`
`CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`21-660
`
`ADMINISTRATIVE DOCUMENTS
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 1 of 102
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`Actavis - IPR2017-01101, Ex. 1016, p. 1 of 102
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`

`

`American BioScience, Inc.
`
`N21660
`
`American BioScicncm Inc.
`
`Patent Certification
`
`Paragrth II Certification
`
`In the opinion and to the best knowledge of American BioSeience, 1110., there are-no
`
`unexpired patents nun claim the listed drug ['[‘axoi® (paelitaxel) Injection] referred to
`
`in this application or that claim a use of the listed drug.
`
`Mitchall G. Clark
`
`Date
`
`Vice President, iitguiatory Affairs
`
`2730 Wilshire Blm.. in}. u: 110 Santa Monica, California 90403 Tel: (310) 883-1300 Fax: (310) 998-8553
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 2 of 102
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`Actavis - IPR2017-01101, Ex. 1016, p. 2 of 102
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`

`

`
`
`American BioScience. Inc.
`
`N21660
`
`-
`z
`Department of Health and Human Services
`Food and Drug Adn'unrstration
`PATENT INFORMATION SUBMITTED WITH THE
`FILING OF AN NoA, AMENDMENT, 0R SUPPLEMENT
`For Each Patent That Claims a Drug Substance
`(Active Ingredient), Drug Product (Fonnuiation and
`Composition) and/or Method of Use
`
`Form Approved10MB No. 0310-0513
`wmmn Dam: 07mm
`s” OMB Mmmm Page 3‘
`N... NUMBER
`
`NAME OF APPLICANT I NBA HOLDER
`American BioScicnoe. [no
`
`The following is provided in accordance with Section 505(k) and (c) of the Federal! Food. Drug. and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME}
`AbraxaneTM (nab Paclitaxet) for in] ectable Suspension
`ACTIVE INGREDIENHS]
`Paclitaxel
`
`STRENGTHtS}
`100 mg/vial
`
`DOSAGE FORM
`Sterile powder for injectable suspension
`
`required to be submitted to the Food and Dmg Administration (FDA) with an NBA application.
`This patent declaration form is
`amendment. or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53(d)(4}.
`Within thirty (30) days after appmval of an NBA or supplement. or within thirty (30) days of issuance of a new patent. a new patent
`declaration must be submitted pursuant to 21 CFR 314.53tc)(2)(ii) with all of the required information based on the approved NDA
`or supplement. The information submitted in the declaration torm submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Book.
`
`For hand-written or typewriter versions (only) of this report: It additional space is required for any narrative answer (i.e., one
`that does not require a "Yes‘ or "No" response). ptease attach an additional page referencing the question number.
`FDA Witt not iist patent information if you rite an incomplete patent declaration or the patent declaration indicates die
`patent is not eitgibie for listing.
`
`For each patent submitted for the pending NBA, amendment. or supplement referenced above, you must submit all the
`infon'nation described beiow. if you are not submitfing any patents for this pending NBA. amendment. or supplement.
`tote above section and sections 5 and 6.
`
`a. United States Patent Number
`6,537,579
`d Name 0! Patent Owner
`American BioScience, Inc.
`
`V
`
`b. issue Data of Patent
`3/25/2003
`Address (of Patent Owner)
`2730 Wilshire Boulevard, Suite 110
`
`-
`
`c. Expiration Date ref-Patent
`2/221'2013
`
`‘
`
`
`
`Cityistate
`Santa Monica, CA
`ZIP Code
`90403
`
`Telephone Number
`3 ID 883 1300
`
`FAX Number (ifevaiiebie)
`3 to 998 8553
`
`E-Mail Address (iiavariabia)
`
`e. Name at gent or repmggglatiy who resides or maintains Address (ofagonl ormprasentativa namedin 1.5.)
`a place or business within the United States authorized to
`receive notice of patent codification under section
`505(b)(3} and (j)(2)(B) of the Federal Food, Drug. and
`Cosmetic Act and 21 CFR 314.52 and 314.95 (it patent
`owner or MBA applicantiholder does not reside or have a
`place of business within the United States)
`
`CWSME
`
`G:
`
`Telephone Number
`
`FAX number (ifsullen”)
`
`E—Mail Address (it availabia)
`
`t.
`
`Is the patent referenced above a patent that has been submitted previously for the
`approved NBA or supplement referenced above?
`g lithe patent referenced above has been submitted previously for listing. is the expiration
`date a new expiration date?
`
`FORM FDA 3542a (7103)
`
`Page 1
`PSC Ml!" Maul) NJ-Im EI’
`
`
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 3 of 102
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`22
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`Actavis - IPR2017-01101, Ex. 1016, p. 3 of 102
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`

`

`American BioScience, inc.
`
`N21660
`
`For the patent referenced above, provide the following information on the drug substance, drug product andfor method of
`use that is the subject of the pending NBA, amendment, or supplement
`
`_
`..
`7.
`.
`.
`2 Sim insure. their" Ins”; int) "
`2.1 Does the patent ctaim the drug substance that is the adive ingredient in the drug product
`described in the pending NBA. amendment, or supplement?
`2.2 Does the patent stain-t a rim substance that is a different polymorph ol' the active
`ingredient described in the pending NBA. amendment. or supplement?
`2.3 It the answer to question 2.2 is "Yes." do you certify that, as of the date of this declaration. you have test data
`demonstrating that a dmg product containing the polymorph will perfon-n the same as the drug product
`described in the NBA? The type of test data required is described at 21 CFR 3.1453(1)).
`2.4 Specify the polymorphic torm(s) claimed by the patent forwhich you have the test results described in 13.
`
`C] Yes
`
`2.5 Does the patent claim only a metabolite oi the active ingredient pending in the MBA or supplement?
`(Complete the information in section 4 below if the patent claims a pending method of using the pending
`drug product to administer the metabolite.)
`2.6 Does the patent claim only an intennediate?
`
`D Yes
`
`{Xi No
`
`2.7 if the patent referenced in 2.1 is a produd-by-prooess patent. is the product claimed in the
`patent novel? (An answer is required only it the patent is a produd-hy-process patent.)
`
`3.;Di'ug Productlico'inpositionlfiontfuietton)
`3.1 Does the patent daim the drug product. as defined in 21 CFR 314.3, in the pending NBA,
`amendment. or supplement?
`3.2 Does the patent claim only an intermediate?
`
`3.3
`
`it the patent referenced in 3.1 is a productvbyprueess patent. is the product claimed in the
`patent novel? (An answer is required only it the patent is a product—hymns: patent.)
`
`r:
`
`..--
`
`
`
`,‘M'
`‘
`"
`: “
`_.
`_
`4
`‘
`4. Method orus'e
`‘
`Sponsors must submit the information in section 4 separetely hr each parent claim claiming a method of using the pending drug
`product for which approval is being sought. For each mottled of use claim referenced. provide the following information:
`4.1 Does the patent claim one or more methods of use tor which approval is being sought in
`the pending NDA. amendment. orsuppiemenl?
`L2 Patent Claim Number (as listed in the patent)
`[.6‘ 10.| 5. 22.27, 3{J.421 49.5|
`
`E Yes
`Does the patent cla‘m referenced in 4.2 claim a pending method
`cl use fwwhlch approval is being sought in the pending NBA,
`amendment. or supplement?
`E Yes
`
`[I No
`
`D No
`
`FORM FDA 3542a (HOS)
`
`Page 2
`[scou- mlm|)ut-tose
`EF
`
`
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 4 of 102
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`23
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`Actavis - IPR2017-01101, Ex. 1016, p. 4 of 102
`
`

`

`American BioScience. inc.
`
`N21660
`
`i
`
`‘18 ltthe answer to 4.2 is
`"Yes." identify with speci‘
`ticity the use with rater-
`enco to the proposed
`labeling for the drug
`product.
`
`ormethod or use infonnation as identified spectfieeiryr'n die approved labeling.)
`Use: (Submit
`Claims 10-15 - Abraxane (neb paclitanet) tor inieetable suspension is a nanoparlicle albumin-bound (nab) term of
`paclitaxel. See Description. Each single-use vial corneins 100 mg oi pacfltexel and approximateiy 900 mg of human
`albumin. See Decent)”. ‘I'l'u's ion'nulation is tree from solvents. See
`Abmxane (nab paciitaxel) for
`injectable suspension is indicated for the treatment effluent cancer. See indication. Abraxane does not
`contain Cremephor-EL. therefore hypersensitivity rea on! Abraxane are rare. See Adverse Reectr'ms:
`Hypersensitivity Reactions (HSRs). For metastatic breast cancer. Abraxane (nab pacl‘rtexei tor irrieclable suspension)
`at a dose of 260 nrgima administered intravenously over 30 minutes every 3 weeks has been shown to be effective.
`Sea Dosage and Administration.
`
`Claims 22-27. 32-34. 39-42. and 49.51 - Abmxane (nab pactitaxel) for iniectnbie suspension is a nonoponicle albumin-
`bound (nab) form of paditaml- See
`Abraxane is suppfied as a white to yellow. sterile. Iyophlilzed provider
`intended for reconstitution whh 0.9% Sodium Chloride intention, USP prior to intravenous infusion. See Descrbtion.
`Each singleme vlel contains 100 mg of paciitaxel and approximately 900 mg of human atbumln. See Description.
`Abraxane (nab paciilaxel) for injectable suspension is indicated tor the treatment of
`breast cancer. See
`indication. For metastatic breast cancer. Abraxane (nab paciitarret for lniemable suspension) at a dose of 260 mgtm‘
`administered intravenously over 30 minutes every 3 weeks has been shown to be otlective. See Dosage and
`Administration. Abraxane is supplied as a sterile tyophlfized powder for reconstitution before use. See Dosage and
`Administration: Preparation for intravenous Administration. Reconstitute each vial by injecting 20 mL of 0.9% Sodium
`Chloride Iniectiorl. USP. $90 003599 and Administration: Preparation for intravenous Administration. Each mL oi the
`reconstituted nanoparticte formulation will contain 5 mgimL paciitaxel. See Dosage and Administration: Preparation for
`intravenous Administration.
`
`
`
`Claim 30 - Abraxane [nab paclitaxei] for iniectabie suspension is a nancpanicle aibuntin—bound (nab) term oi paciitaxel.
`See Descnpuon. Each single-use vie! contains 100 mg of pactitaroel and apprordmatety 900 mg of human albumin.
`See Description. This formulation is he from solvents. See Description. Abraxane (nab paclitaxel) tor lniectabie
`suspension is indicated for the treatinth at
`most cancer. See indication. Neulrcpenia. the most important
`hematologic toxicity. was dose dependent and was generally rapidly reversibte. See Adverse Reactions: Hematologic.
`Grade 4 (<50!) cellslmm’) neutropenia occurred in 12% of patients treated with Abraxane. See Adverse Reactions:
`Hematoiogic. Among patients treated in the Phase 3 metastatic breast cancer study. neutrophii counts declined below
`500 ceiisr‘mm' (Grade 4) in 9% of the patients treated with a dose of 260 mgi'm‘ compred to 22% in patients receiving
`Cremaphor~based paclitaxei Injection at a dose of 175 motor“. See Adverse Reactions: Hematologic. Among patients
`Abraxane does not contain Cremophor~EL. therefore hypersensitivity reactions to Abraxane are rare. See Adverse
`Reactions: Hypersensib'viry Reactions (HSRs). For metastatic breast cancer. Abraxane (nob paciitaxel tor injectabio
`suspension) at a dose ct 260 mgiiri2 administered intravenousty over 30 minutes every 3 weeks has been shown to be
`effective. See Dosage and Administration. AbraxarIe is supplied as a sterile lyophitized powder for reconstitution
`before use. See Dosage and Administration: Preparation for intravenous Administration. Reconstitute each vial by
`intactng 20 mL of 0.9% Sodium Chloride Inlection. USP. See Dosage and Administration: Preparation forintravenous
`Administration.
`
`Claim 31 ~ Abraxane (nab paclitaxel) tor injectable suspensioniis a nanoparticle alburnirr-bound (nan) term oi
`paclitaxet. See Description. Each singie-use vial contains 190 mg of pacittaxel and approximately 900 mg of human
`albumin. See Description. Abraxane (nab paclitaxali tor injeclabie suspension is indicated for the treatment oi
`misread cancer. See indication.
`in general. the frequency and severity of neurologic manifestations were
`as
`ependent in patients receiving single-agent Abraxane. See Adverse Reactions: Neurologic. Peripherat
`neuropathy was observed in 64% of all patients (10% severe). See Adverse Reactions: Neurologic. Peripheral
`neuropathy was the cause of Abraxane discontinuation in 131366(4%)ot all patients. See Adverse Reactions:
`Neumtogr‘c. Sensory symptoms have usually improved or resoived within 22 days or interrupting Abram therapy.
`See Adlrerse Reactions: Neurologic. Pro-existing neuropathies resulting from prior therapies are not a contraindication
`For Abraxane therapy. See Adverse Reactions: Neumlogic. No incidences of grade 4 peripheral neuropathies were
`reported in the clinical trial. See Adverse Rsections:Naumiogic. Other than peripheral neuropathy. serious neurologic
`events following Abruane administration have been rare (<1%) and have hrcludod ischomic stroke. metabolic
`encephalopathy. contusion. dinlnessilightheadedness. and mood alterationldepression. See Adverse Reactions:
`Neurotogic. For metastatic breast cancer. Abraxane (nab paclilaxel tor lnjectebie suspension) at a dose cl 260 mgim’
`administered intravenously over 30 minutes every 3 weeks has been shown to be eitective. See Dosage and
`Administration. Abraxane is supplied as a sterile lyophitized powder for reconstitution before use. See Dosage and
`Administration: Preparation for intravenous Administration. Reconstitute each via! by injecting 20 mL at 0.9% Sodium
`Chloride Injection. USP. See Dosage and Administration: Preparation farintravenous Administration.
`
`FORM FDA 3542a (NOS)
`
`Page 3
`55C Mull: moonlit-rm F5
`
`
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 5 of 102
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`24
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`

`

`American BioScience. Inc.
`
`N21660
`
`4.2a it the answer to 4.2 is
`“leaf idanlifv grim wed-
`flow “it-'- “33 "'9' ram“
`ance‘ 1° W proposed
`IaMINI for the drug
`Product
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ormethod of use infon'nation as identified specificaily in the approved labeling.)
`Use: (Submit
`Claims 36 and as -Abraxane (nab paoiitaxet) for irijectabte suspension is a nanopartiete albumin-bound (nab) form of
`paclitaxel. See Description. Abraxene is supplied as a while to yellow. sterile. tyophit'ized powder intended for
`reconstitution with 0.9% Sodium Chloride Intection. USP prior to intravenous infusion. See
`Each single-
`use vial contains 100 mg of paclitanet and approximately 900 mg of human albumin. See Description.
`Two studies were conducted in 106 patients previously treated with a maximum of one prior chemotherapeutic
`regirrien. See Clinical Studies: Breast Cenfinoma: Phase 2 open label stuo'i‘es. Abraiiane was administered in these
`two trials as a 30 minute infusion at deeds of 175 rngtrn’ or 300 mph“ withont steroid piemedioation or planned G-
`CSF support. See Clinical Studies: Breast Carcimrna: Phase 2 open label snrdies. Antenna (nab pactitexel tor
`injectatile suspension) is indicated for the treatment of “breast cancer. See indication. For metastatic breast
`cancer. Abraxane tneb-pectitaxel for injecleble suspension) at a dose of 260 mgkn2 administered intravenously over 30
`minutes every 3 weeks has been shown to be effective. See Dosage and Administration. Abraxane is supplied as a
`sterile lyophitized powder for reconstitution belore use. See Dosage and Adminlsb'atlon: Preparation forlntrewnous
`Administration. Reconstitute each vial by inhaling 20 mL No.91: Sodium Chloride Inledlon. USP. See Dosage and
`Administration: Preparation for intravenous Administration. No premedioation is required prior to the administration of
`Abraxane. See Dosage and Administration: Preparation and Adminishetion Precautions.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`-
`'
`5. No Relevant Fatents',
`For this pending NDA. amendment. or supplement. there are no relevant patents that claim the drug substance (active ingredient).
`drug product (formulation or composition) or method“) of use, for which the applicant ls seeking approval and with respect to
`
`[3 YES
`which a claim of patent infringement could reasonably be asserted ifa person not licensed by the owneroftiio patent engaged in
`
`the manufacture. use. or sale ofthe drug product.
`6. nectaridonttaiifldcsil‘dn
`6.1 The undersigned declares that this is an accurate and complete submission ofpatent information for the NBA.
`
`amendment, or supplementpending under section 505 of the Federal Food, Drug. and Cosmetic Act. This time-
`
`serrsldve patent lnfonnatr‘on is submittedpursuant to 21 CFR 314.53. lattes: that i am familiar with 2! CFR 314.53 and
`(tits submission complies with the requirements of the regulation. lverlfy under penalty olperjury that the foregoing
`
`is true and correct.
`
`Warming: A willfully and knowingly false statement is a criminal offense under 18 U.S.C. 1001.
`Date Signed
`6.2 Authorized Signature of NBA ApplicantlHolder or Patient Owner (Attorney. Agent, Representative or
`
`other Authorized Official) P w ' e
`lnl'm‘mali'On below)
`
`Biosciencc. inc.
`Patrick Soon-Shiong, M ,
`
`
`/3 MM;
`ay submit this declaration directly to the FDA. A patent owner who I; not the NDA eppltcantl
`NOTE: Only an NBA applicanttttolder
`holder is authorized to sign the declarat in but may not submit It directly to FDA. 21 CFR 314.5333“) and (dim.
`
`
`
`
`
`
`
`
`
`
`C] NDA Applicant'slHolder‘s Attorney. Agent (Representative) or other
`Authorized Official
`
`
`
`I3 Patent Owners Attorney. Agent (Representative) or Other Amhorized
`Official
`
`CityiSlate
`Santa. Monica. CA
`
`Cheek applicable box and provide information below.
`
`E NDA Applicant/Holder
`
`
`
`
`
`[:| Patent Owner
`
`_
`Name
`American BioScience, Inc.
`Address
`2730 Wilshire Boulevard. Suite llti
`
`
`
`
`
`ZIP Code
`90403
`
`FAX Number (if available)
`310 998 8553
`
`
`
`Telephone Number
`310 833 1300
`
`E—Mail Address (if available)
`
`FORM FDA 35423 (7103)
`
`Page 4
`ester-ti. Arum” eds-ion
`E?
`
`
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`Actavis - IPR2017-O1101, Ex. 1016, p. 6 of 102
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`Actavis - IPR2017-01101, Ex. 1016, p. 6 of 102
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`

`

`American BioScience, Inc.
`
`N21660
`
`An agency may not cmduct or sponsor, anda person is no! nquired to n1pand'ro. a collection of
`
`including the (Em: for reviewing
`lhis coilection of infotmuion has been estimated to Iva-age 9 hours per response.
`Th: public reporting burden Ibu-
`instructions, searching wining data sources. gathering and maintaining the dun needed. and oomph-fins and miewiug the collection of infirm-(ion. Send
`mt; reg-Ming this burden urinate or my other aspect oflhis cullnclion ofhibernation. including suggestions for Iuiucing this burden to:
`Food and Drug Administration
`CDER (HFMOT)
`5600 Fishcrs Ian:
`Roclwille. MD 10857
`
`infirmflau auricu- ir displaysa cmdy valid OMB control number.
`
`FORM FDA 3542a {1:03)
`
`Pa e sa
`PSC Mdil Magnum-1w EF
`
`
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 7 of 102
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`26
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`Actavis - IPR2017-01101, Ex. 1016, p. 7 of 102
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`

`

`American BioScience, inc.
`
`N21660
`
`INFORMATION AND INSTRUCTIONS FOR FORM 3542a
`
`PATENT INFORMATION SUBMITTED WITH THE FILING
`OF AN NDA, AMENDMENT OR SUPPLEMENT
`
`describes the authorized signature.
`
`General Information
`
`information to the agency the appropriate
`0To submit patent
`patent declaration form must be used. Two forms are available
`for patent submissions. The approval status of your New Drug
`Application will determine which form you should use.
`patient
`a Form 3542a
`should
`be
`used when
`submitting
`information with original NDA submissions. NDA amendments
`and NBA supplemean prior to approval.
`
`supplemental
`IForm 3542 should he used after NDA or
`approval. This form is to be submitted within 30 days after
`approval of an application. This form should also be used to
`submit patent
`information relating to an approved supplement
`under 2] CFR 314.53(d) to change the formulation, add a new
`indication or other condition of use, change the strength, or to
`make any other patented change regarding the drug, drug
`product, or any method of use.
`
`oForm 3542 is also to be used for patents issued alter drug
`approval. Patents issued after drug approval are required to be
`submitted within 30 days of patent issuance for the patent to be
`considered "timely filed."
`
`IOnly information fi'orn form 3542 will be used for Orange
`Book Publication purposes.
`I Forms should be submitted as described in 2i CFR 314.51 An
`additional copy of form 3542 to the Orange Book Staff will
`expedite patent publication in the Orange Book. The Orange
`Book Staff address (as of July 2003) is: Orange Book Staff,
`Office of Generic Drugs OGDJHFD-Glo, 7500 Standish Place,
`Rockville, MD 20855.
`
`- The receipt date is the date that the patent information is date
`stamped in the central document room. Patents are considered
`listed on the date received.
`
`0 Additional copies of these forms may be downloaded from the
`Internet at: httQJI/{arm1 Ere. gav/(onns/‘pja‘ahtm/[dahtmhrm l.
`First Section
`
`Complete all items in this section.
`I. General Section
`
`Complete all
`itself.
`
`items in this section with reference to the patent
`
`Ic)
`
`Include patent expiration date, including any Hatch-Waxman
`patent extension already granted. Do not
`include any
`applicable pediatric exclusivity. The agency will
`include
`pediatric cxclusivitics where applicable upon publication.
`
`id)
`
`Include full address of patent owner. If patent owner resides
`outside the U. S. indicate the country in the zip code block.
`
`le)
`
`Answer this question ifapplicable. If patent owner and NBA
`applicantt'holder reside in the United States,
`leave space
`blank
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section if the patent claims the drug
`substance that is the subject of the pending NDA, amendment, or
`supplement.
`
`2.4) Name the polymorphic form of the drug identified by the
`patent.
`
`2.5) A patent for a metabolite of the approved active ingredient
`may not be submitted. If the patent claims an approved
`method of using the approved drug product to administer
`the metabolite the patent may be submitted as a method of
`use patent depending on the responses to section 4 of this
`form.
`
`2.7) AnSWer this question only if the patent
`process patent
`
`is a product-by-
`
`3. Drug Product (Composition/Formulation)
`
`items in this section it‘ the patent claims the drug
`Complete all
`product that is the subject of the pending NDA, amendment1 or
`supplement.
`
`3.3) An answer to this question is required only if the referenced
`patent is a product-by—pmoess patent.
`4. Method of Use
`
`Complete all items in this section if the patent claims a method of
`use of the drug product that is the subject of the pending NDA,
`amendment. or Supplement.
`
`42)
`
`identity by number each claim in the patent that claims the
`use(s) of the drug for which approval
`is being sought.
`Indicate whether or not each individual claim is a claim for
`a. method(s) of use of the drug for which approval is being
`sought.
`
`4.2a) Specify the part of the proposed drug labeling that
`claimed by the 1:8an
`
`is
`
`5. No Relevant Patents
`
`Complete this section only ifapplicable.
`6. Declaration Certification
`
`Complete all items in this section.
`
`6.2) Authorized signature. Check one of the four boxes that best
`
`FORM FDA 35428 (7103)
`
`Page 6
`rec Mail-Maflfllllll-lm I-‘.F
`
`
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`Actavis - IPR2017-O1101, Ex. 1016, p. 8 of 102
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`

`

`
`
`‘
`
`C
`
`.
`‘
`b. Issue Date of Patent
`111412003
`Address (olPeteni Owner)
`2730 Wilshire Boulevard, Suite 1I0
`
`e. Name gt agent or representative who reside: or maintains
`a place at business within the United States authorized to
`receive notice of patent codification under section
`505MB) and (SIRIUS) of the Federal Food, Drug. and
`GosmeticAct and 21 CFR 314.52 and 314.95 (it patent
`owner or MBA applieantihclder does not reside or have a
`place of business within the United States)
`<7” Nr'A
`
`Cityi'State
`Santa Monica, CA
`ZIP Code
`90403
`
`Telephone Number
`310 883 1300
`
`FAX Numgor (ifavaiiablo)
`3!!) 993 3553
`
`EMaitAddress (if available)
`
`Address (of agent or representative named in 1.9.)
`
`Cit-yiState
`
`ZiP Code
`
`Telephone Number
`
`FAX Number {if available)
`
`f.
`
`Is the patent reterenced above a patent that has been submitted previously for the
`approved NDA or supplement referenced above?
`9. lithe patent referenced above has been submitted previously for listingI is the expiration
`date a new expiration date?
`
`FORM FDA 3542a (7103}
`
`I] Yes
`
`END
`
`D Yes
`
`DNo
`
`Page 1
`rs: Mun- AnatnleI-IW EF
`
`16
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 9 of 102
`
`American BioScience, Inc.
`
`N21660
`
`Department of Health and Human Services
`Food and Drug Administration
`
`PATENT INFORMATION SUBMITTED WITH THE
`FILING OF AN NDA, AMENDMENT, OR SUPPLEMENT
`For Each Patent That Claims a Drug Substance
`(Active ingredient), Drug Product (Formulation and
`Composition) and/or Method of Use
`
`Form Approved: OMB No. 0910-0513
`Expiration Date: 07i31l06
`See OMB Stetementon Page 3.
`NBA NUMBER
`21-660
`NAME OF APPLICANT! NDA HOLDER
`American BioScieuce, Inc.
`
`The following is provided in accordance with Section 505(k) and (c) of the Federal Food. Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`Abraxanem (nob Paclitaxel) for Injectable Suspension
`ACTIVE INGREDtENTtS)
`Pacl itaxel
`
`STRENGTHtS)
`I00 rug/vial
`
`DOSAGE FORM
`Sterile powder for injectable suspension
`
`required to be submitted to the Food and Drug Administration (FDA) with an NBA application,
`This patent declaration form is
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53tdll4).
`Within thirty (30) days after approval at an MBA or supplement, or within thirty (30) days of issuance of a new patent. a new patent
`declaration must be submitted pursuant
`to 21 CFR 314.53(c)(2)(ii) with all of the required information based on the approved NDA
`or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA ior listing a patent in the Orange Book.
`
`For handwritten or typewriter verelons (only) of this report: If additional space is required for any narrative answer (in, one
`that does not require a “Yes” or "No' response). please attach an additional page relerencing the question number.
`
`FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the
`patent is not eligible for listing.
`_____——_________———.—.——-—
`For each patent submitted for the pending NBA. amendment, or supplement referenced above. you must submit all the
`information described below. if you are not submitting any patents for this pending NDA, amendment. or supplement.
`lete above section and sections 5 and 6.
`1.6ENERAL
`a. United States Patent Number
`6,506,405
`d. Name at Patent Owner
`American BioScience, Inc.
`
`-
`c. Explraticn Date
`2.923013
`
`Patient
`
`'
`
`-
`
`Actavis - IPR2017-01101, Ex. 1016, p. 9 of 102
`
`

`

`
`
`American BioScience, inc.
`
`N21660
`
`For the patent referenced above. provide the following information on the drug substance. drug product and/or method of
`use (trails the subject of the pending NBA. amendment. orsuppiement.
`
`
`
`is the actiue ingredient in
`2.1 Does the’petenl claim the drug substance
`described in the pending NDA. amendment, or supplement?
`2.: Does the patent claim a drug substance that is a dirterent potymerph otthe active
`ingredient described in the pending NDA. amendment. or supplement?
`2.3 If the answer to question 2.2 is 'Yes,‘ do you certify that. as of the date of this declaration, you have test data
`demonstrating that a drug product containing the poiymorph will perform the same as the drug product
`described in the NBA? The type of test data required is described at 21 CFR 314.53(b).
`2.4 Specify the polymorphic fOH‘I'I(S) claimed by the patent for which you have the test results described in 2.3.
`
`2.5 Does the patent claim onty a metabolite of the active ingredient pending in the NDA or supplement?
`(Complete the intonhation in section 4 below if the patent claims a pending method of using the pending
`drug product to administer the metabolite.)
`2.6 Does the patent claim only an intermediate?
`
`UYes
`
`2.? lithe patent referenced in 2.1 is a product-by-prooess patent, is the product claimed in the
`patent novel? (An answer is required only it the patent is a product-by—process patent.)
`7p
`-_r.3:~,.‘
`:
`.
`_
`_
`3. DrugrProdtSctlCotttpoertloru’Fot-n'lulnflon)
`3.1 Does the patent claim the drug produd. as defined in 21 CFR 314.3, in the pending NDA.
`amendment. or supplement?
`3.! Does the patent claim only an intermediate?
`
`3.3 It the patent referenced in 3.1 is a product-by—process patent. is the product claimed in the
`patent novel? (An answer is required only if the patent is a pmdud-by-pmoess patent.)
`
`4. ‘Method- or Use
`
`-
`
`r
`
`Sponsors must submit the information in section 4 separately for each patent claim claiming a method of using the pending drug
`product for which approval is being sought. For each method of use claim referenced. provide the following information:
`4.1 Does the patent claim one or more methods of use lot which approval is being sought in
`the pending NDA, amendment. or supplement?
`
`Dita
`
`
`
`4.2 Patent Claim Number (as listed in the patent)
`13—22, 24-34, 36—40, 44, 46, 4B, 52, 54. 56,
`58, 60
`
`E Yes
`Does the patent claim referenced in 16.2 claim a pending method
`of use for which approval is being sought in the pending NDA.
`Yes
`amendment. or supplement?
`
`EINe
`
`FORM FDA 35423 (TIM)
`
`Page 2
`)SCMAi-MIIHDIHfl-IWD EF
`
`
`
`
`
`Actavis - IPR2017-O1101, Ex. 1016, p. 10 of 102
`
`17
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`
`
`Actavis - IPR2017-01101, Ex. 1016, p. 10 of 102
`
`

`

`American BioScience, Inc.
`
`N21660
`
`
`
`
`
`4.2: if the answer to 4.2 is
`'Yes.‘ identity with speci—
`My the “39 With "3""-
`once to the proposed
`Iaboihv forlhe druv
`Product
`
`
`
`Use: (Submit moon ormethodofuse intervention as identified WWI?! b‘ro approved floating.)
`Claim! 13-22. 2446. 33-34. 35. 37-40. 44. 46. 4B. 54. and 55 -Abraxane (nab positional) for iniectable suspension is a
`nanopanicie Iibumin-bound (nab) form of paciiimt. See Description. Each smote-use vial contains 100 mg of
`padnaxet and approximately 900 mg of human albumin. See Dasa'fption. Thh formulation is free from solvents. See
`Description. Abraxane (nab paclitaxel) for injectable suspension is lndimted fertile treatment utmost
`cancer. See intimation. Abmrcane does not contain Cremophor-EL. therefore hypersensitivity reactions to Abmane
`were rare. See Adverse Reactions: Hypersensitiva Reactions (HSRs). For metastatic breast cancer. Annmarie (neb-
`psclitaxei for injectabie suspension) at a dose of 260 moim‘ administered intravenously over 30 minutes every 3 weeks
`has been shown to be effective. Sea Dosage and Administration. No premedication is required prior to the
`administration at Abmxane. See Dosage and Administration: Preparation and Administration Precautions.
`
`
`
`
`
`
`
`
`
`
`
`Claims 27-29 - Abrsxane (nab paclitaxel) for injectabfe suspension is a nanoparticle albumin~bound (nab) form of
`pactitaxel. See Description. Each single-use via] contains 100 mg of paciitaxet and approximately 900 mg of human
`albumin. See Description. This formulation has from solvents. See Description. Aerator-re (nab paclitarrel tor
`
`lniectable suspension) is indicated for the treatment of” breast corner. See indication. Abraxane does not
`
`
`contain Cremophor-EL. theretore hypersensitivity reactions to Abraxane were rare. See Adirerse Reactions:
`
`
`Hypersensitivity Reactions 9-15st. Nettropenla. the most important hematologic toxicity. was dose dependent and
`
`
`was generally rapidly reversible. See Adverse Reactions: Hemetotogic. Grade 4 ((500 oeltefmm’) neutropanie
`
`
`occurred in 12% of patients treated with Abtaxane. See Adverse Reactions: Hematologic. Among patients treated in
`
`
`the Phase 3 metastatic breast cancer study. neutmphll counts declined below 500 cellsimrn' (Grade 4|) in 9% of the
`
`
`patients treated with a dose of 260 mgim1 compared to 22% in patients receiving Cremephcr-based paclitaxel iniection
`
`
`at a dose of 175 mgi‘m‘. See Adwrsa Reaciims: Hematologic. For metastatic breast cancer. Abram-me (nab
`
`
`pactitaml for inledable suspension) at a dos of 260 mgim' administered intravenously over 30 minutes every 3 weeks
`
`
`has been shown to be effective. See Dosage and Administration.
`
`
`Claims 30-32 - Abruane (nab pact‘rtanei) for iniectahio suspension is a nenoparticle albumin-bound (nap) form of
`pactitaxel. See Description. Each single-use vial contains 100 mg of paclitaxei and approximately 900 mg of human
`albumin. See Description. This formutalion is tree from solvents. See Description. Abraxane (nab pactaaxel) for
`injectable suspension Is indicated for the treatment omen cancer. See indication.
`In general. the
`
`frequency and severity of neurologic meniftastations were dose-dependent in patients receiving single-agent Abraxane.
`
`See Adverse Reactions: Neoroiogic. Peripheral neuropathy was observed in 64% of all patients (10% severe). See
`
`Adverse Reactions: Neuroiogrc. Peripheral neuropathy was the cause at Abraxane discontinuation in 131366 {4%) of
`
`all patients. See Adverse Reactions: Neurologic. Sensory symptoms have usually inproved or resolved within 22
`days of interrupting AbraJrane therapy. See Adverse Reactions: Neuroiogic. Pro-existing neuropathles resulting from
`
`prior therapies are not a contraindication for Abraxane therapy. See Adverse Re