( 12 ) United States Patent
`Maloney et al .
`
`( 10 ) Patent No .: US 10,583,155 B1
`( 45 ) Date of Patent :
`* Mar . 10 , 2020
`
`USO10583155B1
`
`( * ) Notice :
`
`( 54 ) STABLE , HIGHLY PURE L - CYSTEINE
`COMPOSITIONS FOR INJECTION AND
`METHODS OF USE
`( 71 ) Applicant : Exela Pharma Sciences , LLC , Lenoir ,
`NC ( US )
`( 72 ) Inventors : John Maloney , Salisbury , NC ( US ) ;
`Aruna Koganti , Lenoir , NC ( US ) ;
`Phanesh Koneru , Waxhaw , NC ( US )
`( 73 ) Assignee : Exela Pharma Sciences , LLC , Lenoir ,
`NC ( US )
`Subject to any disclaimer , the term of this
`patent is extended or adjusted under 35
`U.S.C. 154 ( b ) by 0 days .
`This patent is subject to a terminal dis
`claimer .
`( 21 ) Appl . No .: 16 / 665,702
`( 22 )
`Filed :
`Oct. 28 , 2019
`Related U.S. Application Data
`( 63 ) Continuation of application No. 16 / 248,460 , filed on
`Jan. 15 , 2019 , now Pat . No. 10,478,453 .
`( 51 ) Int . CI .
`A61K 33/06
`A61K 33/241
`
`( 52 ) U.S. CI .
`CPC
`
`( 2006.01 )
`( 2019.01 )
`( Continued )
`A61K 33/06 ( 2013.01 ) ; A23L 33/16
`( 2016.08 ) ; A23L 33/175 ( 2016.08 ) ; A61K
`9/0029 ( 2013.01 ) ; A61K 31/095 ( 2013.01 ) ;
`A61K 31/191 ( 2013.01 ) ; A61K 31/198
`( 2013.01 ) ; A61K 31/401 ( 2013.01 ) ; A61K
`31/405 ( 2013.01 ) ; A61K 31/4172 ( 2013.01 ) ;
`( Continued )
`
`( 58 )
`
`( 56 )
`
`Field of Classification Search
`CPC
`A61K 9/0029 ; A61K 31/095 ; A61K 47/02
`See application file for complete search history .
`References Cited
`U.S. PATENT DOCUMENTS
`6,992,218 B2
`1/2006 Dietlin et al .
`7,323,206 B1
`1/2008 Driscoll et al .
`( Continued )
`
`OTHER PUBLICATIONS
`Sigma - Aldrich production information for L - cysteine hydrochloride
`monohydrate ( May 2006 ) . ( Year : 2006 ) . *
`( Continued )
`Primary Examiner — Benjamin J Packard
`( 74 ) Attorney , Agent , or Firm
`Alston & Bird , LLP
`( 57 )
`ABSTRACT
`The subject matter described herein is directed to stable
`L - cysteine compositions for injection , comprising : L - cyste
`ine or a pharmaceutically acceptable salt thereof and / or
`hydrate thereof in an amount from about 10 mg / mL to about
`100 mg / mL ; Aluminum in an amount from about 1.0 parts
`per billion ( ppb ) to about 250 ppb ; cystine in an amount
`from about 0.01 wt % to about 2 wt % relative to L - cysteine ;
`pyruvic acid in an amount from about 0.01 wt % to about 2
`wt % relative to L - cysteine ; a pharmaceutically acceptable
`carrier , comprising water ; headspace O , that is less than
`1.0 % ; dissolved oxygen present in the carrier in an amount
`from about 0.01 parts per million ( ppm ) to about 1 ppm ,
`wherein the composition is enclosed in a single - use con
`tainer having a volume of from 10 mL to 100 mL . Also
`described are compositions for a total parenteral nutrition
`regimen and methods for their use .
`30 Claims , 5 Drawing Sheets
`
`14.0
`
`12.0
`
`10.0
`
`DO ( ppm ) 8.0
`
`6.0
`
`4.0
`
`2.0
`
`0.0
`
`Dissolved Oxygen Levels per Tray
`
`Tray 1
`Tray 2
`Tray 3
`My Tray 4
`wwwxTray 17
`Tray 18
`AWARAW Tray 19
`Tray 20
`wwwTray 21
`ya Tray 22
`Tray 23
`ww Tray 24
`shox Tray 37
`Tray 38
`Tray 39
`** Tray 40
`
`Post Filling -Pre HSR
`Final Dissolved
`Oxygen Compounding
`
`Post Filling - During
`Loading of Lyo
`
`Post HSR -Capping -
`Filled Vials
`
`Nexus Ex. 1015
`Page 1 of 42
`
`

`

`US 10,583,155 B1
`Page 2
`
`( 2006.01 )
`( 2016.01 )
`( 2016.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`( 2006.01 )
`
`( 51 ) Int . Ci .
`A61K 31/401
`A23L 33/16
`A23L 33/175
`A61K 31/405
`A61K 31/095
`A61K 9/00
`A61K 33/00
`A61K 47/02
`A61K 31/191
`A61K 31/198
`A6IK 31/4172
`A61K 33/36
`A61K 33/28
`A61 ) 1/14
`( 52 ) U.S. CI .
`A61K 33/00 ( 2013.01 ) ; A61K 33/241
`???
`( 2019.01 ) ; A61K 33/28 ( 2013.01 ) ; A61K 33/36
`( 2013.01 ) ; A61K 47/02 ( 2013.01 ) ; A23V
`2002/00 ( 2013.01 ) ; A61J 1/1412 ( 2013.01 )
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`
`Nexus Ex. 1015
`Page 2 of 42
`
`

`

`US 10,583,155 B1
`Page 3
`
`( 56 )
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`
`Nexus Ex. 1015
`Page 3 of 42
`
`

`

`US 10,583,155 B1
`Page 4
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`
`Nexus Ex. 1015
`Page 4 of 42
`
`

`

`US 10,583,155 B1
`Page 5
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`( 56 )
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