is expected because abiraterone and
`
`prednisone are known to be individually effective in treating prostate cancer. At least
`
`additive effective [sic]
`
`is expected.”
`
`However,
`
`the Office failed to provide any
`
`reasoning to support the expectation of at least an additive effect.
`
`In fact, the Off1ce’s
`
`own cited art is in opposition to the Off1ce’s statement that at least an additive effect is
`
`expected.
`
`Based on Tannock, the art cited by the Office, one of ordinary skill in the art
`
`would not expect at least an additive effect for overall survival of abiraterone and acetate
`
`and progesterone. Tannock teaches that “[t]here was no significant difference in overall
`
`survival
`
`[between prednisone
`
`alone
`
`and prednisone plus
`
`the
`
`anticancer
`
`agent
`
`mitoxantrone.]” One of ordinary skill in the art, reading Tannock, would expect there to
`
`be no difference in survival between one cancer agent alone, and that same cancer agent
`
`in combination with prednisone. Thus,
`
`the present invention possesses unexpected
`
`results and is non-obvious over the cited art.
`
`Further,
`
`the present
`
`invention has displayed commercial success. Applicant
`
`submits herewith the currently United States Food & Drug Administration approved label
`
`Page 6 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 6
`
`

`
`Docket No.: CGR5001USCNT1
`
`for ZYTIGATM (the “ZYTIGA label”). The ZYTIGA label indicates that “[abiraterone
`
`acetate] is a CYP17 inhibitor indicated in combination with prednisone for the treatment
`
`of patients with metastatic castration-resistant prostate cancer.” Taking ZYTIGA in
`
`accordance with the approved label represents a commercial embodiment of the presently
`
`claimed invention.
`
`Applicant also submits herewith a news release from the U.S. Food and Drug
`
`Administration dated December 10, 2012 and titled “FDA expands Zytiga’s use for late-
`
`stage prostate cancer.” As can be seen from this 2012 news release, ZYTIGA was
`
`initially approved in April 2011 for use in patients whose prostate cancer progressed after
`
`treatment with docetaxel, a chemotherapy drug. ZYTIGA was further approved in
`
`December 2012 for use in prostate cancer patients prior to receiving chemotherapy.
`
`Applicant also submits two further news releases from the U.S. Food and Drug
`
`Administration, one dated June 17, 2010, announcing approval of Jevtana for use in
`
`prostate cancer; and the other dated August 31, 2012, announcing the approval of Xtandi
`
`for use in patients whose prostate cancer progressed after treatment with docetaxel.
`
`Applicant also submits herewith “Pharmaceuticals Commericial Overview”, a
`
`slideshow presented by Joaquin Duato on May 23, 2013 and currently available at
`
`http ://f11es.shareho1der.com/downloads/J N J/25 14 1 73 625x0x666408/bb2972ea-2099-
`
`4ab4-b2a3 -afc3 9e7105 94/Pharrnaceutical_Commercial_Overview_JNJ2013.pdf
`
`(the
`
`“2013 slideshow”). According to the 2013 slideshow, at slide 11, ZYTIGA is the most
`
`successful oral oncology launch in history.
`
`The 2013 slideshow, at slide 12, further shows the July 2012 to April 2013
`
`ZYTIGA market share of chemo refractory prostate cancer patients, i.e., patients who
`
`have previously received chemotherapy treatment and the December 2012 to April 2013
`
`market share of chemo naive prostate cancer patients,
`
`i.e., patients who have not
`
`previously received chemotherapy treatment. As can be seen from the figure on the left
`
`of slide 12, ZYTIGA had almost 70% market share in July of 2012 for chemo refractory
`
`prostate cancer patients, just slightly over a year after ZYTIGA’s initial approval, and
`
`despite the fact that a JEVTANA had been approved two years earlier. Despite another
`
`product, XTANDI, being introduced in August of 2012, by April of 2013, ZYTIGA was
`
`Page 7 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 7
`
`

`
`Docket No.: CGR5001USCNT1
`
`still the market leader as of April 2013 with 57% market share in chemo refractory
`
`prostate cancer patients.
`
`As can be seen from the figure on the right of slide 12, shortly after its approval
`
`for chemo-naive patients in December 2012, ZYTIGA had a market share of 15%. As of
`
`April 2013, ZYTIGA’s market share was 20%, higher than two other available therapies,
`
`docetaxel and XTANDI, and approaching the market share of bicalutamide, a drug first
`
`approved in 2001 for prostate cancer.
`
`Thus, not only is ZYTIGA the most successful oral oncology launch in history,
`
`two years after its initial approval it is still the market leader for chemo refractory
`
`patients despite an earlier-introduced therapy and a later-introduced therapy. ZYTIGA
`
`also holds a strong market share in the chemo naive prostate cancer population, despite
`
`the presence of other marketed products. This commercial success demonstrates the non-
`
`obviousness of the presently claimed invention.
`
`Even assuming, arguendo, the cited art suggests the claimed combination, the
`
`present invention has shown surprising results, and commercial success. Thus, the claims
`
`are non-obvious over the cited art. Accordingly, Applicant requests reconsideration and
`
`withdrawal of the rejection under 35 USC §103(a).
`
`Page 8 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 8
`
`

`
`Docket No.: CGR500 lUSCNT1
`
`III. CONCLUSION
`
`Early consideration and prompt allowance of the claims are respectfully requested.
`
`Should the office require anything further,
`
`it
`
`is
`
`invited to contact Applicant’s
`
`representative at the telephone number below.
`
`Applicant respectfully requests that a timely Notice of Allowance be issued in the
`
`present application. Should the office require anything further, it is invited to contact
`
`Applicant’s representative at the telephone number below.
`
`JOHNSON & JOHNSON
`One Johnson & Johnson Plaza
`
`New Brunswick, NJ 08933-7003
`(732) 524-3957
`Dated: June 4, 2013
`Customer No.: 27777
`
`Respectfully submitted,
`
`/Andrea Jo Kamage/
`By:
`Andrea Jo Kamage
`Reg. No. 43,703
`
`Page 9 of 9
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 9
`
`

`
`I hereby certify that this correspondence is being transmitted Via The Office
`
`Electronic Filing System (EFS) in accordance with 37 CFR 1.6(a)(4).
`
`Date of Electronic (EFS) Transmission:
`
`June 4, 2013
`
`Signature: /Laurie A. Phillips/ Name: Laurie A. Phillips
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`Applieant(s):
`
`Alan H. Auerbaeh
`
`:: Conf. No.:
`
`1597
`
`
`
` 1"IIIII'MéifidifiEhdieéififiéiéitiéfiéidiirféétiiigCéhééfiiI
`
`““““““““““““““““““““““
`
`ES{a{iiiii{éf}""'
`
`San Ming R. Hui
`'
`
`p
`
`Mail Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`
`Alexandria, VA 22313 -1450
`
`NOTICE OF APPEAL
`
`Applicant hereby appeals to the Board of Patent Appeals and Interferences from the decision
`
`of the Examiner dated March 4, 2013 finally rejecting Claims 37-56 of the aboVe—identified
`
`application.
`
`The item(s) checked below are appropriate:
`
`1.
`
`2.
`
`P’
`
`IXIIZIEIIZIIZIElEl
`
`An extension of time to respond to the final rejection was granted on
`month(s).
`A Petition For Extension Of Time under 37 CFR 1.136 is attached hereto in
`
`for
`
`triplicate.
`A timely response to the final rejection has been filed.
`Fee $5 00.00: for filing of Notice of Appeal
`Not required (fee paid in prior appeal)
`Charge to Deposit Account No. 10-0750/AJK/CGR5001.
`The Commissioner is hereby authorized to charge any additional fees which may be
`required, or credit any overpayment in connection herewith to Deposit Account No.
`10-0750/AJK/CGR5001.
`
`Respectfully submitted,
`
`.1OHNSON & .1OHNSON
`One Johnson & Johnson Plaza
`
`New Brunswick, NJ 08933-7003
`(732) 524-3957
`Dated: June 4, 2013
`Customer No.: 27777
`
`/Andrea Jo Kamage/
`By:
`Andrea Io Kamage
`Reg. No. 43,703
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 10
`
`

`
`S/4,v’1 3
`
`Press Announcentznts > Ft?-A approves new treatment for a type of late stage i rcetzate cancer
`
` ,
`
`,
`
`
`.,
`
`\\\\
`
`FEA NEWS RELEASE
`
`For immediate Reiease: Aug. 31, 2012
`Media Enquiries: Erica Jefferson, 301—796~4£i88,
`tfionsurner Enquiries: 8E'ét'£~Ii\iFi’3—FDA
`
`
`
`n
`
`n
`to . h
`
`. cs ox:
`
`sea approves new treatment for a type of iate stage prostate cancer
`
`The US, Food and Drug Adrninistration today aizrpr-3-ved Xtandi ijenzaiutami-;ie) to treat men with iate—stage
`(metastatic) castration~resistant prostate cancer that has spread or recurred, even with medicai or surgicz
`therapy to minimize testosterone.
`
`Approved for prostate cancer patients nreviousiy treated with docetaxei, another anti~cancer treatment,
`Xtandi was reviewed under the FDA’s priority review program. The program provides fa‘ an expedited si:<~
`in;-nth review for drugs that may after major advances in treatment -or that provide a treatment when no
`adequate therapy exists. Xtandi received Fill-A approyai three months ahead of the product's prescrir,=tion
`drug user fee goai date of ixioy. 22, 2012,
`
`“The need for additienai treatment options for advanced prostate cancer continues to be important for
`patients,” said Richard Pazdur, it/i.[)., director of the Ciffice of riematoiogy and Oncoiogy Prc-ducts in FDA’s
`Center for Drug Evaiuation and Research. “Xtandi is the iatest treatment for this disease to demonstrate its
`abiiity to extend a patient’s iife.”
`
`Prostate cancer forms in a giand in the maie reproductive system found oeic-w the biadder and in front of
`the rectum. The male sex hormone testosterone stirnuiates the prostate tumors to grow. Accc-rding to the
`Natic-nai Cancer Institute, an estimated 241,74-O men wiii he diagnosed with pr-3-state cancer and 28,173 wii
`die from the disease in 2012.
`
`The safety and effect'iveness of Xtandi was evaiuated in a study of 1,199 rsatients with metastatic
`castration~resistant prostate cancer who had received prior treatment with d-ocetaxei. The study was
`designed to measure c-veraii surviyai (the iength of time hefore death) in men receiving Xtandi compared
`with men receiving a piaceho {sugar piii). The median c-veraii survivai for patients receiving Xtandi was 18.4
`months, compared with 13.6 months for the patients who received piaceho.
`
`The most common side effects observed in study participarnzs taking Xtandi were weakness or fatigue, haci
`pain, diarrhea, joint pain, hot ‘flush, tissue sweiiéng, rnuscuiosi<.eie'tai pain, headache, upper respiratory
`infections, dizziness, spinai cord compression and cauda equina syndn:-me, nwuscuiar weakness, difficuity
`sieeping, ic-wer i“espiraton,/ infections, hiood in urine, tingiing sensation, anxiety, and high biood pressure.
`
`Seizures occurred in appro><irnateiy 1 percent of those receiving Xtandi. Patients in the study who had a
`seizure stiopped ><tandi therapy. The ciinicai study exciuded patients with a history of seizure, an urideriying
`brain injury with ioss of consciousness, a temporary
`in biood to the hrain within the past 12
`months, a stroke, hrain metastases, an ahnorrnai connection of the arteries and veins in the brain, or
`patients tai<ing n”:edications ‘that
`tower the seizure threshold. The safety of Xtandi is 1.ii“ii«<i“it)Wii
`in
`patients with these conditions.
`
`Xtandi wiii be co— rnari<eted by Asiieiias Pharrna U.S., Inc. of Nortihhrook, ‘it. and iviedivation, inc. of San
`Francisco, CA.
`
`For rrpre information:
`
`
`
`FDA, an agency within the U.S. Department of Heaith and i-iurnan Services, protects the puhiic heaith by
`assuring the safety, effectiveness, and security of human and yeterinary drugs, vaccines and other
`hioiogicai pro-ducts for human use, and medicai devices. The agency aiso is responsibie for the safety and
`security of our nation's food supp-iy, cosmetics, dietaiy suppiements, products that give off eiectrc-nic
`radiation, and for reguiating tobacco products,
`
`#
`
`wwm/.fo'e.g o\.4i\i ews "Events/N ens room’Press/innourcements/ucrnz‘": 7833. htm
`
`1,/2
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 11
`
`

`
`S/4.v’13
`
`Press Announcenmnts; > FDA approves newvtreatnxent for 2: type of late; stage rcmzatez cancer
`
`"lead cur 330;}:
`
`\»"ai::<2‘q'
`
` Visit the
`am F;=.~r_:eb:m§<5r§?,
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`RSS3 Feed for FE»!-\ §\:e.w:; §‘x‘s=_eEe.ases"-‘3
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`1“;
`.
`
`v
`
`U.S, Focwci and Drug Administa'ati0r:
`10903 New Harnpshire Ax/anue
`Siiver Spring, ME: 20993
`Ph. 1—888~I!\3FO—FDA (1—888~463«6332)
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`
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`E3°.‘*‘E3‘E—"
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`,"Drugs_/Rest»urcesFoa'YoL:;’Consumers,r’uc m£3S4420, htm
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`httpzf, mxrwJfda.gov,’DrugsfDaveioprnentAppr‘o\:aiPr'<>c<=:ss;’Drug1nn<>vation/defauit. him
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`https :,:’;’ biogaafcise .g<>v;'fda\:c:Ece,«’
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`httpzf, mvw.fEE<';E<r.com,iphotos,ffdaphotosf
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`i*zi:'t;>:,",’wv\rwfda.govmbout.FD:fxfAbouE'TE1i5‘v’\iebsite,»’V\!ebsit.efiaiiciesfbisciaimers,r’defauiii.him
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`10. ht:'tp:,",’-mvxrwfda.govmbout.FfifixfccntactFDA,»'S‘i:.ayInformed,»’RSf5Feeds;'PressReieasesfrss.><mE
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`www.fda.g OV/N ews Events/N -em room’Pres3/innoumements,/ucmz‘": '/833.htn1
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 12
`
`

`
`5/4413
`
`Press Aonouncernents > FDA Approves New Treatment for Advantzed Prostate Cancer
`
`
`
`Archived Qontent
`
`The content on this page is provided for reference purposes oniv, it was current when
`produced, but is no ic-nger maintained and may he outdated,
`
`
`
`\: ,\, we <3 es, . . cw.‘
`
`EBA NEWS RELEASE
`
`For immediate Reiease: June 1?‘, 201:’)
`Media Enquiries: Erica .it=:fft-arson, 3t'i1~79-6- 4988,
`fionsisrner Enquiries: 888—Ii‘iFO—Fi3:A
`
`
`
`FBA Approves New Treatment for Advanced Prostate flancer
`
`The US. Food and Dru-:3 Administration today approved Jevtana {<:ahazitaxei), a chemotherapy drug used ii‘
`combination with the steroid precinisone to treat men with prostate cancer, Jevtana is the first treatimnt
`for advanced, hoi'inone—retractorv, prostate cancer that has worsened during or after treatment with
`ciocetaxei, a <:omn"=oriv used drug for advanced prostate cancer,
`
`In prostate cancer, the rnaie sex, hormone testosterone can cause prostate tumors to grow, Drugs, surgery
`or other hormones are used to reduce testosterone production or to hiock it, Seine men have hormone
`refractory prostate cancer, meaning the prostate cancer ceiis contintie to grow, despite testosterone
`suppression. Different treatments are needed for men with this type of cancer,
`
`Jevtana was reviewed under the FDA’s priority review program, which 335'-:3‘v‘idEES for an expedited si><~ month
`review for drugs that may offer major advances ir treatment, or provide a treatment when no adequate
`therapy exists, Jevtana received approvai ahead of the product's Sept, 30, 20112), goai date,
`
`iVi.i?-,, director of the
`“Patients have few therapeutic options in this disease setting,” said Richard Pazdtir,
`Citfice of Oncoiogy Drug Products, part of the FDA’s Center for Drug Evaioation and Research. “FDA was
`ahie to review and approve the appiication for Jevtana in 11 weeks, expediting the avaiiahiiity of this drug
`to men with prostate cancer,”
`
`,ievtana’s safety and effectiveness was estabiished in a singie, ?SS~patient study. Aii study participants
`had previoasiy received tioceitaxei. The study was designed to
`overaii survivai {the iength of time
`before death’) in men who received Jievtana in cr_>n“it_iinatien with prednisone compared with those who
`received the chemotherapy drug, niito><anti'-one, ir combination with prednisone. The median -3-veraii si.irviva§
`for patients receiving the ievtana regimen was 15,1 months compared with 12.7 ironths for those who
`received the mitoxantrone regimen.
`
`Side effects in those treated with Jevtana incitided decrease in infe<_:ition~'fight:in<3 white hiood ceiis
`ineutropeniai, anemia, decrease in the number oi‘ white hiood ceiis (ietikopenia), iow ievei of piateiets in th
`hiood {thromhocvtopenia), diarrhea, iatigtie,
`vorniting, const.ipation, weakness (asthenia), and ten;
`Failure.
`
`is the second most common cancer among rren in the
`Prostate cancer, which iisuaiiy occurs in oider men,
`Linited States, behind skin cancer. in .3?.:.’_‘;i_i6, the most recent year for which numhers were avaiiabie,
`.?~?.ti3,4i5 men deveioped prostate cancer and 2.},.372. rnen died from the disease, according to the Centers
`for
`Centre! and Prevention.
`
`Jevtana is marketied by Sridgewaiier, i\i.}.~hased Sanofidwenitis.
`For more information:
`
`
`
`wwn/.fde.g o\.ii\i ews "Events/N ewe room/Press/mnoumernents/ucrn2'i
`
`1 4.3. him
`
`1,/2
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 13
`
`

`
`5/4413
`
`Pram Aairzcnuncxarrvents > FDA Approves New Treatment for Advancetii Prostate Czsncezr
`
`Page Last Updated: O4,/23,»’2£313
`
`n U
`
`am-:E Dang Administratican
`N. F-.,-«:2
`13903 New Hampshire I-wemae
`Siiver Spring, MD 23993
`Ph.
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`Links an this page:
`1. httpzf,/www.fda.gov,"AboutFDfixféiiea*:tersOffices,/CDER;'ucmD91745,htm
`
`Ex) http:,’,/wvw.'.cdc .govfcam:er]prostate/informeajmdec isionmmaking , htm
`
`U2
`
`http:/,/www..cancar,g«3v,/cancartopicsftypesmrostate
`:‘-‘* http:/,iwww ..fda.gcn:,’Abo utFDA/ContactFDA,r’Stay1nf<:» rmed;’RSSFeeds/Pa'ess Rezieasesf rss.>-zmi
`Ui
`
`http:/,/www ..f::ia.gcn:/Abs utFDA/C0r:tactFDA,r’Stay1nfc» rmed,/RSSFeeds/uc m144S7S.htm
`
`www.fda.g OV/N ews Events/N -em room/Press/mnoumements/ucm2'i £»14.3.htm
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 14
`
`

`
`8/441 3
`
`Press Anri.<:-uncemenis > FDA expancis Z‘,¢.iga‘s use for Ieatestzagie
`
`<:an(:er
`
`
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`FEA NEWS RELEASE
`
`Fer immediate Reiease: Dec. 10, 2012
`Media Enquiries: Stephanie ‘rah, 301—796—0394,
`tfianstsrrser Enquiries: 88i'£~ti\iFt’3—FDA
`
`
`
`Fee expands Z'e,,itiga’s use fer iate-stage arestate cancer
`Drug can new be used before treatment with chemotheraizay
`
`The US, Foati and Drug Adrninistraticrn today expantied the apt:-raved LESE -af Zytiga (ahiraterone acetate)
`to treat men with iate~stage {metastatic} -:astratiori—resistant terestate can-cer prior to re<:eiv‘ing
`ehemetiierapy.
`
`The FDA initiaiiy approved Zytiga in Aprii 2011 for use in patients whese prostate cancer rsregressed after
`treatment with docetaxei, a chemotherapy drug. Zytiga is a piii that tie-creases the prodactien of maie sex
`hermone testosterone“
`
`In prostate cancer, testcisterorie stimuiates r.ir-3-state tuiriors to gr-::>w. Drugs or surgery are Lise-::i to reciuce
`testosterone prodtisticih or to biOCi~‘; testoster-::2ne’s effects. Some men have <:astratii:>h—resistant arestate
`-earicer, meaning the prostate caricer ceiis centihue ta grow even with iow ieveis of testosterone.
`
`“Today/’s apgrirevai ciemcznstrates the benefit of further evaiuating a -cirug in an eariier disease setting anti
`provides patients arid health care proviciers the eptien of using Zytiga eariier in the course -at treatment,”
`said Richar-2i Pazdur, ii/i,D., director of the Office of Cinccsiegy Drug Pi’-J-CiLiC‘iiS in the F[.TA’s Center for E3-rug
`Evaiuatiori and Research.
`
`The FEE»!-\ reviewea Zytiga’s arxpiizgatiran for t.his hew ii‘iCii<.‘.i."3i.',if_?i’i under the agen<;y’s ririariiy review program.
`The program ;’>FOVid€5
`for an e;<pediteri six—mohth review for drugs that
`after major aejvaraces in
`treatment or previde a trea'trneht when new atieqtiate therapy exisiis.
`
`ciiriictai study of 1,088 men
`Zyti<_.;a’s sai‘et.y and eiieciiiveraess far its expanded use were estahiishea ir:
`with iate~stage, cast.ratienuresistan't prostate cancer who had not rirevinusiy receiveti chen”r.>iiherar:‘,i.
`Participahiis received either Zytiga er
`piacehe (sugar piii) ir: eembihaiiien with prednisone.
`
`The study was ciesigheci to measure the iength at time a patient iived hefsre death (averaii survivai} and
`the iength of time a haiiienii iived without further "turner growth
`assessed by imaging siitidies (radiograhhi
`progression-"free siirvivai, er rPFS).
`
`Patients wha i'et;t=,=iveti Zytiga had a median averaii suiwvai of 35.3 rrionths compareti with 30.1 months for
`those re<:eiving the piazieha. Study resLiit:~: aiso showed Zytiga iihpi‘o'v‘ei:i rPFS. The median ri>FS was 8.3
`months in
`hiaceho group and had not yet been reat;heti far patients treateci with Zytiga at the time at
`anaiysis.
`
`The mast conirrioh side etieicts reported in these receiving Zytiga ii‘ii'.'ii.iCii‘: fatigue, joint sweiiing car
`<;iist;erriftirt, sweiiing caused by fiuiti retention, hat fiush, tiiarrhea, vomiting, cough, high hioeti pressure,
`shortness of hreath, urinary‘ tract infection, arid hitiisang.
`
`The most cemrhen iahorat-3-ry ahnermaiities inciutied iow red hiooci ceii CC:-Liiit; high Eeveis at the enzyme
`aikaiine phosphatase, which can he a sign at ether serious medicai prohiens: high ieveis of fatty acids,
`sugar, and iiver enzymes in the bioaci; anti iow ieveis at iymi:-hocytes, phosphorous anti potassium in the
`hiooci.
`
`Zytiga is marketed hy iiarsham, Pa,~hase=:i Janssen Si-3-tech inc.
`For i’i’iC-FE irifcsrrnatioh:
`
`
`
`this press reiease was updated an flee. 16:23, .2G1.;‘ at 2:39 gem. te eerreet the date when zytiga was
`
`www.fa'e.g OV/N ewe Events/N ens roomlPress/innoumements/ucm;‘;‘1 492. him
`
`1,/2
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 15
`
`

`
`5/4.v’1 3
`
`Press AI’lf‘.(3L1:”!()E3f'F‘K3n"-ES > FDA eqaancis Zyiig; 21's use for |ate~st2age
`
`czeancer
`
`eriginaiiy appravegi its Aprii JEQEE.
`
`The FDA, an agency within the U.S. Department of Heaitn and Human Services, protects the pubiéc heafith
`by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and <:>ti':er
`bi-3-Eogieai pi‘c:--ziucts fa:-r human use, anti medics! cievices. The agency aiso is respensibie fer the safety‘ and
`security Of -3-ur nation's feed supp-fly’, cosmtics, dietary suppfienwents, products that give off eiectr-3-nit:
`radiatée-n, and for reguiating tCrbEiCCC% ;3E‘<3dUCtS,
`
`if
`
`Read our Biog:
`
`FET;=:.\ v.::;:e.=5
`
`Visit; the
`
`an Fac:=2b:_:oE~«:5r§‘,
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`Q
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`f-“eeci for me: News §%ieEea=:sa=:s11
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`Page Last up-ziate-:E: 12/1C:/_2C312
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`U.E». Food and Drug A’-\(iE"i’ii:"1§S‘l',i“E.i'?.'§('}:’1
`182-“:03 New Hampshire Avenue
`Siiver Spring, Wit} ZGQEE3
`\
`Ph. 1-338-INF€3-FDA (1-888-463-6332)
`.\
`
`
`
`Linke an this page:
`1.
`/i\Eew5EventsjNewsrm.>m;’PressAnn:3unc:amen'ts5jucm2.53OE55.htrn
`
`2.
`
`,r’Abr3utFDA/Ceriters5OFFices,»’C)iFiFie:eo'fMedEs;aiProciuctsandTr3bac:r_::3/Cf3ER,fu<;mO91745.htm
`
`/Dri.i;_;;$,"Resoi.irce5FerYou,/Cons5Lirnei“s,»’LicmiJS442O.htm
`
`-V’-‘E, http:/;"Nww.cancer.gevfcam:ert<:>pics,/typee./prostate
`
`U"!
`
`hit :33 :/‘,1’ biogs , fda ,gov,/fdaveEce,r’
`
`http : ;’;'w'ww.facebooi<. c»:sr*s/FDA
`
`F39‘ http;/iwww.fEEeE<i:eem,1photes/fdaphotos,’
`
`S3’
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`‘~.C.3
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`I‘-* C)
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`i*:tt;3:;’;'www nyotituiae,<2om;’user,/USFoociandbrugfitd min?b!em:i=23&ob=5
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`http:/itwitter,com,’us___fda
`
`httgaz/;’www .fda.g<:2v;'AE:rcrutFDA,"AboutThiswebsitefvkiebsitePoiicies,"Dis<: iaimerwdefauit, htm
`
`11, http:;’,’w‘ww.fda,g«:2v;’AE:w:rutFDA,"Contai:tFDA/Staylnforme::ifRSSFeeds;’PressReieasesirss..><mE
`
`www.fda.g OV/N ewe Events/N -ems room’Pres3/innoumements,/ucm;‘;‘1 492. him
`
`Kw
`
`MYLAN PHARMS. INC. EXHIBIT 1012 PAGE 16
`
`

`
`Z‘i’TitiA® la hiraterone acetate} Ta islets
`
`-----------------------------WARNENGS AME} Pl§EEJAUTiQNS»--~--~--~--~--~-~~-~--~--~~-
`8 lviineralocorticoid e
`ss: Use }:'YTlGA with on
`in patients with a histon;
`
`
`
`of cardiovascular
`.ase. The safety oi‘ ZYl'lGA in patients with LVEF < 50% or
`N‘i’ii/‘t Class ill
`lV heart failure in Study i or LVEF < 50 "/0 or i\i‘{HA Class ii
`to EV heart failure in Study 2 was not estaiaiished. Control hypertension
`correct
`iavrrekalemia before treatment.
`ivlonitor blood pressure,
`seruin
`potassium and syrnptnms of fluid retention at ieast rnonthiy. (5.1)
`of
`signs
`a Adrenocorticai
`insufficiency: Monitor
`tor
`symptoms
`and
`adrenocoiticai
`insufficiency.
`increased dosage of corticosteroids may be
`indicated before, durinij and after stressful situations. (5.2)
`liepatottrxicitv: lrrcreas-L
`liver enzvrrres trail
`‘ to drug interruption, dose
`
`
`inodiiieation and/or disco: nuatiori.
`ivionitor
`liver
`function and modihr,
`interrupt, or discontinue ZYTEGA. dosing as recommended. (5.3)
`a Food effect: Z‘i’l'li_-‘LA must be taken on an empty stomach. Exposure (area
`urirler the curve) of ahireterone increases up to it) told when abiraterrine
`acetate is taken with ineais. (5./ii
`——————————————————————————————————- AEIVEHSE REACTEONS——-—-~—-~--~—--~-----—-~--—--—-~--~
`The most corrrmorr adverse reactions (2 lO%_l are tatigiie,
`ioint sweiling or
`discomfort, edema, not flush, diarrhea, vorniting, cough, hypertension, dysprien,
`urinary tract infection and contusion.
`
`as
`
`The most common laboratory a"ononnaiities (> 20%) are anemia, elevated alkaline
`
`phosphatase, hypertrigiy-seridernia,
`lymphoperiia, hyperchelester-r
`“Ea, hyper-
`glycemia, eievated AST, hvpophesonatemia, elevated ALT and liynokalemia. (6)
`
`Jirurissen Biotech,
`E-flit}-FEBA-~i(}38
`or
`
`SEJWEEZTEEE ABVERSE REAtITii}NS. contact
`regmrt
`To
`at
`i-Sm)--528--3735
`€’l-vfliifi-JANSSENE
`or
`FBA at
`inc.
`wwvtnftfayov/rrreaiwaich.
`-----------------------------------Biitfifé ii\lTEFEA(§Ti0t\ri$
`Z‘r"llGA is an inhibitor of the hepatic drirg»-metabolizing enzyrne t‘.‘rP2D8. Avoid
`CD-EL...
`istration of Z‘i’TlG.I’-\. with E"i’P2D’d sutrstrates
`that have a
`riarrow
`
`therapeutic index.
`it an alternative treatment c
`ot be used. ex ‘
`e caution
`
`and consider a dose reduction of the
`C‘iI'i’2{‘i6 substrate. (7)
`————————————————————————————— USE iitl SPECEFEC POPULATEGMS »————————————————»——»——»—————
`
`
`
`a Do not use Z‘;/TEGA in patients with baseiine severe hepatic lmpairrrrerrt (Ci-.ile'—
`Pugh Class C}. (8.6)
`
`See ‘i? for Patient Ceunseiing information and Fi)A—appmved patient iabeling.
`
`Hifii-ii.il¥H'i':‘.§ QF Pl’-iE${2§‘tiE3ii\ifi ii\iF{3l'-iMiTtTi{3i\i
`‘these highlights rte net inciude alt the informatien needed to use ZYTEGA saieiy
`and effectiveiy. See iuii prescribing inferrriation tor ZYTEGA.
`
`Z“§’"E'EGA®
`iahiraterone acetate} Tablets
`
`For flrai Adrniiiis‘-lratiorr
`
`Enitiai i.i.S. Aprirovai w 291?
`
`gggggggfr Mfijgfi r;i.§m\gr;E5...................
`
`indications and usage (ti
`Contraindications, Pregnancy iii-.il
` lcnlrl excess (fill
`Warnings and Precautions. :’\Jlineraioco'
`Warrrin