IP Library › Granted Patent US 12,365,663
Granted Patent B2
US 12,365,663 · App. 18/438,838 · Granted Jul 22, 2025

Treprostinil derivative compounds and methods of using same

Inventors: Cyrus K. Becker (South San Francisco, CA); Meenakshi S. Venkatraman (South San Francisco, CA); Xiaoming Zhang (South San Francisco, CA); Jürg R. Pfister (South San Francisco, CA); Gwenaella Rescourio (South San Francisco, CA)
Assignee: Corsair Pharma, Inc.
C07D321/00A61K9/0014A61K9/7023A61K31/165A61K31/216A61K31/341A61K31/365A61K45/06C07C59/72C07C69/712C07C69/734C07C69/74C07C69/96C07C219/16C07C235/20C07D207/08C07D211/60C07D257/06C07D263/24C07D263/26C07D265/30C07D295/088C07D295/145C07D307/20C07D317/34C07D317/40C07D453/02C07C2601/02C07C2601/08C07C2601/14C07C2602/42C07C2603/14
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,365,663
App. No.
18/438,838
Granted
Jul 22, 2025
Kind
B2
Abstract

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Claims (24)

1. A compound of Formula I or a pharmaceutically acceptable salt, polymorph or stereoisomer thereof:

wherein:

R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , and R 36 are independently H or deuterium;

Z is —OR 11 , wherein R 11 is branched alkyl, haloalkyl, halocycloalkyl, heteroalkyl, substituted heteroalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, bicycloalkyl, alkylcycloalkyl, substituted alkylcycloalkyl, alkylcycloheteroalkyl, substituted alkylcycloheteroalkyl, alkylaryl, substituted alkylaryl, alkylheteroaryl, substituted alkylheteroaryl, heteroaryl, or substituted heteroaryl, wherein unsubstituted or substituted heteroalkyl is not an unsubstituted or substituted monovalent saturated hydrocarbon group attached to a nitrogen atom, and wherein unsubstituted or substituted alkylaryl is not unsubstituted or substituted benzyl; and

R 1 and R 2 are independently H or P 2 , wherein P 2 is selected from the group consisting of:

wherein:

m is 1, 2, 3, or 4; and

R 14 is independently in each occurrence selected from the group consisting of H, alkyl, cycloalkyl, alkylcycloalkyl, haloalkyl, heteroalkyl, substituted alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, substituted aryl, substituted heteroaryl, substituted arylalkyl, and substituted heteroarylalkyl.

2. The compound of claim 1 , wherein R 11 is bicycloalkyl, alkylcycloalkyl or alkylcycloheteroalkyl.

3. The compound of claim 1 , wherein R 11 is haloalkyl.

4. The compound of claim 3 , wherein R 11 is fluoroalkyl.

5. The compound of claim 1 , wherein R 1 is hydrogen and R 2 is P 2 .

6. The compound of claim 1 , wherein R 1 is P 2 and R 2 is hydrogen.

7. The compound of claim 1 , wherein R 1 is P 2 and R 2 is P 2 .

8. The compound of claim 1 , wherein R 1 and R 2 are each hydrogen.

9. The compound of claim 1 , wherein each of R 20 through R 36 is H.

10. A composition comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers or excipients.

11. The composition of claim 10 , which is formulated for transdermal administration.

12. The composition of claim 11 , which is formulated for transdermal administration via a patch.

13. The composition of claim 10 , wherein the one or more pharmaceutically acceptable carriers or excipients comprise at least one solvent.

14. A method of treating pulmonary hypertension, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of claim 1 .

15. The method of claim 14 , wherein the pulmonary hypertension is pulmonary arterial hypertension.

16. The method of claim 14 , wherein the compound is administered transdermally.

17. The method of claim 16 , wherein the compound is administered transdermally via a patch.

Continuity (9)
Continuation 17965914 · Oct 14, 2022
Continuation 17214460 · Mar 26, 2021
Continuation 16569840 · Sep 13, 2019
Continuation 15811522 · Nov 13, 2017
Continuation 15296164 · Oct 18, 2016
Continuation 14333456 · Jul 16, 2014
Continuation In Part 14153498 · Jan 13, 2014
Provisional Application 61751608 · Jan 11, 2013
Related Publication 20240287018A1 · Aug 29, 2024
References Cited (339)
US 3598122A · Zaffaroni · 1971 [cited by applicant]
US 4144317A · Higuchi et al. · 1979 [cited by applicant]
US 4201211A · Chandrasekaran et al. · 1980 [cited by applicant]
US 4262003A · Urquhart et al. · 1981 [cited by applicant]
US 4306075A · Aristoff · 1981 [cited by applicant]
US 4306076A · Nelson · 1981 [cited by applicant]
US 4338457A · Aristoff · 1982 [cited by applicant]
US 4349689A · Aristoff · 1982 [cited by applicant]
US 4379454A · Campbell et al. · 1983 [cited by applicant]
US 4420632A · Aristoff · 1983 [cited by applicant]
US 4525586A · Aristoff · 1985 [cited by applicant]
US 4668814A · Aristoff · 1987 [cited by applicant]
US 4683330A · Aristoff · 1987 [cited by applicant]
US 5028628A · Tadepalli et al. · 1991 [cited by applicant]
US 5071657A · Oloff et al. · 1991 [cited by applicant]
US 5088977A · Sibalis · 1992 [cited by applicant]
US 5153222A · Tadepalli et al. · 1992 [cited by applicant]
US 5234953A · Crow et al. · 1993 [cited by applicant]
US 5328453A · Sibalis · 1994 [cited by applicant]
US 5797898A · Santini, Jr. et al. · 1998 [cited by applicant]
US 5853751A · Masiz · 1998 [cited by applicant]
US 5972974A · Keenan · 1999 [cited by applicant]
US 6242482B1 · Shorr et al. · 2001 [cited by applicant]
US 6264990B1 · Knepp et al. · 2001 [cited by applicant]
US 6635274B1 · Masiz et al. · 2003 [cited by applicant]
US 6638528B1 · Kanios · 2003 [cited by applicant]
US 6700025B2 · Moriarty et al. · 2004 [cited by applicant]
US 6809223B2 · Moriarty et al. · 2004 [cited by applicant]
US 7199157B2 · Wade et al. · 2007 [cited by applicant]
US 7375139B2 · Aldred · 2008 [cited by applicant]
US 7384978B2 · Phares et al. · 2008 [cited by applicant]
US 7417070B2 · Phares et al. · 2008 [cited by applicant]
US 7537590B2 · Santini, Jr. et al. · 2009 [cited by applicant]
US 7544713B2 · Phares et al. · 2009 [cited by applicant]
US 8232316B2 · Phares et al. · 2012 [cited by applicant]
US 8242305B2 · Phares et al. · 2012 [cited by applicant]
US 8252839B2 · Phares et al. · 2012 [cited by applicant]
US 8349892B2 · Phares · 2013 [cited by applicant]
US 8410169B2 · Phares et al. · 2013 [cited by applicant]
US 8435944B2 · Dipietro et al. · 2013 [cited by applicant]
US 8481782B2 · Batra et al. · 2013 [cited by applicant]
US 8497393B2 · Batra et al. · 2013 [cited by applicant]
US 8519178B2 · Hogan et al. · 2013 [cited by applicant]
US 8524939B2 · Wei et al. · 2013 [cited by applicant]
US 8536363B2 · Phares et al. · 2013 [cited by applicant]
US 8563614B2 · Wade et al. · 2013 [cited by applicant]
US 8591941B2 · Kanios et al. · 2013 [cited by applicant]
US 8609134B2 · Yoneto et al. · 2013 [cited by applicant]
US 8617591B2 · Schacht et al. · 2013 [cited by applicant]
US 8658837B2 · Wei et al. · 2014 [cited by applicant]
US 8747897B2 · Kidane et al. · 2014 [cited by applicant]
US 8748657B2 · Batra et al. · 2014 [cited by applicant]
US 8765813B2 · Wade et al. · 2014 [cited by applicant]
US 8809334B2 · Clozel · 2014 [cited by applicant]
US 8846021B2 · Charles · 2014 [cited by applicant]
US 8877710B2 · Johansson et al. · 2014 [cited by applicant]
US 8940930B2 · Batra et al. · 2015 [cited by applicant]
US 8957240B2 · Hogan et al. · 2015 [cited by applicant]
US 9050311B2 · Phares et al. · 2015 [cited by applicant]
US 9102660B2 · Batra et al. · 2015 [cited by applicant]
US 9156786B2 · Batra et al. · 2015 [cited by applicant]
US 9199908B2 · Phares et al. · 2015 [cited by applicant]
US 9255064B2 · Malinin et al. · 2016 [cited by applicant]
US 9278901B2 · Phares et al. · 2016 [cited by applicant]
US 9278903B2 · Tang et al. · 2016 [cited by applicant]
US 9346738B2 · Jain et al. · 2016 [cited by applicant]
US 9371264B2 · Becker et al. · 2016 [cited by applicant]
US 9394227B1 · Zhang et al. · 2016 [cited by applicant]
US 9422223B2 · Phares et al. · 2016 [cited by applicant]
US 9469600B2 · Malinin et al. · 2016 [cited by applicant]
US 9505704B2 · Gao et al. · 2016 [cited by applicant]
US 9505737B2 · Becker et al. · 2016 [cited by applicant]
US 9643911B2 · Zhang et al. · 2017 [cited by applicant]
US 9701616B2 · Zhang et al. · 2017 [cited by applicant]
US 9776982B2 · Becker et al. · 2017 [cited by applicant]
US 9845305B2 · Becker et al. · 2017 [cited by applicant]
US 9957220B2 · Zhang et al. · 2018 [cited by applicant]
US 10053414B2 · Zhang et al. · 2018 [cited by applicant]
US 10246403B2 · Zhang et al. · 2019 [cited by applicant]
US 10344012B2 · Becker et al. · 2019 [cited by applicant]
US 10450290B2 · Becker et al. · 2019 [cited by applicant]
US 10464877B2 · Zhang et al. · 2019 [cited by applicant]
US 10464878B2 · Zhang et al. · 2019 [cited by applicant]
US 10703706B2 · Zhang et al. · 2020 [cited by applicant]
US 10752605B2 · Becker et al. · 2020 [cited by applicant]
US 10759733B2 · Zhang et al. · 2020 [cited by applicant]
US 10988435B2 · Zhang et al. · 2021 [cited by applicant]
US 11034645B2 · Zhang et al. · 2021 [cited by applicant]
US 11046666B2 · Becker et al. · 2021 [cited by applicant]
US 11339139B2 · Becker et al. · 2022 [cited by applicant]
US 11407707B2 · Zhang et al. · 2022 [cited by applicant]
US 11505535B2 · Becker et al. · 2022 [cited by applicant]
US 11802105B2 · Zhang et al. · 2023 [cited by applicant]
US 11958822B2 · Becker et al. · 2024 [cited by applicant]
US 20020099034A1 · Moriarty et al. · 2002 [cited by applicant]
US 20030108512A1 · Shorr et al. · 2003 [cited by applicant]
US 20040176645A1 · Moriarty et al. · 2004 [cited by applicant]
US 20050080140A1 · Hatae et al. · 2005 [cited by applicant]
US 20050085540A1 · Phares et al. · 2005 [cited by applicant]
US 20050165110A1 · Wade et al. · 2005 [cited by applicant]
US 20050165111A1 · Wade et al. · 2005 [cited by applicant]
US 20050282901A1 · Phares et al. · 2005 [cited by applicant]
US 20070078095A1 · Phares et al. · 2007 [cited by applicant]
US 20070078182A1 · Moriarty et al. · 2007 [cited by applicant]
US 20070082948A1 · Phares et al. · 2007 [cited by applicant]
US 20070254032A1 · Kidane et al. · 2007 [cited by applicant]
US 20080200449A1 · Olschewski et al. · 2008 [cited by applicant]
US 20080249167A1 · Phares et al. · 2008 [cited by applicant]
US 20080280986A1 · Wade et al. · 2008 [cited by applicant]
US 20090036465A1 · Roscigno et al. · 2009 [cited by applicant]
US 20090163738A1 · Batra et al. · 2009 [cited by applicant]
US 20100076083A1 · Olschewski et al. · 2010 [cited by applicant]
US 20100166700A1 · Charles · 2010 [cited by applicant]
US 20100282622A1 · Phares · 2010 [cited by applicant]
US 20100324313A1 · Hogan et al. · 2010 [cited by applicant]
US 20110092599A1 · Wade et al. · 2011 [cited by applicant]
US 20110118213A1 · Phares et al. · 2011 [cited by applicant]
US 20110136818A1 · Clozel · 2011 [cited by applicant]
US 20110268732A1 · Johansson · 2011 [cited by applicant]
US 20110294815A1 · Harbeson · 2011 [cited by applicant]
US 20110319641A1 · Batra et al. · 2011 [cited by applicant]
US 20120010159A1 · Rothblatt et al. · 2012 [cited by applicant]
US 20120129941A1 · Wade et al. · 2012 [cited by applicant]
US 20120184622A1 · Freissmuth et al. · 2012 [cited by applicant]
US 20120190888A1 · Batra et al. · 2012 [cited by applicant]
US 20120197041A1 · Batra et al. · 2012 [cited by applicant]
US 20120216801A1 · Olschewski et al. · 2012 [cited by applicant]
US 20120283470A1 · Batra et al. · 2012 [cited by applicant]
US 20120295980A1 · Phares et al. · 2012 [cited by applicant]
US 20130040898A1 · Johansson · 2013 [cited by applicant]
US 20130053581A1 · Wei et al. · 2013 [cited by applicant]
US 20130096200A1 · Wade et al. · 2013 [cited by applicant]
US 20130165389A1 · Schellenberger et al. · 2013 [cited by applicant]
US 20130184295A1 · Sprague et al. · 2013 [cited by applicant]
US 20130261187A1 · Phares et al. · 2013 [cited by applicant]
US 20130267734A1 · Batra et al. · 2013 [cited by applicant]
US 20130274261A1 · Sands · 2013 [cited by applicant]
US 20130289304A1 · Batra et al. · 2013 [cited by applicant]
US 20130317245A1 · Wei et al. · 2013 [cited by applicant]
US 20130317249A1 · Hogan et al. · 2013 [cited by applicant]
US 20130331593A1 · Mcgowan et al. · 2013 [cited by applicant]
US 20130337534A1 · Charles · 2013 [cited by applicant]
US 20130344038A1 · Freissmuth et al. · 2013 [cited by applicant]
US 20140018430A1 · Freissmuth et al. · 2014 [cited by applicant]
US 20140018431A1 · Wade et al. · 2014 [cited by applicant]
US 20140024856A1 · Giust et al. · 2014 [cited by applicant]
US 20140044797A1 · Johansson et al. · 2014 [cited by applicant]
US 20140193379A1 · Jeffs et al. · 2014 [cited by applicant]
US 20140249093A1 · Vetter et al. · 2014 [cited by applicant]
US 20140256730A1 · Becker et al. · 2014 [cited by applicant]
US 20140275616A1 · Batra et al. · 2014 [cited by applicant]
US 20140288314A1 · Batra et al. · 2014 [cited by applicant]
US 20140296150A1 · Hersel et al. · 2014 [cited by applicant]
US 20140303245A1 · Sprogøe et al. · 2014 [cited by applicant]
US 20140303252A1 · Kidane et al. · 2014 [cited by applicant]
US 20140322207A1 · Johansson et al. · 2014 [cited by applicant]
US 20140323567A1 · Laing · 2014 [cited by applicant]
US 20140329824A1 · Clozel · 2014 [cited by applicant]
US 20150005374A1 · Phares et al. · 2015 [cited by applicant]
US 20150050714A1 · Charles · 2015 [cited by applicant]
US 20150057325A1 · Johansson et al. · 2015 [cited by applicant]
US 20150087686A1 · Tesson et al. · 2015 [cited by applicant]
US 20150087688A1 · Hersel et al. · 2015 [cited by applicant]
US 20150105582A1 · Batra et al. · 2015 [cited by applicant]
US 20150126761A1 · Jain et al. · 2015 [cited by applicant]
US 20150126764A1 · Hogan et al. · 2015 [cited by applicant]
US 20150148414A1 · Malinin et al. · 2015 [cited by applicant]
US 20150166503A1 · Becker et al. · 2015 [cited by applicant]
US 20150175529A1 · Malinin et al. · 2015 [cited by applicant]
US 20150259274A1 · Phares et al. · 2015 [cited by applicant]
US 20150299091A1 · Batra et al. · 2015 [cited by applicant]
US 20150376106A1 · Batra et al. · 2015 [cited by applicant]
US 20160030371A1 · Phares et al. · 2016 [cited by applicant]
US 20160051505A1 · Phares et al. · 2016 [cited by applicant]
US 20160152548A1 · Gao et al. · 2016 [cited by applicant]
US 20160243064A1 · Trehan et al. · 2016 [cited by applicant]
US 20160256425A1 · Malinin et al. · 2016 [cited by applicant]
US 20160289158A1 · Chambournier et al. · 2016 [cited by applicant]
US 20160318844A1 · Malinin et al. · 2016 [cited by applicant]
US 20160355455A1 · Phares et al. · 2016 [cited by applicant]
US 20160368854A1 · Zhang et al. · 2016 [cited by applicant]
US 20160368855A1 · Zhang et al. · 2016 [cited by applicant]
US 20160368889A1 · Becker et al. · 2016 [cited by applicant]
US 20170081303A1 · Becker et al. · 2017 [cited by applicant]
US 20170298001A1 · Zhang et al. · 2017 [cited by applicant]
US 20180016222A1 · Zhang et al. · 2018 [cited by applicant]
US 20180086730A1 · Becker et al. · 2018 [cited by applicant]
US 20180162829A1 · Becker et al. · 2018 [cited by applicant]
US 20180170855A1 · Zhang et al. · 2018 [cited by applicant]
US 20180305293A1 · Zhang et al. · 2018 [cited by applicant]
US 20190010112A1 · Zhang et al. · 2019 [cited by applicant]
US 20190241499A1 · Zhang et al. · 2019 [cited by applicant]
US 20190292163A1 · Becker et al. · 2019 [cited by applicant]
US 20200062726A1 · Becker et al. · 2020 [cited by applicant]
US 20200071257A1 · Zhang et al. · 2020 [cited by applicant]
US 20200095186A1 · Zhang et al. · 2020 [cited by applicant]
US 20200347006A1 · Zhang et al. · 2020 [cited by applicant]
US 20200407336A1 · Becker et al. · 2020 [cited by applicant]
US 20210009501A1 · Zhang et al. · 2021 [cited by applicant]
US 20220112173A1 · Becker et al. · 2022 [cited by applicant]
US 20230331691A1 · Becker et al. · 2023 [cited by applicant]
EP 0496543A2 · 1992 [cited by applicant]
EP 0496548A1 · 1992 [cited by applicant]
EP 1628654A2 · 2006 [cited by applicant]
EP 2252570A1 · 2010 [cited by applicant]
EP 2427054A1 · 2012 [cited by applicant]
EP 2674413A1 · 2013 [cited by applicant]
EP 2792353A2 · 2014 [cited by applicant]
EP 2792353A3 · 2015 [cited by applicant]
EP 2841109A1 · 2015 [cited by applicant]
EP 2861554A2 · 2015 [cited by applicant]
EP 2978313A1 · 2016 [cited by applicant]
EP 3060041A2 · 2016 [cited by applicant]
EP 3068752A1 · 2016 [cited by applicant]
EP 3169660A1 · 2017 [cited by applicant]
EP 2943479B1 · 2020 [cited by applicant]
JP S5420129A · 1979 [cited by applicant]
JP S56138130A · 1981 [cited by applicant]
JP H0687749A · 1994 [cited by applicant]
JP 2003535132A · 2003 [cited by applicant]
JP 2004131499A · 2004 [cited by applicant]
JP 2007501281A · 2007 [cited by applicant]
JP 2010527987A · 2010 [cited by applicant]
JP 2010531293A · 2010 [cited by applicant]
JP 2011506599A · 2011 [cited by applicant]
JP 2013528621A · 2013 [cited by applicant]
JP 6542128B2 · 2019 [cited by applicant]
JP 6561109B2 · 2019 [cited by applicant]
JP 2019194204A · 2019 [cited by applicant]
JP 2020011957A · 2020 [cited by applicant]
WO 0057701A1 · 2000 [cited by applicant]
WO 0193862A1 · 2001 [cited by applicant]
WO 02053517A2 · 2002 [cited by applicant]
WO 02053517A3 · 2003 [cited by applicant]
WO 03049676A2 · 2003 [cited by applicant]
WO 03049676A3 · 2003 [cited by applicant]
WO 2005007081A2 · 2005 [cited by applicant]
WO 2005007081A3 · 2005 [cited by applicant]
WO 2005058303A1 · 2005 [cited by applicant]
WO 2005058329A1 · 2005 [cited by applicant]
WO 2007100902A2 · 2007 [cited by applicant]
WO 2007127216A2 · 2007 [cited by applicant]
WO 2007134292A2 · 2007 [cited by applicant]
WO 2007127216A3 · 2007 [cited by applicant]
WO 2007134292A3 · 2008 [cited by applicant]
WO 2008002929A2 · 2008 [cited by applicant]
WO 2008049000A2 · 2008 [cited by applicant]
WO 2008002929A3 · 2008 [cited by applicant]
WO 2008098196A1 · 2008 [cited by applicant]
WO 2007100902A3 · 2008 [cited by applicant]
WO 2009001968A1 · 2008 [cited by applicant]
WO 2008049000A3 · 2009 [cited by applicant]
WO 2009078965A1 · 2009 [cited by applicant]
WO 2009152160A1 · 2009 [cited by applicant]
WO 2009158010A1 · 2009 [cited by applicant]
WO 2010018549A2 · 2010 [cited by applicant]
WO 2010018549A3 · 2010 [cited by applicant]
WO 2010075861A2 · 2010 [cited by applicant]
WO 2010075861A3 · 2010 [cited by applicant]
WO 2010129757A1 · 2010 [cited by applicant]
WO 2011005505A2 · 2011 [cited by applicant]
WO 2011015630A1 · 2011 [cited by applicant]
WO 2011005505A3 · 2011 [cited by applicant]
WO 2011123813A2 · 2011 [cited by applicant]
WO 2011134478A2 · 2011 [cited by applicant]
WO 2011123813A3 · 2011 [cited by applicant]
WO 2011134478A3 · 2011 [cited by applicant]
WO 2011153363A1 · 2011 [cited by applicant]
WO 2012006273A1 · 2012 [cited by applicant]
WO 2012009816A1 · 2012 [cited by applicant]
WO 2012041334A1 · 2012 [cited by applicant]
WO 2012088607A1 · 2012 [cited by applicant]
WO 2012095511A1 · 2012 [cited by applicant]
WO 2012107363A1 · 2012 [cited by applicant]
WO 2012107364A1 · 2012 [cited by applicant]
WO 2012143012A1 · 2012 [cited by applicant]
WO 2013022846A2 · 2013 [cited by applicant]
WO 2013024051A1 · 2013 [cited by applicant]
WO 2013024052A1 · 2013 [cited by applicant]
WO 2013024053A1 · 2013 [cited by applicant]
WO 2013022846A3 · 2013 [cited by applicant]
WO 2013143548A1 · 2013 [cited by applicant]
WO 2013160340A1 · 2013 [cited by applicant]
WO 2013174848A2 · 2013 [cited by applicant]
WO 2014022373A1 · 2014 [cited by applicant]
WO 2013174848A3 · 2014 [cited by applicant]
WO 2014089385A2 · 2014 [cited by applicant]
WO 2014110094A1 · 2014 [cited by applicant]
WO 2014110491A1 · 2014 [cited by applicant]
WO 2014089385A3 · 2014 [cited by applicant]
WO 2014150203A1 · 2014 [cited by applicant]
WO 2014160638A1 · 2014 [cited by applicant]
WO 2014179295A1 · 2014 [cited by applicant]
WO 2014203278A2 · 2014 [cited by applicant]
WO 2014203278A3 · 2015 [cited by applicant]
WO 2015061720A2 · 2015 [cited by applicant]
WO 2015073314A1 · 2015 [cited by applicant]
WO 2015061720A3 · 2015 [cited by applicant]
WO 2015138423A1 · 2015 [cited by applicant]
WO 2015138423A9 · 2015 [cited by applicant]
WO 2016010538A1 · 2016 [cited by applicant]
WO 2016055819A1 · 2016 [cited by applicant]
WO 2016081658A1 · 2016 [cited by applicant]
WO 2016120311A1 · 2016 [cited by applicant]
WO 2016176555A1 · 2016 [cited by applicant]
WO 2016205202A1 · 2016 [cited by applicant]
WO 2018106632A1 · 2018 [cited by applicant]
Ash et al., “Handbook of Pharmaceutical Additives,” 3rd Edition. Synapse Information Resources, Inc., 2007, 3 pages. [cited by applicant]
Buckley et al., “Phosphodiesterase-5 Inhibitors in Management of Pulmonary Hypertension: Safety, Tolerability, and Efficacy,” Drug, Healthcare and Patient Safety, 2010, vol. 2, pp. 151-161. [cited by applicant]
Cochrane et al., “A Macrolactonization Approach to the Total Synthesis of the Antimicrobial Cyclic Depsipeptide LI-F04a and Diastereoisomeric Analogues,” Beilstein Journal of Organic Chemistry, 2012, vol. 8, pp. 1344-13… [cited by applicant]
Doh et al., “Synthesis and Evaluation of Ketorolac Ester Prodrugs for Transdermal Delivery,” Journal of Pharmaceutical Sciences, May 2003, vol. 92, No. 5, pp. 1008-1017. [cited by applicant]
Dupuis et al., “Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension,” European Respiratory Journal, European Respiratory Society, 2008, vol. 31, No. 2, pp. 407-415. [cited by applicant]
Extended European Search Report in EP20166678.1, mailed Aug. 11, 2020 7 pages. [cited by applicant]
Extended European Search Report in EP20202064.0, mailed Apr. 21, 2021, 14 pages. [cited by applicant]
Findlay et al., “Radioimmunoassay for the Chemical Stable Prostacyclin Analog, 15AU81: a Preliminary Pharmacokinetics Study in the Dog,” Prostaglandins Leukotrienes and Essential Fatty Acids, 1993, vol. 48, No. 2, pp. 1… [cited by applicant]
Gannes et al., “Natural Abundance Variations in Stable Isotopes and their Potential Uses in Animal Physiological Ecology,” Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 1998, vol. 1… [cited by applicant]
Geiger et al., “Targeting of the Prostacyclin Specific IP1 Receptor In Lungs with Molecular Conjugates Comprising Prostaglandin I2 Analogues,” Biomaterials, 2010, vol. 31, pp. 2903-2911. [cited by applicant]
Gibson, M., “Pharmaceutical Pre-formulation and Formulation,” CRC Press LLC, 2004, 610 pages. [cited by applicant]
Guarino, V., “The Molecular Design of Prodrugs by Functional Group,” Edited by Jarkko Rautio, Products and Targeted Delivery: Towards Better ADME Properties, vol. 47, Dec. 15, 2010, pp. 31-60. [cited by applicant]
International Preliminary Report on Patentability in PCT/US2014/011260, mailed Jul. 23, 2015, 8 pages. [cited by applicant]
International Preliminary Report on Patentability in PCT/US2014/046920, mailed Jan. 26, 2017, 11 pages. [cited by applicant]
International Search Report and Written Opinion in PCT/US2014/011260, Jun. 5, 2014, 10 pages. [cited by applicant]
International Search Report and Written Opinion in PCT/US2014/046920, mailed Dec. 22, 2014, 15 pages. [cited by applicant]
Invitation to Pay Additional Fees with Partial International Search Report in PCT/US2014/046920, mailed Sep. 11, 2014, 7 pages. [cited by applicant]
Office Action in JP2019134245, mailed Jul. 27, 2020, 10 pages. [cited by applicant]
Office Action in JP2020178704, mailed Sep. 1, 2021, 11 pages. [cited by applicant]
Office Action in JP2022141117, mailed Aug. 23, 2023, 10 pages. [cited by applicant]
Paudel et al., “Challenges and Opportunities in Dermal/Transdermal Delivery,” Therapeutic Delivery, Jul. 2010, vol. 1, No. 1, pp. 109-131. [cited by applicant]
Pearson et al., “Handbook of Reagents of Organic Synthesis: Activating Agents and Protecting Groups,” John Wiley & Sons, 1999, 4 pages. [cited by applicant]
Rautio et al., “Prodrugs: Design and Clinical Applications,” Nature Reviews: Drug Discovery, Mar. 2008, vol. 7, pp. 255-270. [cited by applicant]
Remington, “The Science and Practice of Pharmacy,” 21st ed., Lippincott Williams & Wilkins, 2005, 5 pages. [cited by applicant]
Rowe et al., “Handbook of Pharmaceutical Excipients,” 5th Edition, The Pharmaceutical Press and the American Pharmaceutical Association, 2005, 945 pages. [cited by applicant]
Schanz et al., “Topical Treatment of Erectile Dysfunction with Prostaglandin E1 Ethyl Ester,” Journal of German Society of Dermatology, 2009, vol. 7, No. 12, pp. 1055-1059. [cited by applicant]
Shiina, I., “Total Synthesis of Natural 8- and 9-Membered Lactones: Recent Advancements in Medium-Sized Ring Formation,” Chemical Reviews, 2007, vol. 107, pp. 239-273. [cited by applicant]
Shorr et al., “Prostaglandin Compounds and Derivatives for the Treatment of Congestive Heart Failure,” Caplus, Chemical Abstracts Service, Columbus, Ohio, Accession Number: 2001:408054, Document No. 135:14327, retrieved… [cited by applicant]
Smith et al., “March's Advanced Organic Chemistry: Reactions, Mechanisms and Structure,” 6th Edition, A John Wiley & Sons, 2007, 4 pages. [cited by applicant]
Thayer, A., “Form and Function,” Chemical & Engineering News, Jun. 18, 2007, vol. 85, No. 25, Retrieved from the Internet: <http://cen.acs.org/articles/85/i25/Form-Function.html>, pp. 17-30. [cited by applicant]
Wada et al., “Natural Abundance of Carbon, Nitrogen, and Hydrogen Isotope Ratios in Biogenic Substances: Present and Future,” Seikagaku, The Japanese Biological Society, 1994, vol. 66, No. 1, pp. 15-29. [cited by applicant]
Wuts et al., “Greene's Protective Groups in Organic Synthesis,” 4th Edition, A John Wiley & Sons, 2007, 5 pages. [cited by applicant]