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`USOU92542?8B2
`
`(12)
`
`United States Patent
`Seharschmidt et :1].
`
`(10) Patent No.:
`(45; Date of Patent:
`
`US 9,254,278 B2
`*Feb. 9, 2016
`
`(54)
`
`(71)
`
`(72)
`
`METHODS OF THERAPEU'l'IC
`MONITORING OF NITROGEN SCAVENGING
`DRUGS
`
`Applicant: Horizon Therapeutics, Inc.. Deerfield.
`II. (US)
`
`Inventors: Bruce Scharschmidt, San Francisco.
`(TA (US): Masuud Mokhtaraui. Walnul
`(‘re-cl\'. (‘A (US)
`
`(73)
`
`Assignees
`
`Horizon Therapeutics, Inc:.. Deerfield.
`1 1.. ( U S)
`
`(*)
`
`Notice:
`
`Subjecl to any disclaimer. lhe term oflhis
`patent is extended or adjusled under 35
`U.S.C. 15403) by 0 days.
`
`This palent is subjec:1 lo a lerminal dis-
`claimer.
`
`(21)
`
`Appl. No; 14.-816,674
`
`(22)
`
`Filed:
`
`Aug. 3, 2015
`
`(65)
`
`(63)
`
`(60)
`
`(51)
`
`Prior Publication Data
`
`US 2015110335605 Al
`
`Nov. 26. 2015
`
`Related U.S.Applieation Data
`
`Continuation of application No. l3f775,000, filed on
`Feb. 22. 2013. now Pen. No. 9.095.559. which is a
`coxilixinaiinn oliapplicatioll No. l3f4l7.137. filed on
`Mar. 9. 2012. now Pat. No. 8.404.215.
`
`Provisioiizil application No. GUS-12_.l(l0. filed on Sep.
`30. 2011. prm'isiLn1eIl application No. 611564.668.
`filed on Nov. 2.9. 2011.
`
`Int. Cl.
`/l6IK 49/00
`/[6IP I3/00
`
`(2006.01)
`(20(}6.{)l )
`[(.'o11Iin1II.'d)
`
`(52)
`
`U.S. Cl.
`CPC
`
`33/4925 (2013.01): GUIN 2800/085 (2013.01):
`Y!0T436/175383 (2015.01)
`(58) Field of Classification Search
`(‘PC
`A61K 3111216: GOIN 311221: YIOT
`4361125383
`......... .. 42419.2: 5141432. 433. 544. 570. 533:
`436M. 113
`
`USPC‘
`
`Sec appliczllion lilo for complete SCE|l'Cl1 history.
`
`(56)
`
`References Cited
`
`U .S. PATENT DOCUMENTS
`
`4.284.fi4? A
`4.457.942 A
`
`8.-"I981 Bnisilowetal.
`7.-' I984 Brusilow
`
`[(‘on1iI1ued}
`
`FOREIGN PATENT DOCUMENTS
`
`W0
`W0
`
`W094.-"22494
`\\’()2{}0S.-"(]5360?
`
`I0-" I 994
`6-2005
`
`(('onIinued}
`
`OTHER PUBLICATIONS
`
`Amodio. P.. el 3].. “Deleclinn of Minimal Hepalit: Encephalopaihyz
`Norinzilizaiion and {')pli1ni?a.lion of [he Psychomelrlc Hepalic
`Encephalopzithy Score. A Neumpsychological and Quantified IZEG
`Sludy.” J. llcpatol. 49346-3 53 (2(JU'S).
`[(‘nnlinuod)
`
`I’r.5)i.=a'!'_i-' }:L\'ami'r.-er
`
`Savilha Rao
`
`(5?)
`
`ABSTRA(?'l‘
`
`The present disclosure provides methods for evaluating daily
`zn'nn1onia exposure based on a single fasting. annnonia blood
`level measllremenl. as well as uletlmds lhal u1i1i';.c Lhis tech-
`nique to adjusl the dosage of a 1'1iLl'0gCl‘l scavengi11_g drug.
`determine whether to administer a nitrogen scavenging drug.
`and treat nitrogen retention disorders.
`
`A6IK3I/216 (2013.01): /161K 9/9053
`(201301 ):_ (MIN 31/221‘ (2013.01): GQIN
`
`15 Claims, 3 Drawing Sheets
`
`Emmi»
`
`NH.‘
`u.-Ktmglana-me
`
`-—lL-ifllinalim \.p('s|T\-P-'I=-t 73l'»fl§‘i4‘¢“|l 1-1'IIm\«l'nurylI'.e
`GI It 15 —;-NH‘,I
`
`ills]-an-amt
`
`""~°s"“\¢/""1"
`11*-3
`i
`canm.-_.1 phosvluihr
`
`OTC
`
`[3':,5..~"‘:T,.....""':::
`"
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`Urinernaaloli
`9 ‘.
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`
`1 of 22
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`1 of 22
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`

`

`US 9,254,278 B2
`Page 2
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`(51)
`
`Int. (31.
`A6IK 31/216
`A6IK 9.490
`GQIN 31/22
`(;arN 33/49
`
`(2006.01)
`(2006.01)
`(2006.01)
`(200601 )
`
`(56)
`
`References Cited
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`U.S. PATENT DOCUMENTS
`
`5.654.333 A
`5.968.979 A
`6.060.510 A
`6.033.934 A
`6.219.567 131
`8.094.521 B2
`8.404.215 B1
`8.642.012 B2
`9.078.865 B2
`2003.-"0195255 Al
`2U04»"0229948 A1
`200570273359 Al
`200630135612 Al
`2008.-"0119554 A1
`2010.-'000885‘) A1
`20l0.»'00l(t207 Al
`201270022157 Al
`20l2»’0220661 A1
`2013.-"02109l4 A1
`2013.-"0281530 Al
`2014.-"0142186 Al
`201570094278 Al
`201530105469 A1
`
`831997 Saniid
`10.-‘I999 Brusilow
`532000 Brusilow
`7.52000 Brusilow
`4t'200l Eggers
`1.-'2012 Levy
`352013 Scharsclunidtetal.
`2.-‘"2014 Scharschmidt
`7.'2015 Lee
`l0."2003 Sumrrtar
`11-‘Z004 Summaretal.
`12-""2005 Young
`652006 Ferranle
`S.-‘"2008
`Jalan
`1."2010 Scharschmidt
`172010 Wurtmanctal.
`132012 Scitarschmidt
`8-‘"2012 Lee
`8«'2013 Scharschmidt
`10.-'2013 Scharschmidt et al.
`5.’2014 Scharschmidtetal.
`432015 Scharsclnnidtetal.
`4.520 15 Scharschmidt et al.
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`WO
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`WO200 77005633
`WO2009.r'0 87474
`WO2009.t'134460
`WO2010.i025303
`WO2012.-"028620
`WO2013:'048558
`WO2013-"l58l45
`
`652006
`I 52007
`732009
`1 1320051
`3-"2010
`392012
`4-F2013
`10"2013
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