`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`21-660
`
`ADMINISTRATIVE DOCUMENTS
`
`Actavis - IPR2017-01100, Ex. 1016, p. 1 of 102
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`Actavis - IPR2017-01100, Ex. 1016, p. 1 of 102
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`American BioScience,Inc.
`
`American BioScience, Ine.
`
`Patent Certification
`
`Paragraph II Certification
`
`in the opinion and tu the best knowledge of American BioScience,Inc., there are no
`unexpired patents trat claim the listed drug [Taxo!l® (paclitaxel) Injection] referred to
`
`in this application ur that claim a use of the listed drug.
`
`RQOOK
`
`Mitchall G. Clark
`
`Vice President, i¢cxuiatory Affairs
`
`eles
`
`Date
`
`2730 Wilshice Biva.,ic 110 Santa Monica, California 90403 Tel: (310) 883-1300 Fax: (310) 998-8553
`
`Actavis - IPR2017-01100, Ex. 1016, p. 2 of 102
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`Actavis - IPR2017-01100, Ex. 1016, p. 2 of 102
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`

`
`
`American BioScience, Inc.
`
`N21660
`
`Form Approved: OMB No. 0910-0513.
`Department of Health and Human Services
`Expiration Date: 07/31/06
`Food and Drug Administration
`See OMB Statement on Page 3.
`SANDEE
`PATENT INFORMATION SUBMITTED WITH THE
`FILING OF AN NDA, AMENDMENT,OR SUPPLEMENT|}91-<60
`For Each Patent That Claims a Drug Substance
`NAMEOF APPLICANT / NDA HOLDER
`{Active Ingredient), Drug Product (Formulation and
`American BioScience, Inc.
`Composition) and/or Method of Use
`
`The following is provided in accordance with Section 505(b) and (¢) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME}
`AbraxaneTM (nab Paclitaxel} for Injectable Suspension
`ACTIVE INGREDIENT(S)
`Paclitaxel
`
`STRENGTH(S}
`100 ing/vial
`
`DOSAGE FORM
`Sterile powder for injectable suspension
`
`required to be submitted to the Food and Drug Administration (FOA} with an NDA 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 approval of an NDA 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 forlisting a patent in the Orange Book.
`
`For hand-written or typewriter versions {only} of this report: If additional space is required for any narrative answer (i.e., one
`that does not require a "Yes" or “No” response), please attach an additional page referencing the question number.
`FDA will not list patent information if you file an incompiete patent declaration or the patent declaration indicates the
`patent is not eligible forlisting.
`
`For each patent submitted for the pending NDA, amendment, or supplement referanced above, you must submit ail the
`information described below. if you are not submitting any patents for this pending NDA, amendment, or supplement,
`fete above section and sections & and 6.
`4. GENERAL
`a. United States Patent Number
`6,537,579
`d Name of Patent Owner
`American BioScience, Inc.
`
`"
`
`cate a new expiration date?
`
`a
`”
`
`b. issue Date of Patent
`3/25/2003
`Address (of Patent Owner}
`2730 Wilshire Boulevard, Suite 110
`
`-
`"3
`c. Expiration Date ofPatent
`2/22/2013
`
`City/State
`Santa Monica, CA
`ZIP Code
`90403
`
`Telephone Number
`310 883 1300
`
`FAX Number (ifavailable)
`310 998 8553
`
`E-Mail Address (if available)
`
`e. Name of agent or representative who resides or maintains Address (of agent or representative named in 1.8.)
`a place of business within the United States authorized to
`receive notice of patent certification under section
`505{b)(3} and (j)(2}(B) of the Federal Food, Drug, and
`Cosmelic Act and 24 CFR 314.52 and 314.95(if patent
`owner of NDA applicani/holder doas not raside or have a
`place of business within the United States)
`“ ms
`
`City/State
`
`— ‘~
`
`Telephone Number
`
`E-Mail Addrass (# available)
`
`f.
`
`Is the patent referenced above a patent that has been submitted previously for the
`approved NDA or supplement referencad above?
`q ifthe patent referenced above has been submitted previously forlisting, is the expiration
`
`FORM FDA 3542a (7/03)
`
`Page 7
`PSC Media Arts (301) 443-1090 EF
`
`
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`Actavis - IPR2017-01100, 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 and/or method of
`use that Is the subject ofthepending NDA, amendment, orsupplement.
`2. Sirug Sdbitanc (‘ictive ingrsiler
`2.1 Does the patent claim the drug substance Thal is theaciva ingredient]in the drug product
`described in the pending NDA, amendment, or supplement?
`2.2 Does the patent claim a drug substance that is a differant polymorph of the active
`ingredient described in the pending NDA, amendment, or supplement?
`2.3 Ifthe answerto question 2.2 !s “Yas," do you certify that, as of the date of this declaration, you have test data
`demonstrating that a drug product containing the polymorph will perform the same as the drug product
`described in the NDA7 Thetype of test data required is described at 21 CFR 314.53(b).
`2.4. Specify the polymorphic form(s} claimed by the patent for which you have the test results described in 2.3.
`
`O Yes
`
`2.5 Does the patentclaim onty a metabolite of the active ingredient pending in the NDA or supplemant?
`(Complete the informationin section 4 below if the patent claims a pending method of using the pending
`drug product to administer tha metabolite.}
`2.6 Does ihe patent claim onty an intermediate?
`
`oO Yes
`
`& No
`
`2.7 Ifthe patent referenced in 2.4 is a product-by-process patent, is the product claimed in tha
`patent novel? (An answeris required only if the patent is a product-by-procass pateni.)
`3.-Diug Product{Coinpesition/Fentiulation)
`3.1 Does the patentclaim the drug product, 2s defined in 21 CFR 314.3,in the panding NDA,
`amendment, or supplement?
`3.2 Does the patentclaim onty an Intermediate?
`
`3.3
`
`Ifthe patent referenced in 3.4 is a product-by-processpatent, is the product claimed in the
`patent novel? (An answeris required only if the patentis 8 product-by-process patent)
`
`Oo No
`
`4. Mathod of Use
`Sponsors must submit the information in section 4 separately for each patent claim <iaining @ method of using the pending ‘Greg
`productfor which approvalis belng sought For each method of use claim referenced, provide the following information:
`4.4 Does the patent claim one of more methods of use for which approvalis being saught In
`the pending NDA, amendment, or supplement?
`4.2 Patent Claim Number(asfistad in the patent)
`L-6, 10-15, 22-27, 30-42, 49-51
`
`oJ Yas
`Does the patent claim referenced in 4.2 claim a pending method
`of use for which approval is being sought in the pending NDA,
`amendment, or supplement?
`ne Yes
`
`OO No
`
`Page 2
`FORM FDA 3542a (7/03}
`FSC Media Aol) 400«=EF
`
`
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`Actavis - IPR2017-01100, Ex. 1016, p. 4 of 102
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`

`

`American BioScience, [nc.
`
`N21660
`
`4.22 ifthe answerto 4.2 is
`Use: (Submit indication ormethod of use information as identified specifically in the approved labeling.)
`“Yas,” identity with speci-
`Claims 10-15 - Abraxane {nab paclitaxel) for injectable suspension is a nanoparticle albumin-bound (rab) form of
`ficity the use with refes-
`paclitaxel. Sea Description, Each single-use vial contains 100 mg of paciitaxel and approxdmatety 900 mg of human
`ence to the proposed
`albumin. Sea Description. This formulation is fee from solvents, See Description. Abraxane (nab pactitexel) far
`labeling for the drug
`injectable suspension Is Indicated for the treatment of‘AERro251 cancer. See indication. Abraxane does not
`product.
`contain Cremopher-EL, therefore hypersensitivity reactionstoAbraxane are rare. Sea Adverse Reactions:
`Hypersensitivity Reactions (HSAs). For metastatic breast cancer, Abraxane (nab pactitaxel for injectable suspension}
`at a dose of 260 mg/m’ administered intravenously over 30 minutes every 3 weeks has been shown to be affective.
`See Dosage and Administration.
`
`Claims 22-27, 32-34, 39-42, and 49-51 - Abraxane (nab pactitaxal) for injectable suspension is a nanoparticle atbumin-
`bound (nab) form of paclitaxel. See Descriptian. Abraxane is supplied a3 a white to yellow, sterile, lyophilized powder
`intended for reconstitution with 0.9% Sodium Chioride Injection, USP pricr to intravanaua infusion. Sed Description.
`Each single-use vial contains 100 mg of paclitaxel and approximately 900 mg of human albumin. See Description.
`Abraxane (nab paclitaxel} for injectable suspension is indicated for the treatment of gM breasi cancer. See
`indication. For metastatic breast cancer, Abraxane (rab paclitaxel!for injectable suspension} al a dose of 260 mgim?
`administered intravenously over 36 minules every 3 weeks has been shown to be effective. See Dosage and
`Administration, Abraxana is supplied as a sterile lyophilized powder for reconstitution before use, See Dosage ard
`Administration: Preparation for intravenous Administration, Reconstitute each vial by mjecting 20 mL of 0.9% Sodium
`Chloride Injection, USP. See Dosage and Administration: Preparation for intravenous Administration. Each mL of the
`reconstituted nanoparticte formulation will contain 5 mg/mL paclitaxel. See Dosage and Administration: Preparation for
`latravenous Administration.
`
`Chloride Injection, USP. See Dosage and Administration: Preparation for intravenous Administration,
`
`Claim 30 - Abraxane (nab paclitaxel) for injectable suspension is a nanoparticle albumin-bound (nad) fonm of paclitaxel.
`See Description. Each single-use vial contains 190 mg of pactitaxel and approximately 900 mg of human albumin.
`See Description. This formutation is frae from solvents. See Description. Abraxane (nab paclitaxel} for injectable
`suspensionIs indicated for the treatment ofquaggiallPbreast cancer. Sea indication. Neutropenia, the most important
`hematologic toxicity, was dosa dependent and was generally rapidly reversible. Soe Adverse Reactions: Hamatafogic.
`Grade 4 (<500 calls/mm’) neutropenia occurred in 12% of patients treated wilh Abraxane, See Adverse Reactions:
`Hematologic. Among patients treated Inthe Phase 3 metastatic breast cancer study, neutrophil counts declined balow
`500 cells/mm’ (Grade 4) in 9% of the palients traaied with a dose af 260 mg/m” compared to 22% in patients receiving
`Cremophor-based paclitaxelinjection at a dose of 175 mgm’. See Adverse Reactions: Hematologic. Among patients
`Abraxane does not contain Cremophor-EL, therefore hypersensitivity reactions to Abraxane are rare. See Adverse
`Reactions: Hypersensiivity Reactions (HSRs). For metastatic breast cancer, Abraxane (nab paclitaxel for injectable
`suspension) at a dose of 260 mgim? administered intravenously over 30 minutes every 3 weeks has been shown to be
`effective. See Dosage and Administration, Abraxane is supplied as a sterile tyophiized powderfor reconstitution
`before use. See Dosage and Administration: Preparation for Intravenous Administration. Reconstitute each vial by
`intecting 20 mL of 0.9% Sodium Chloride Injection, USP. Sea Dosage and Administration: Preparation for Intravenous
`Administration.
`
`Claim 31 - Abraxana (fab paclitaxel} for injectable suspension}is a nanoparticle albumin-bound (ned) form of
`pacitaxel. See Description. Each single-use vial contains #00 mg of paclitaxel and approximately 900 mg of human
`albumin. See Description. Abraxane (ned paclitaxel) for injectable suspension is indicated for the treatment of
`PREovens! cancer. See Indication,
`in general, the frequency and severity of neurologic manifestations were
`ose-dependentin patiants receiving single-agent Abraxane. See Adverse Reactions: Naurofogic. Peripheral
`neuropathy was observed in 64% of all patients (10% severe). See Adverse Reactions: Neurologic. Peripheral
`neuropathy was the cause of Abraxane discontinuation in 13/366 (4%)of all palients. See Adverse Reactions:
`Neurologic. Sensory symptoms have usually improved or resolved within 22 days of interrupting Abraxane therapy.
`See Adverse Reactions: Neurologic. Pre-existing neuropathies resuting from prior therapies are not a contraindication
`for Abraxane therapy. See Adverse Reactions: Neurologic, No incidences of grade 4 peripheral neuropathias were
`reported in the clinicaltrial. See Adverse Reactions: Neurvogic. Other Ihan peripheral neuropathy, serious neurologic
`events following Abraxane administration have been rare (<1%) and have included ischemic stroke, metabolic
`encephalopathy, confusion, dizziness/ightheadednass, and mood altteration/depression. Sea Adverse Reactions:
`Nourologic. For metastatic breast cancer, Abraxane (nab paclitaxelfor injectable suspension) at a dose of 260 mg/m?
`administerad intravenously over 30 minutes every 3 weeks has been shown to be affective. Sea Dosage and
`Administration. Abraxane is supplied as a sterile lyophilized powderfor reconstitution before use. See Dosages and
`Administration: Preparation for intravenous Administration. Reconstitute each vial by injecting 20 mL of 0.9% Sodium
`
`FORM FDA 3542a (7/03)
`
`Page 3
`PSC Meda Art GOH A4!-1090
`«EF
`
`
`
`Actavis - IPR2017-01100, Ex. 1016, p. 5 of 102
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`24
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`

`

`American BioScience,Inc.
`
`N21660
`
`fray submit this declaration directly to the FDA, A patent owner who Is not the NDA applicant’
`NOTE: Only an NDA applicant/holder
`holderis authorized to sign the deciaration but may not submit it directly to FOA, 21 CFR 344.63{c}(4) and (c}(4).
`
`Check applicable box and provide Information below.
`
`4.24 ifthe anewerto 4.2 is
`Use: (Submit indication or method of use information as identified specifically in the approved labeling.)
`
`
`
`“Yes,” identify with speci-|Claims 36 and 38 - Abraxane (nab paclitaxel) for injectable suspension is a nanoparticle albumin-bound (nab) form of
`
`
`
`ficity the use with refer-|paclitaxel. See Description. Abraxane ls supplied es a white to yellow,sterile, lyophilized powderintended for
`
`
`
`ence to the proposed
`reconstilutian with 0.9% Sodium Chiorde Injection, USP prior to intravenous infusion. See Description. Each singie-
`
`
`
`fabeling for the drug
`usevial contains 100 mg of paciitaxe! and approximately 960 mg of human aloumin. See Daseription.
`
`
`
`product.
`Two studies were conducted in 106 patients previously treated with a maximum of one prior chemotherapeutic
`
`
`cagimen. See Cinical Studies: Breast Carcinoma: Phase 2 open label studies. Abraxane was administered in thease
`
`
`
`two trials a3 a 30 minute infusion af doses of 175 mgfm* or 300 mg/m? without steroid premedication or planned G-
`
`
`CSF support. See Clinical Studies: Braest Carcinoma: Phase 2 open iabal studias. Abraxana (nab paclitaxelfor
`injectable suspension) is indicated for the Weatment of suuleaeg.breast cancer. See indication, For metastatic breast
`
`
`cancer, Abraxane (nab-paciitaxel for injectable suspension) at a dose of 260 mgén’ administered intravenously over 30
`
`
`Minutes every 3 weeks haa been shown to be effective. See Dosage and Administration. Abraxane is supplied as a
`
`
`sterile lyophilized powderfor reconstitution before use. See Dosage and Administration: Preparation for intravenous
`
`
`Administration. Reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP. See Dasage and
`
`
`Administration: Preparation for intravenous Administration. No premedication is required prior to the administration of
`Abraxane. See Dosage and Administration; Preparation and Administration Precautions.
`
`
`§. No Relevant Patents
`
`For this pending NDA, amendment, or supplement, there are no relevant patents that claim {ha drug substance (active ingredient),
`
`
`drug product (formulation of composition) or method(s) of use, for which the applicant is seeking approval and with respect to
`i, Yes
`which a claim of patent infringement could reasonably be asserted if a person not licensed by the ownarof the patent engagedin
`
`the manufacture, use, or sale of the drug product.
`
`
`
`6. DeclarationCertification
`
`6.1 The undersigned declares that this is an accurate and complete submission ofpatent information for the NDA,
`
`amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-
`sensitive patent information is submittedpursuant to 2f CFR 314.53. i attast that | am famillar with 21 CFR 314.53 and
`
`
`this submission complies with the requirements of the regulation. { verify under penalty ofperjury that the foregoing
`is true and correct.
`
`
`Waming: A willfully and knowingly false statementis a criminal offense under 16 U.S.C. 1001.
`Date Signed
`
`6.2 Authorized Signature of NDA Applicant/Holder or Patent Owner (Atfomey, Agent, Representalive or
`
`
`other Aufhorized Official) (Propide Information below}
`
`
`Patrick Soon-Shiong, MDf
`A
`an Bioscience, Inc.
`[3 iblog
`
`
`
`
`
`
`
`
`
`
`
`
`
`EI NDA ApplicantHolder
`
`NDA Applicant's/Holder's Attorney, Agen(Representative) or other
`Authorized Officiat
`
`
`
`C1 Patent Owner
`
`i) Patent Owner's Attorney, Agent (Representative) or Other Authorized
`Official
`
`.
`Name
`American BioScience,Inc.
`Address
`2730 Wilshire Boulevard, Suite 110
`
`City/State
`Santa Monica, CA
`
`ZIP Code
`Telephone Number
`
`
`310 883 1300
`90403
`
`
`
`
`
`
`FAX Number (if avaiable)
`E-Mail Addrass(if avaifable)
`310 998 8553
`
`
`
`
`FORM FDA 3542a (7/03)
`
`Page 4
`PSC Adee Arti (01) 449-1070
`EF
`
`
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`Actavis - IPR2017-01100, Ex. 1016, p. 6 of 102
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`

`American BioScience, inc.
`
`N21660
`
`An agency may not conduct or sponsor, anda person is not required to respondto, a collection of
`
`including the time for reviewing
`The public reporting burden for this collection of information has been cstimated to average 9 hours per response,
`instructions, searching existing data sources, gathering and maintaining the data needed, and compicting and reviewing the collection of information. Sead
`comments regarding this burden estimate or any other aspect ofthis collection ofinformation, including suggestions for reducing this burden to:
`Food and Drag Administration
`CDER (HFD-007)
`5600 Fishers Lane
`Rockville, MD 20857
`
`information unless it displays a currently valid OMB cantral number.
`
`FORM FDA 3542a (7/03}
`
`Page §g
`PSC Media Ans (10) 443-1090
`EF
`
`
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`Actavis - IPR2017-01100, Ex. 1016, p. 7 of 102
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`

`American BioScience, tnc.
`
`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
`*To submit patent
`patent declaration form must be used. Two forms are available
`for patent submissions. The approvaf status of your New Drug
`Application wil! determine which form you should use.
`patent
`eForm 3542a
`should
`be
`used when
`submitting
`information with original NDA submissions, NDA amendments
`and NDA suppicments prior to approval.
`
`supplemental
`*Form 3542 should be used after NDA or
`approval. This form is w 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 21 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.
`
`«Form 3542 is also to be used for patents issued after drug
`approval, Patents issued after drug approval are required to be
`submitted within 30 days of patent issuance for the patent 10 be
`considered "timely filed.”
`
`«Only information from form 3542 will be used for Orange
`Book Publication purposes.
`* Forms should be submitted as described in 21 CFR 314.53. An
`additional copy of form 3542 to the Orange Book Staff will
`expedite patent publication in the Orange Hook. The Orange
`Book Staff address (as of July 2003) is: Orange Book Staff,
`Office of Generic Drugs OGD/HFD-610, 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.
`
`+ Additional copies of these forms may be downloaded from the
`Internet at: Atte:/forms. psc. govjorms/dahimdahtmhil.
`First Section
`
`Complete all items in this section.
`lL. 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 net
`include any
`applicable pediatric exclusivity. The agency will metude
`pediatric exclusivities 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}
`
`Answerthis question if applicable. If patent owner and NDA
`applicanvhoider reside in the United States,
`leave space
`blank.
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section if the patent chaims 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 if the patent claims the drug
`Complete all
`product that is the subject of the pending NDA, amendment, or
`supplement.
`
`3.3) An answer to this question ts required only if the referenced
`patent is a product-by-process patent.
`4. Method of Use
`
`Complete all items in this section if the patent claims a method of
`use of the drug productthat is the subject of the pending NDA,
`amendment, or supplement.
`
`4.2)
`
`Identify 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.
`
`42a) Specify the part of the proposed drug labeling that
`claimed by the patent.
`
`is
`
`§. No Relevant Patents
`
`Complete this section only ifapplicabic.
`6. Declaration Certification
`
`Complete ali items in this section.
`
`6.2) Authorized signature. Check onc of the four boxes that best
`
`FORM FDA 3542a (7/03)
`
`Page 6
`PSC MedArtz(308} 443-1090 EF
`
`
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`Actavis - IPR2017-01100, Ex. 1016, p. 8 of 102
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`

`
`
`American BioScience,Inc.
`
`N21660
`
`Ith and Human Services
`Department of Health a
`man Service:
`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. 0940-0513
`Peoivation Date: O7/a1i06
`$e OMB Statementon Page 3.
`
`21-60
`NAME OF APPLICANT / NDA HOLDER
`American BioScience,Inc.
`
`The following is provided in accordance with Saction 505(b) and ({c) of the Faderal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`Abraxane™(nab Paclitaxel) for Injectable Suspension
`ACTIVE INGREDIENT(S}
`Paclitaxel
`
`STRENGTH(S)}
`100 mg/vial
`
`DOSAGE FORM
`Sterile powderfor injectable suspension
`
`required to be submitted to the Food and Drug Administration (FDA) with an NDA application,
`This patent declaration form is
`amendment, or supplement as required by 21 CFR 314.53 af the address provided in 21 CFR 314.534d)(4).
`Within thirty (30) days after approval of an NOA 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 dectaration form submitted upon or after approval will be the only information relied
`upon by FDA forlisting a patent In the Orange Back.
`
`For hand-written or typewriter versions (only) of this report: If additional space is required for any narrative answer {i.e., one
`that does not require a "Yes" or "No" response}, please attach an additional page referencing the questian number.
`
`FDA will not fist patent information if you file an incomplete patent declaration or the patent declaration indicates the
`patent Is not eligible for listing.pSNeeae
`For each patent submitted for the pending NDA, amendment, or supplemant referenced above, you must submit all the
`information described below. If you are not submitting any patents for this pending NDA, amendment, or supplement,
`fete above section and sections 5 and 6.
`1, GENERAL
`a. United States Patent Number
`6,506,405
`d. Name of Patent Owner
`American BioScience, Inc.
`
`-
`b. issue Date of Patent
`1/14/2003
`Address fofPatent Owner)
`2730 Wilshire Boulevard, Suite 1£0
`
`C] No
`
`my a
`c. Expiration Date of Patent
`2/22/2013
`
`, Name of agent or representative whe resides or maintains
`a place of business within the United States authorized to
`receive notice of patent certification under section
`§05(b)(3} and )(2){B) of the Federal Food, Drug, and
`Cosmetic Act and 21 CFR 314.52 and 314.95(if patent
`owner or NDA applicant/hoider does not reside or have a
`place of business within the United States)
`FP NIA
`
`City/State
`Santa Monica, CA
`ZiP Code
`90403
`
`Telephone Number
`310 883 1300
`
`FAX Number(if available)
`340 998 8553
`
`E-Mail Address (# available)
`
`Address (of agent or representative named in 7.4.)
`
`CityiState
`
`ZIP Code
`
`FAX Number(if availabia}
`
`—
`
`f.
`
`Is the patent referenced above a patent that has been submitted previously for the
`approved NDA or supplement referenced above?
`g. Ifthe patent referenced above has been submitted previously forlisting, is the expiration
`dale a new expiration dale?
`
`4] No
`
`oO Yes
`
`{J Yes
`
`FORM FDA 3542a (7/03)
`
`Page 1
`FSC Media Ans (101)443-1090 EF
`
`Actavis - IPR2017-01100, Ex. 1016, p. 9 of 102
`
`16
`
`Actavis - IPR2017-01100, Ex. 1016, p. 9 of 102
`
`

`

`
`
`
`
`American BioScience, inc.
`
`N21660
`
`For the patent referanced above, provide the following information on the drug substance, drug product and/or method of
`use thatis the subjectofthe pendingNNDA, amendment, orsupplement
`2.Dail Substance{Active
`24 Does thetpatent claim the drag substance thatis tha active ingredientinihedrugie
`described in the pending NDA, amendment, or supplement?
`22 Does the patent claim a drug substance thatis a different polymorph of the active
`ingrediant described in the pending NDA, amendment, or supplement?
`2.3 Ifthe answer to question 2.2 Is "Yes," do you certify that, as of tha date of this declaration, you have test data
`demonstrating that a drug product containing the potymo-ph will perform the same as ihe drug product
`described in the NDA? Tha type of test data required is described af 21 CFR 314.53(b).
`24 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3.
`
`2.5 Does the patent claim onty 4 metabolite of the active ingredient pending in the NDA or supplement?
`(Complete the information in section 4 below if the patant claims a pending method of using the pending
`drug product to administer the melabolite.}
`2.6 Does the patent claim only an intermediate?
`
`(J ves
`
`27 ifthe patent referenced in 2.1 is @ product-by-process patent, is the product claimed in the
`patent novel? (An answer is required only @ the patentis a product-by-process patent.)
`3 brug.Product(Composition/Formiulation}
`3.4 Does the patent claim the drug product, as defined in 21 CFR 314.3,in the pending NDA,
`amendment, or supplement?
`3.2 Does the patent claim only an intermediate?
`
`3.4 Ifthe patent referenced in 3.1 is a product-by-processpatent,is the product claimed in the
`patent novel? (An answeris required only if the patentis a product-by-process patent.)
`
`FORM FDA 3542a (7/03)
`
`Page 2
`FSC Media Are (101) 441-1090
`EF
`
`
`
`
`
`Actavis - IPR2017-01100, Ex. 1016, p. 10 of 102
`
`17
`
`
`
`4. Methodof Use
`Sponsors must submit the information In section 4 separately for each patent claim Gaininga mothod of using the pending drug
`productfor which approval is baing sought. For each mathod of use claim referenced, provide the folowing information:
`4.1 Does the patent claim one or more methods of use for which approval is being soughtin
`the pending NDA, amendment, or supplement?
`4.2. Patent Claim Number(as disted in the patent)
`13-22, 24-34, 36-40, 44, 46, 48, $2, 34, 56,
`58, 60
`
`O No
`
`Eine
`
`&] Yes
`Doesthe patent claim referencedin 4.2 claim a pending method
`of use for which approvalis being soughtin the pending NDA,
`amendment, or supplement?
`ia Yes
`
`
`
`Actavis - IPR2017-01100, Ex. 1016, p. 10 of 102
`
`

`

`American BioScience, Inc.
`
`N21660
`
`
`
`
`4.24 if the answerto 4.2 is
`Use: (Submil indication ormathod of use information as identified specifically in the approved labeling.)
`
`
`"Yas," identify with speci-
`Claims 13-22, 24-26, 33-34, 36, 37-40, 44, 46, 48, 54, and 56 - Abraxane (nab paclitaxel) for injectable suspension is a
`
`ficily the use with refer-|ngnoparticle albumnin-bound (nad) form of paclitaxel. See Description. Each single-use vial containa 100 mg of
`
`
`
`enca to the proposed
`paclitaxel and approximately $00 mg of humen albumin. See Dascription. This formulation is free from solvents. See
`
`
`
`labeting for the drug
`Description. Abraxana (nab paclitaxel) for injectable suspension is Indicated for the treatment of pagumbreast
`
`
`
`product.
`gancer. See indication. Abraxane does not contain Cremophor-EL, therefore hypersensitivity reactions to Abraxane
`
`
`were rare. See Adverse Reactions: Hypersensitivity Reactions (HSRs). For metastatic breast cancer, Abraxane (nab-
`paclitaxel! for injactabla suspension) at a dose of 260 mgim? administered intravenously over 30 minutes every 3 weeks
`
`
`has been shown to be effective. See Dosage and Administration. No premedication Is required prior to the
`administration of Abraxane. See Dosage and Administration: Preperation and Adminisiration Pracauitions.
`
`
`
`Claims 27-29 - Abraxane (nab paclitaxel) for injectable suspension is a nanoparticle albumin-bound (nab) form of
`
`
`paclitaxel. Ses Description. Each single-use vial contains 100 mg of paclitaxel and approximately 900 mg of human
`
`
`albumin. See Description. This formulationisfree from solvents. See Description, Abtaxane (nab paclitaxel for
`injectable suspension)is indicated for the treatment ofgggiagts breast cancer. See indication, Abraxane does not
`
`
`contain Cremophor-EL, therefora hypersensitivity reactions to Abraxane were rare, See Adverse Reactions:
`
`
`Hypersensitivity Reactions {HSRs). Neutropenia, the most important hematologic toxicity, was dose dependent and
`
`
`was generally rapidly reversible. See Adverse Reactions: Hamafologic. Grade 4 (<500 callgfmm’) neutropenia
`
`
`occured in 12% of patients timated with Abraxane. See Adverse Reactions: Hematologic. Among patients treated in
`
`
`the Phase 3 metastatic breast cancer study, neutrophil counts declined below 500 calls/mm? (Grade 4) in 9% of the
`
`
`patients tated with a dose of 260 mg/m? compared to 22% in patients receiving Cremophor-based paclitaxel injection
`
`
`al a dose of 175 mgim?. See Adverse Reactions: Hemafologic. For metastatic breast cancer, Abraxane (rab
`
`
`paclitaxcal for injectable suspension) at a dose of 260 mg/m” administered intravenously over 30 minutes every 3 weeks
`
`
`has been shown to be effactive. Sea Dasage and Administration.
`
`
`Claims 30-32 - Abraxane (nab paciitaxel) for injectable suspension Is a nanoparticle albumin-bound (nab) form of
`
`
`pactitaxel. See Description. Each singla-use vial contains 100 mg of paclitaxel and approximately 900 mg of human
`
`
`albumin. See Description, This formutation is free from solvents. See Description. Abraxane (nab pacttaxel) for
`
`
`injectable suspension(s indicated for the treatment ofPalmatreast cancer. See /ndication.
`In general, the
`
`
`frequency and severity of neurologic manifestations were dose-dependentin patients receiving single-agent Abraxane.
`
`
`Sae Adverse Reactions: Naurologic. Peripheral neuropathy was observed in 64% of aii patients (10% severe). Sea
`
`
`Adverse Reactions: Neurologic. Peripheral neuropathy was the cause of Abraxane discontinuation in 13/366 (456) of
`all patiants. See Adverse Reactions: Neurologic. Sensory symptoms have usually improved or resolved within 22
`
`
`days of interrupting Abraxane therapy. See Adverse Reactions: Neurologic. Pre-existing ne