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`1111111111111111111111111111111111111111111111111111111111111
`US009561197B2
`
`c12) United States Patent
`Scharschmidt et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 9,561,197 B2
`*Feb.7,2017
`
`(75)
`
`(54) METHODS OF THERAPEUTIC
`MONITORING OF PHENYLACETIC ACID
`PRO DRUGS
`Inventors: Bruce Scharschmidt, San Francisco,
`CA (US); Masoud Mokhtarani, Walnut
`Creek, CA (US)
`(73) Assignee: Horizon Therapeutics, LLC, Lake
`Forest, IL (US)
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 649 days.
`
`( *) Notice:
`
`This patent is subject to a tem1inal dis(cid:173)
`claimer.
`(21) Appl. No.: 13/610,580
`
`(22) Filed:
`
`Sep. 11, 2012
`
`(65)
`
`Prior Publication Data
`
`US 2013/0281530 Al
`
`Oct. 24, 2013
`
`Related U.S. Application Data
`
`(60) Provisional application No. 61/636,256, filed on Apr.
`20, 2012.
`
`(51)
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`Int. Cl.
`A61K 311192
`A61K 311216
`A61K 311225
`G01N 33168
`(52) U.S. Cl.
`CPC ........... A61K 311192 (2013.01); A61K 311216
`(2013.01); G01N 3316812 (2013.01)
`(58) Field of Classification Search
`CPC ............................ A61K 31/192; A61K 31/216
`See application file for complete search history.
`
`(56)
`
`References Cited
`
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`
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`4,457,942 A
`5,654,333 A
`5,968,979 A
`6,060,510 A
`6,083,984 A
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`8,094,521 B2
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`2/2014 Scharschmidt
`10/2003 Summar
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`12/2005 Young
`6/2006 Ferrante
`5/2008 Jalan
`112010 Scharschmidt
`1120 10 Wurtman et al.
`112012 Scharschmidt
`8/2012 Lee
`8/2013 Scharschmidt
`5/20 14 Scharschmidt et a!.
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`
`(Continued)
`Primary Examiner- Jeffrey S Lundgren
`Assistant Examiner- Sara E Townsley
`ABSTRACT
`(57)
`The present disclosure provides methods for adjusting the
`dosage of PAA prodrugs (e.g., HPN-100, PBA) based on
`measurement of PAA and PAGN in plasma and calculating
`the PAA:PAGN ratio so as to determine whether PAA to
`PAGN conversion is satnrated.
`2 Claims, 7 Drawing Sheets
`
`Par Pharmaceutical, Inc. Ex. 1001
`Par v. Horizon, IPR of Patent No. 9,561,197
`Page 1 of 29
`
`

`

`US 9,561,197 B2
`Page 2
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`(56)
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`Page 2 of 29
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`

`

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