I 1111111111111111 1111111111 111111111111111 11111 lllll 111111111111111 11111111
`
`US010478453Bl
`
`c12) United States Patent
`Maloney et al.
`
`(10) Patent No.: US 10,478,453 Bl
`(45) Date of Patent:
`Nov. 19, 2019
`
`(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)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`(21) Appl. No.: 16/248,460
`
`(22) Filed:
`
`Jan. 15, 2019
`
`(51)
`
`(52)
`
`Int. Cl.
`A61K 9/00
`A61K 33/06
`A61K 31/191
`A61K 47102
`A61K 33/36
`A61K 331241
`A61K 33/28
`A61K 33/00
`A61K 311405
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2019.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(Continued)
`
`U.S. Cl.
`CPC .............. 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 311401 (2013.01); A61K
`311405 (2013.01); A61K 3114172 (2013.01);
`A61K 33/00 (2013.01); A61K 331241
`(2019.01); A61K 33/28 (2013.01); A61K 33/36
`
`(2013.01); A61K 47102 (2013.01); A23V
`2002/00 (2013.01); A61J 1/1412 (2013.01)
`(58) Field of Classification Search
`CPC ..... A61K 9/0029; A61K 31/095; A61K 47/02
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`6,992,218 B2
`7,323,206 Bl
`9,220,700 B2
`
`1/2006 Dietlin et al.
`1/2008 Driscoll et al.
`12/2015 Savarese et al.
`
`OTHER PUBLICATIONS
`
`Jalilehvand et al (Inorg. Chem., 2015, 54 (5), pp. 2160-2170). (Year:
`2015).*
`
`(Continued)
`
`Primary Examiner - Benjamin J Packard
`(74) Attorney, Agent, or Firm -Alston & Bird LLP
`
`ABSTRACT
`(57)
`The subject matter described herein is directed 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 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 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) to about 1 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.
`
`22 Claims, 5 Drawing Sheets
`
`-------------------------------------------------------------------------------------------------------------------------------------------------------------·
`
`Dissolved Oxygen Levels per Tray
`
`14.0
`
`12.0
`
`10.0
`
`C!!.O
`0
`
`4.0
`
`2.0
`
`0.0
`
`Final Dissolved Oxygen Post Filling -Pre HSR
`
`Post Filling - During
`
`~Trayl [
`~Tr,iy 2 :
`~-.-.»-.-.-.Tr;,y 3 [
`~Tray4 [
`~Tray 17:
`w.%._._._ Tray 18[
`~ .... ~ ... fray19:
`-Tray20[
`•.•.•.•.•.•.•.•. fray 21[
`~Tray 22:
`•.•.• ;;:;-•.•.• Tray 23 [
`
`·.:::::::;:::::. ~~:; ~~ ~
`
`········•:•.····Tray 38 [
`•·•·····:•,·,·,·Tray 39;
`•···•·.:.·•···•T;ay40[
`I
`Post HSR -Capping•
`
`·················C·o·~·p~~~~i~~ ................................................. L~a.d.in.g.~f.~y~················ Filled Vials ................ 1
`
`Nexus Ex. 1019
`Page 1 of 43
`
`

`

`US 10,478,453 Bl
`Page 2
`
`(51)
`
`Int. Cl.
`A61K 311401
`A61K 3114172
`A23L 331175
`A23L 33/16
`A61K 31/198
`A61K 31/095
`A61J 1/14
`
`(2006.01)
`(2006.01)
`(2016.01)
`(2016.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`(56)
`
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`Nexus Ex. 1019
`Page 2 of 43
`
`

`

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`Page 3
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`Nexus Ex. 1019
`Page 3 of 43
`
`

`

`US 10,478,453 Bl
`Page 4
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`
`

`

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