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`
`
`
`FOREIGN PATJN 1 DOCUMJNTS
`1592753 A
`3/2005
`1616083 A *
`/2005
`
`(54) LIPOPEPTIDE COIVIPOSITIONS AND
`RELATED lVlETHODS
`
`(75)
`
`Inventors: S‘andra 9’Connor, Hudson, NPI (US);
`50Phle bun, Lexmgton, MA (US);
`Gaauri Naik, Cambridge, MA (US)
`
`(73) Assignee: Cubist Pharmaceuticals, Inc.,
`L .
`I MA US
`cxmg on,
`1
`(
`)
`Subject to any disclaimer, the term ofthjs
`patent is extended or adjusted under 35
`U.S.C. 154(1)) by 0 days.
`
`( * ) Notice:
`
`(21) APP1~ N04
`_
`(22) PCT Filed:
`
`13/511346
`
`V0". 23, 2010
`
`(86) PCT N0.:
`§371 (c)(1),
`(2), (4) Date:
`i
`
`PC'l'lU82010/057910
`
`Ju]_10, 2012
`
`.
`(87) PCT PUb' N0" “102°11’06“”
`PCT Pub. Date: May 26 2011
`A
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`Prior Publication Data
`
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`
`US 2012/0270772 A1
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`Oct. 25, 2012
`.
`.
`Relate‘i U'S' APPhcatmn Data
`
`CN
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`
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`
`(Continued)
`OTI IER PUBLICATIONS
`
`(51)
`
`(2006.01)
`(2006 01)
`(200601)
`'
`$38238
`'
`
`Int. Cl.
`A 61K 38/12
`A61K 58/10
`A61P 31/04
`it???gig/32
`(52) U'S' Cl'
`CPC ................. A61K38/12 (2013.01); A61K38/I0
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`
`Primary Examiner 7 Julie Ha
`Assistant Examiner 7 Li Ni Komatsu
`
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`
`(57)
`
`ABSTRACT
`,
`,
`,
`The present d1sc10sure prov1dcs novel powder daptomycm
`formulations which have improved chemical stability and
`-
`--
`-
`-
`faster reconstitution times when in the solid state. Some
`examples oi the comp051t1ons comprlse daptomycm and
`sucrose.
`
`18 Claims, 22 Drawing Sheets
`
`AMNEAL EX. 1009
`
`AMNEAL EX. 1009
`
`

`

`US 8,835,382 B2
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`
`* cited by examiner
`
`AMNEAL EX. 1009
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`

`US. Patent
`
`Sep. 16, 2014
`
`Sheet 1 of 22
`
`US 8,835,382 B2
`
`Daptomycin
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`0
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`HM
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`AMNEAL EX. 1009
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`AMNEAL EX. 1009
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`

`

`US. Patent
`
`Sep. 16, 2014
`
`Sheet 2 of 22
`
`US 8,835,382 B2
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`“anhydro-daptomycin”
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`

`US. Patent
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`Sep. 16, 2014
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`Sheet 3 of 22
`
`US 8,835,382 B2
`
`“[3-isomer” or “[3-isomer of daptomycin”
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`AMNEAL EX. 1009
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`

`US. Patent
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`Sep. 16, 2014
`
`Sheet 4 of 22
`
`US 8,835,382 B2
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`lactone hydrolysis product
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`AMNEAL EX. 1009
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`

`US. Patent
`
`Sep. 16, 2014
`
`Sheet 5 of 22
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`US 8,835,382 B2
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`US. Patent
`
`Sep. 16, 2014
`
`Sheet 6 of 22
`
`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
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`Sheet 7 of 22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
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`Sheet 8 of 22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
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`Sheet 9 of 22
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`US 8,835,382 B2
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`

`US. Patent
`
`Sep. 16, 2014
`
`Sheet 10 0f 22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
`
`Sheet]],0f22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
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`Sheet 12 0f 22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
`
`Sheet 13 0f 22
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`US 8,835,382 B2
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`Sep. 16, 2014
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`Sheet 14 0f 22
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`US 8,835,382 B2
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`US. Patent
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`Sep. 16, 2014
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`Sheet 15 of 22
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`US 8,835,382 B2
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`

`US. Patent
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`Sep. 16, 2014
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`Sheet 16 0f 22
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`US 8,835,382 B2
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