I 1111111111111111 1111111111 1111111111 111111111111111 111111111111111 11111111
`US010653719B1
`
`(12) United States Patent
`Maloney et al.
`
`(10) Patent No.: US 10,653,719 Bl
`(45) Date of Patent:
`*May 19, 2020
`
`(54) STABLE, HIGHLY PURE L-CYSTEINE
`COMPOSITIONS FOR INJECTION AND
`METHODS OF USE
`
`(58) Field of Classification Search
`CPC ...................................................... A61K 33/06
`See application file for complete search history.
`
`(7 1) Applicant: Exe la 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)
`
`(56)
`
`References C ite d
`
`U.S. PATENT DOCUMENTS
`
`6,05.1,567 A
`6.992,218 B2
`
`4/2000 Abrahamson et al.
`1/2006 Dietlin et al.
`(Continued)
`
`OTHER PVBLlCATIONS
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`171is patent is subject to a 1en11inal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 16n73,563
`
`(22) Filed:
`
`,Jan. 27, 2020
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 16/746,028, filed on
`Jan. 17, 2020, which is a continuation of application
`(Continued)
`
`(51)
`
`Int. Cl.
`A6/K 33106
`A61K 33136
`
`(2006.01 )
`(2006.01)
`(Continued)
`
`(52) U.S. Cl.
`CPC .............. A61K 33/06 (2013.01): A23L 33116
`(2016.08); A23l 331/ 75 (2016.08);
`(Continued)
`
`Sigma-Aldrich product information, L-cysteine hydrochloride
`monohydrate (05/06) (Year: 2006).•
`(Con1inut"CI)
`
`Primary Examiner - Benjamin J Packard
`(74) Attorney, Agent, or Firm - Alston & Bird LLP
`
`ABSTRACT
`(57)
`The subject matter described herein is direc1ed to stable
`L-cysteine compositions for injection, comprising: L-cyste(cid:173)
`ine or a pharmaceutically acceptable salt thereof and/or
`hydrate thereof in an amotml from about IO mg/mL 10 about
`.100 mg/mL; Aluminum in au 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
`w1 % re lative to L-cysteine; a pharmaceutically acceptable
`carrier, comprising water; headspace 0 2 that is less than
`1.0%; dissolved oxygen present in the carrier in an amount
`from about 0.01 parts per million (ppm) 10 about I ppm,
`wherein the composition is enclosed in a single-use con(cid:173)
`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.
`
`27 Claims, 5 Drawing Sheets
`
`Dissolved Oxygen Levels per Tray
`
`14.0
`
`12.0
`
`i 10.0
`le
`! g; 8.0
`, _
`i O
`
`6.0
`
`4.0
`
`z.O
`
`-Travl
`~Tray2
`~·rray3
`.-Tray 4
`-xrray 17
`-
`Tray 18
`
`-rray20
`>««««->Tray21
`-.-.1,av 22 I
`~Trav 231
`w.•w ....... Tray 24
`-
`Tray 37
`......-,,.·Tray 38
`=<»,~ Tray 39
`·-
`Tray40
`
`0.0
`
`·
`
`.................. ,
`.................. •
`I
`I
`Final Dissolved
`Post Filling -Pre HSR Post Filling • During Post HSR -Capping•
`j
`Oxygen Compounding
`Loading of Lyo
`Filled Vials
`J
`t .......................................................................................................................................................................................................................... .
`
`Eton Ex. 1106
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`

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`US 10,653,719 Bl
`Page 2
`
`Related U.S. Application Data
`
`No. J 6/665,702, filed on Oct. 28, 2019, now Pat. No.
`I 0,583, I 55, which is a continuation of application
`No. 16/248.460, filed on Jan. 15, 2019, now Pat. No.
`I 0,478,453.
`
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`(51)
`
`(52)
`
`lnt. Cl.
`A6JK 31/401
`A61K 9/00
`A61K 33/00
`A6JK 47102
`A61K 331241
`A23L 33/16
`A61K 31/198
`A61K 31/095
`A23L 331175
`A61K 3114172
`A61K 33128
`A61K 31/191
`A61K 311405
`A61J 1114
`U.S. C I.
`CPC
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.0J )
`(2019.01)
`(2016.0J)
`(2006.01)
`(2006.0J)
`(2016.0J)
`(2006.01)
`(2006.0J)
`(2006.01)
`(2006.01)
`(2006.01)
`
`A61K 9/0029 (2013.01); A61K 31/095
`(2013.01); A61K 311191 (2013.01); A61K
`31/198 (2013.0J); A6JK 31/401 (2013.0J);
`A61K 31/405 (2013.01); A61K 31/41 72
`(2013.0 1); A61K 33100 (2013.01): A61K
`33/241 (2019.01); A 61K 33128 (2013.01);
`A61K 33/36 (2013.01); A61K 47102 (2013.01);
`A23V 2002/00 (2013.01); A6IJ 1/1412
`(2013.01)
`
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