(12) United States Patent
`(10) Patent No.:
`US 9,138,456 B2
`
`O’Connor et al.
`(45) Date of Patent:
`Sep. 22, 2015
`
`USOO9138456B2
`
`(54) LIPOPEPTIDE COMPOSITIONS AND
`RELATED METHODS
`
`.
`.
`.
`(71) Applicant: EublsttPhaK/Irriagsléglcals, Inc.,
`ex1ng 011,
`
`(72)
`
`Inventors: Sandra O’Connor, Hudson, NH (US);
`Sophie Sun, Lexington, MA (US);
`Gaauri Naik Cambridge MA (US)
`’
`’
`_
`_
`.
`(73) A551gnee: Cublst Pharmaceutlcals LLC,
`KenilWOI‘th, NJ (US)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent IS extended or adjusted under 35
`USC 154(b)by Odays
`
`(21) Appl. No.: 14/096,346
`
`(22) “let
`
`(65)
`
`Dec-4,2013
`,
`,
`,
`Pm" PUbllcatlon Data
`
`US 2014/0364380 A1
`
`1360 11’ 2014
`
`5,336,756 A
`5,387,670 A
`5,629,288 A
`5,912,226 A
`5,955,509 A
`6,194,383 B1
`6,468,967 B1
`6,696,412 Bl
`6,716,962 B2
`6,852,689 B2
`RE39,071 E
`7,138,487 B2
`7,279,597 B1
`8,003,673 B2
`8,058,238 B2
`Séggagfi E;
`8:431:539 B2
`8,604,164 B2
`8,835,382 B2
`2002/0111311 A1
`2002/0132762 A1
`
`3883883223”; :1
`2004/0067878 A1
`2004/0077601 A1
`2004/0242467 A1
`2005/0009747 A1
`2005/0027113 A1
`
`8/1994 Schwartz et a1.
`2/1995 Roy et a1.
`5/1997 Lattrell et a1.
`6/1999 Baker et a1.
`9/1999 Webber et a1.
`2/2001 Hammann et a1.
`10/2002 Oleson et al.
`2/2004 Kelleher
`4/2004 Borders et a1.
`2/2005 Oleson et a1.
`4/2006 Baker et a1.
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`8/2011 Alder et al.
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`1i/2812 5153111133;
`4/2013 Palepu et 31.
`12/2013 Kelleher et a1.
`9/2014 O’Connor et al.
`8/2002 Govardhan et al.
`9/2002 Borders
`
`$883 E213
`4/2004 Hill
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`12/2004 Borders
`1/2005 Kelleher
`2/2005 Miao et al.
`
`Related US. Application Data
`
`2005/0152979 A1
`2005/0196418 A1
`
`7/2005 Besman et al.
`9/2005 Yu
`
`filed as
`(62) Division of application No. 13/511,246,
`application No. PCT/US2010/057910 on Nov. 23,
`
`(Continued)
`
`(60) Provisional application No. 61/263,784, filed on Nov.
`23 2009
`’
`'
`
`CA
`CN
`
`2675622 A1
`1592753 A
`
`8/2008
`3/2005
`
`(51)
`
`(2006.01)
`(2006.01)
`(2006.01)
`(388281)
`E20064”;
`'
`(2006-01)
`(2006.01)
`(2006.01)
`
`Int. Cl.
`A61K 38/12
`C07K 7/50
`A61K 9/00
`jig; 3/71/296
`A61K 38/10
`A61K 9/08
`A61K 3 8/00
`C07K 11/02
`(52) US. Cl.
`CPC ............... A61K 38/12 (2013.01); A61K 9/0019
`(2013.01); A61K 9/19 (2013.01); A61K38/10
`(2013.01);A61K47/26 (2013.01);A61K 9/00
`.
`.
`(201301)3 A61K 9/08 (201301)3 A61K 38/00
`(2013-01); C07K 11/02 (201301)
`(58) Field of Classification Search
`CPC ......... A61K 9/0019; A61K 9/08; A61K 9/19;
`A61K 38/00; A61K 47/26; A61K 9/00;
`A61K 38/10; A61K 38/12; C07K11/02
`See application file for complete search history.
`
`H
`
`(Continued)
`OTHER PUBLICATIONS
`bl' h d
`f
`_
`_
`_
`f
`d
`d
`111
`.
`actose, rom Dietitians 0 Cana a, pp. 1-3, pu is e
`Pogofgukrce 0
`Source of sucrose, from http://wwwehowcom/about75376127,
`s0urces-sucr0se.html, pp. 1-2, accessed Nov. 7, 2014*
`Mannitol,
`from http://wwwdrugs.com/inactive/mannito1-142.
`html?printable:1, pp. 1-2, accessed Nov. 7, 2014*
`Richards et a1, Trehalose: a review of properties, history of use and
`human tolerance, and results of multiple safety studies, Food and
`Chemical Toxicology, 2002, 40, pp. 871-898.*
`Watera from httPI//WWW~biglogy-0nlineorg/dictionaryWatera PP~
`é'3’ afclesffgl Aplr' 24’ 2?“;
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`31’ 0mm“ mg .r.° 1”
`Immediate Reconstitution, Room Temperature Product Stability and
`Reconstitution Stability”, AAPS 201 1, Abstract for Poster NO. T3328
`Published
`Abstract:
`http://abstracts.aaps.0rg/SecureVieW/
`AAPSJournal/vmqutdm9e4880v6bthy.pdf.
`(Continued)
`
`Primary Examiner 7 Julie Ha
`Assistant Examiner 7 Li Ni Komatsu
`
`(56)
`
`R f
`e erences
`
`C't d
`1 e
`
`(74) Attorney, Agent, orFirm 7 Dianne Pecoraro; Laura M.
`Ginkel
`
`U.S. PATENT DOCUMENTS
`
`(57)
`
`ABSTRACT
`
`4,331,594 A
`4,439,425 A
`4,482,487 A
`4,537,717 A
`4,874,843 A
`4,882,164 A
`5,271,935 A
`
`5/1982 Hamill et al.
`3/1984 Tarcsay et a1.
`11/1984 Abbott et 31.
`8/ 1985 Abbott et a1.
`10/1989 Baker et a1.
`11/1989 Ferro
`12/1993 Franco et a1.
`
`The present disclosure prov1des novel povvder daptomycm
`formulations which have improved chemical stability and
`faster reconstitution times when in the solid state. Some
`examples of the compositions comprise daptomycin and
`sucrose.
`
`15 Claims, 22 Drawing Sheets
`
`AMNEAL EX. 1001
`
`AMNEAL EX. 1001
`
`

`

`US 9,138,456 B2
` Page 2
`
`(56)
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`_
`53882 $6131
`aya
`“2006 Vaya
`135882 :aya B
`fly e
`‘ione'
`1 5388: grlledman
`6/2007 13:12:; al
`$588; $331313
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`5882/8322??? :1
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`
`'
`
`FOREIGN PATENT DOCUMENTS
`
`CN
`CN
`EP
`EP
`EP
`EP
`EP
`EP
`JP
`EP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`WO
`W0
`WO
`$8
`W0
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`WO
`
`1616083 A
`101330905 A
`0178152
`0294990
`0386951 A2
`0511866
`0521408
`0629636
`64047388
`1252179
`04224197
`H05-194257 A
`05239090
`05271284
`H10.212241 A
`2003-095975 A
`2005-060377 A
`93/10809 A1
`WO9321207
`97/45135 A1
`38333332?
`W0 9940113
`WO9943700
`W0 0018419
`W001/44274 A1
`W0 01/53330
`W001/53330 A2
`W00153330
`W002/055537 A1
`WOW/056829 A2
`WOW/059145 A1
`W002059145
`WOW/096936 A2
`W002096936
`WO2004/004658 A2
`WO2006/084174 A2
`WO2006/084174 A3
`WO2007/061529 A1
`WO2007/099396 A2
`WO2007/099396 A3
`2008/102849 A1
`
`W02008/127291 A2
`wogggg1534217$ :3
`WO2009144739 A1
`WO2011/019839 A2
`WO2011/035108 A1
`WO2011/062676 A1
`WO2011/063419 A2
`WO2012/061360 A2
`WO2012/088441 A1
`WO2012/112319 A1
`
`5/2005
`12/2008
`4/ 1986
`12/1988
`3/1989
`11/1992
`“1993
`12/1994
`2/1989
`10/2002
`8/1992
`8/1993
`9/1993
`10/1993
`8/1998
`4/2003
`3/2005
`6/1993
`10/1993
`12/1997
`31333
`8/1999
`9/1999
`4/2000
`6/2001
`7/2001
`7/2001
`7/2001
`7/2002
`7/2002
`8/2002
`8/2002
`12/2002
`12/2002
`1/2004
`8/2006
`8/2006
`5/2007
`9/2007
`9/2007
`8/2008
`
`10/2008
`13/3883
`12/2009
`2/2011
`3/2011
`5/2011
`5/2011
`5/2012
`6/2012
`8/2012
`
`AMNEAL EX. 1001
`
`

`

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`AMNEAL EX. 1001
`
`AMNEAL EX. 1001
`
`

`

`US 9,138,456 B2
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`Staphylococcus aureus, Vancomycin-Resistant Ehterococcus fac—
`cium, and Methicillin-Resistant Staphylococcus aureus Isolates in an
`In Vitro Pharmacodynamic Model with Simulated Endocardial Veg-
`etations; Antimicrobial Agents and Chemotherapy; 2001, vol. 45, pp.
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`Arbeit et al., The Safety and Efficacy of Daptomycin for the Treat-
`ment of Complicated Skin and Skin-Structure Infections; Clinical
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`Auwera et al., Ex-vivo study of serum bactericidal titers and kiilling
`rates of daptomycin (LY146032) combined or not combined with
`amikacin compared with those ofvancomycin; Antimicrobial Agents
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`Barry et al., In vitro activities of daptomycin against 2,789 clinical
`isolates from 11 North American Medical Centers; Antimicrobial
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`Benvenuto et al., Pharmacokinetics and Tolerability of Daptomycin
`at Doses up to 12 Milligrams per Kilogram of Body Weight Once
`Daily in Healthy Volunteers; Antimicrobial Agents and Chemo-
`therapy; 2006, vol. 50, pp. 3245-3249.
`Dvorchik et al., Daptomycin Pharmacokinetics and Safety following
`Administration of Escalating Doses Once Daily to Healthy Subjects;
`Antimicrobial Agents and Chemotherapy; 2003, vol. 47, pp. 1318-
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`Bingen et al., Bactericidal activity of Fancomycin, Daptomycin,
`Ampicillin and Aminoglycosides against Vancomycin-resistant
`Enterecoccus; J of Antimicrobial Chemotherapy; 1990, vol. 26, pp.
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`Bryant et al., Effect of Abscess Milieu on Bactericidal Activity of
`IXl46032 against Staphylococci; Eur. J. Clin. Microbiol.; 1987, vol.
`6, pp. 186-188.
`CaballeroiGranado et al.; Case-control Study ofRisk Factors for the
`Development of Enterococcal Bacteremia; Eur. J. Clin. Microbiol.
`Infect. Dis. 2001, vol. 20, p. 83-90.
`Caron et al.; Daptomycin or teicoplanin in combination with
`gentamicin for treatment of experiemental endocarditis due to highly
`glycopeptide-resistant isolate of Ehterococcus faecium; Antimicro-
`bial Agents and Chemotherapy; 1992, vol. 36, pp. 2611-2616.
`Carter et al., Protein Crystallization Using Incomplete Factorial
`Experiments; J. Biol. Chem., 1979, vol. 254, pp. 12219-12223.
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`Chayen et al.; Recent advances in methodology for the crystallization
`of biological macromolecules; Journal of Crystal Growth; 1999, pp.
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`Crompton et al., Outocmes with daptomycin in the treatment of
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`Journal of Antimicrobial Chemotherapy; 2010, vol. 65, pp. 1784-
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`and Vancomycin
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`Staphylococcus aureus; Antimicrobial Agents and Chemotherapy;
`2006, vol. 50, pp. 1079-1082.
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`(MRSA) mitral valve acute bacterial endocarditis (ABE); Eur. J. Clin.
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`Practical Approach, 2d ed., 1999, pp. 92-95, 4 pages.
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`against Enterococci isolated from blood and urine, Can. J. Infect.
`Dis., 1992, vol. 3, pp. 173-178.
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`Application No. 2012-540161, 4 pages.
`
`* cited by examiner
`
`AMNEAL EX. 1001
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`AMNEAL EX. 1001
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`

`

`US. Patent
`
`Sep. 22, 2015
`
`Sheet 1 of 22
`
`US 9,138,456 B2
`
`Daptomycin
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`0
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`AMNEAL EX. 1001
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`AMNEAL EX. 1001
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`

`

`US. Patent
`
`Sep. 22, 2015
`
`Sheet 2 of 22
`
`US 9,138,456 B2
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`AMNEAL EX. 1001
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`

`

`US. Patent
`
`Sep. 22, 2015
`
`Sheet 3 of 22
`
`US 9,138,456 B2
`
`“IS-isomer” or “Is-isomer of daptomycin”
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`AMNEAL EX. 1001
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`AMNEAL EX. 1001
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`

`

`US. Patent
`
`Sep. 22, 2015
`
`Sheet 4 of 22
`
`US 9,138,456 B2
`
`lactone hydrolysis product
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`
`AMNEAL EX. 1001
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`AMNEAL EX. 1001
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 5 of 22
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`US 9,138,456 B2
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`2B
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 8 of 22
`
`US 9,138,456 B2
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 9 of 22
`
`US 9,138,456 B2
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 10 0f 22
`
`US 9,138,456 B2
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 11 0f 22
`
`US 9,138,456 B2
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`

`

`U.S. Patent
`
`Sep. 22, 2015
`
`Sheet 12 0f 22
`
`US 9,138,456 B2
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