Granted Patent
B2
US 12,629,357 · App. 17/996,575 · Granted May 19, 2026
Treatment of viral infections, of organ injury, and of related conditions using a HIF prolyl hydroxylase inhibitor or a HIF-alpha stabilizer
Assignee:
Akebia Therapeutics, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Disclosed herein are new therapeutic methods comprising administering compounds that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH). In particular, methods described herein can be useful for treating/preventing a disease or condition in patients in need thereof, such as a patient having a viral infection such as a respiratory and/or pulmonary viral infection (e.g., an infection such as COVID-19 or a coronavirus infection). Methods described herein can also be useful for treating/preventing organ injury (e.g. organ injury that occurs concurrently or as a result of an infection). For example, methods described herein can be useful for treating or preventing acute lung injury, acute respiratory distress syndrome (ARDS), cardiovascular injury, injury to the liver, kidney diseases, and/or multi-organ failure.
Claims (23)
1 . A method of treating or preventing a lung disease that is acute respiratory distress syndrome (ARDS) in a patient having a respiratory viral infection, comprising administering to the patient a compound that is a HIF prolyl hydroxylase inhibitor or a HIF-alpha stabilizer that is vadadustat (AKB-6548),
or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the respiratory viral infection is COVID-19.
3 . The method of claim 1 , wherein the ARDS is induced by or associated with the viral infection.
4 . A method of treating or preventing a lung disease that is acute respiratory distress syndrome (ARDS) in a patient infected with a coronavirus, comprising administering to the patient a compound that is a HIF prolyl hydroxylase inhibitor or a HIF-alpha stabilizer that is vadadustat (AKB-6548),
or a pharmaceutically acceptable salt thereof.
5 . The method of claim 4 , wherein the patient is infected with SARS-COV-2.
6 . The method of claim 4 , wherein the ARDS is induced by or associated with the viral infection.
7 . The method of claim 1 , wherein vadadustat (AKB-6548) is administered at a dose of 150 mg to 1000 mg, of 150 mg to 1800 mg per day, or of 900-1800 mg per day.
8 . The method of claim 7 , wherein vadadustat (AKB-6548) is administered at an initial dose of 900 mg per day.
9 . The method of claim 7 , comprising administration of vadadustat (AKB-6548) a dose of 900-1800 mg per day.
10 . The method of claim 7 , wherein vadadustat (AKB-6548) is administered to the patient for up to about one month.
11 . The method of claim 4 , wherein vadadustat (AKB-6548) is administered at a dose of 150 mg to 1000 mg, of 150 mg to 1800 mg per day, or of 900-1800 mg per day.
12 . The method of claim 11 , wherein vadadustat (AKB-6548) is administered at an initial dose of 900 mg per day.
13 . The method of claim 11 , comprising administration of vadadustat (AKB-6548) a dose of 900-1800 mg per day.
14 . The method of claim 11 , wherein vadadustat (AKB-6548) is administered to the patient for up to about one month.
15 . A method for treating or preventing acute respiratory distress syndrome (ARDS) in a patient in need thereof, wherein the method comprises administering a compound that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH) that is vadadustat,
16 . The method of claim 15 , wherein the acute respiratory distress syndrome (ARDS) is characterized by accumulation of inflammatory cells into the lungs, cytokine release, inflammatory activation of recruited or resident cells, disruption of the alveolar-capillary barrier function, pulmonary edema, attenuated gas exchange, or lung inflammation, or any combination thereof.
17 . The method of claim 15 , comprising administering to said patient a once daily dose of vadadustat that is between 900 mg to 1800 mg.
18 . The method of claim 17 , comprising administering to said patient an initial dose of 900 mg vadadustat.
19 . The method of claim 17 , comprising administering to said patient a once daily dose of 900 mg vadadustat.
20 . The method of claim 19 , comprising administering to said patient vadadustat for up to about one month.
21 . The method of claim 20 , wherein the patient receives a once daily dose of about 900 mg vadadustat throughout the period of treatment.
Assignments (2)
SECURITY INTEREST
Recorded Jan 29, 2024
From: AKEBIA THERAPEUTICS, INC.; KERYX BIOPHARMACEUTICALS, INC.
To: KREOS CAPITAL VII (UK) LIMITED
Reel/Frame 066377/0654 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 26, 2023
From: BURKE, STEVEN; RABINOWITZ, MICHAEL
To: AKEBIA THERAPEUTICS, INC.
Reel/Frame 062493/0789 →
Continuity (4)
Provisional Application
63047501
· Jul 2, 2020
Provisional Application
63022890
· May 11, 2020
Provisional Application
63012839
· Apr 20, 2020
References Cited (400)
US 3655679A
· Shen et al.
· 1972
[cited by applicant]
US 3703582A
· Shen et al.
· 1972
[cited by applicant]
US 3894920A
· Kondo et al.
· 1975
[cited by applicant]
US 4016287A
· Eberhardt et al.
· 1977
[cited by applicant]
US 4764522A
· Imhof et al.
· 1988
[cited by applicant]
US 5397799A
· Kress et al.
· 1995
[cited by applicant]
US 5405613A
· Rowland
· 1995
[cited by applicant]
US 5607954A
· Weidmann et al.
· 1997
[cited by applicant]
US 5610172A
· Weidmann et al.
· 1997
[cited by applicant]
US 5620995A
· Weidmann et al.
· 1997
[cited by applicant]
US 5620996A
· Weidmann et al.
· 1997
[cited by applicant]
US 5658933A
· Weidmann et al.
· 1997
[cited by applicant]
US 5719164A
· Weidmann et al.
· 1998
[cited by applicant]
US 5726305A
· Weidmann et al.
· 1998
[cited by applicant]
US 6020350A
· Weidmann et al.
· 2000
[cited by applicant]
US 6093730A
· Weidmann et al.
· 2000
[cited by applicant]
US 6159379A
· Means et al.
· 2000
[cited by applicant]
US 6420427B1
· Takahashi et al.
· 2002
[cited by applicant]
US 6566088B1
· McKnight et al.
· 2003
[cited by applicant]
US 6589758B1
· Zhu
· 2003
[cited by applicant]
US 6855510B2
· Kaelin et al.
· 2005
[cited by applicant]
US 7183287B2
· Durley
· 2007
[cited by applicant]
US 7307060B2
· Compernolle et al.
· 2007
[cited by applicant]
US 7323475B2
· Arend et al.
· 2008
[cited by applicant]
US 7402696B2
· Suzuki et al.
· 2008
[cited by applicant]
US 7588924B2
· Evdokimov et al.
· 2009
[cited by applicant]
US 7618940B2
· Fourney et al.
· 2009
[cited by applicant]
US 7625927B2
· Klimko et al.
· 2009
[cited by applicant]
US 7629357B2
· Arend et al.
· 2009
[cited by applicant]
US 7662854B2
· Schofield et al.
· 2010
[cited by applicant]
US 7696223B2
· Deng et al.
· 2010
[cited by applicant]
US 7811595B2
· Kawamoto et al.
· 2010
[cited by applicant]
US 7897612B2
· Fitch et al.
· 2011
[cited by applicant]
US 7928120B2
· Arend et al.
· 2011
[cited by applicant]
US 8050873B2
· Evdokimov et al.
· 2011
[cited by applicant]
US 8124582B2
· Guenzler-Pukall et al.
· 2012
[cited by applicant]
US 8217043B2
· Deng et al.
· 2012
[cited by applicant]
US 8269008B2
· Arend et al.
· 2012
[cited by applicant]
US 8273773B2
· Brameld et al.
· 2012
[cited by applicant]
US 8283465B2
· Mitani et al.
· 2012
[cited by applicant]
US 8309537B2
· Gardner et al.
· 2012
[cited by applicant]
US 8314103B2
· Kumar et al.
· 2012
[cited by applicant]
US 8323671B2
· Wu et al.
· 2012
[cited by applicant]
US 8324208B2
· Duffy et al.
· 2012
[cited by applicant]
US 8324405B2
· Ho et al.
· 2012
[cited by applicant]
US 8343952B2
· Kawamoto et al.
· 2013
[cited by applicant]
US 8389520B2
· Thede et al.
· 2013
[cited by applicant]
US 8512972B2
· Evdokimov et al.
· 2013
[cited by applicant]
US 8530404B2
· Seeley et al.
· 2013
[cited by applicant]
US 8598210B2
· Kawamoto et al.
· 2013
[cited by applicant]
US 8703795B2
· Turtle et al.
· 2014
[cited by applicant]
US 8722895B2
· Kawamoto et al.
· 2014
[cited by applicant]
US 8759345B2
· Hocutt et al.
· 2014
[cited by applicant]
US 8796263B2
· Rabinowitz et al.
· 2014
[cited by applicant]
US 8865748B2
· Shalwitz et al.
· 2014
[cited by applicant]
US 8883823B2
· Witschi et al.
· 2014
[cited by applicant]
US 8916585B2
· Arend et al.
· 2014
[cited by applicant]
US 8921389B2
· Ng et al.
· 2014
[cited by applicant]
US 8927591B2
· Ho et al.
· 2015
[cited by applicant]
US 8937078B2
· Bembenek et al.
· 2015
[cited by applicant]
US 8940773B2
· Kawamoto et al.
· 2015
[cited by applicant]
US 8952160B2
· Zhou et al.
· 2015
[cited by applicant]
US 9040522B2
· Brown et al.
· 2015
[cited by applicant]
US 9115085B2
· Witschi et al.
· 2015
[cited by applicant]
US 9145366B2
· Lanthier et al.
· 2015
[cited by applicant]
US 9273034B2
· Sepassi et al.
· 2016
[cited by applicant]
US 9394300B2
· Desai et al.
· 2016
[cited by applicant]
US 9598370B2
· Kawamoto et al.
· 2017
[cited by applicant]
US 9701636B2
· Copp et al.
· 2017
[cited by applicant]
US 9776969B2
· Lanthier et al.
· 2017
[cited by applicant]
US 9918977B2
· Witschi et al.
· 2018
[cited by applicant]
US 9987262B2
· Copp et al.
· 2018
[cited by applicant]
US RE47437E
· Kawamoto et al.
· 2019
[cited by applicant]
US 20020049161A1
· Lehmann
· 2002
[cited by applicant]
US 20020192737A1
· Kaelin, Jr. et al.
· 2002
[cited by applicant]
US 20030153503A1
· Klaus et al.
· 2003
[cited by applicant]
US 20030176317A1
· Guenzler-Pukall et al.
· 2003
[cited by applicant]
US 20040235082A1
· Fourney et al.
· 2004
[cited by applicant]
US 20040254215A1
· Arend et al.
· 2004
[cited by applicant]
US 20050043227A1
· Compernolle et al.
· 2005
[cited by applicant]
US 20060142389A1
· Aurell et al.
· 2006
[cited by applicant]
US 20060276477A1
· Klaus et al.
· 2006
[cited by applicant]
US 20070105899A1
· Suzuki et al.
· 2007
[cited by applicant]
US 20070154482A1
· Sukhatme et al.
· 2007
[cited by applicant]
US 20070203174A1
· Klimko et al.
· 2007
[cited by applicant]
US 20070213335A1
· Fitch et al.
· 2007
[cited by applicant]
US 20070298104A1
· Arend et al.
· 2007
[cited by applicant]
US 20070299086A1
· Kawamoto et al.
· 2007
[cited by applicant]
US 20080004309A1
· Deng et al.
· 2008
[cited by applicant]
US 20080124740A1
· Evdokimov et al.
· 2008
[cited by applicant]
US 20080213404A1
· Johnson et al.
· 2008
[cited by applicant]
US 20090011051A1
· Roth et al.
· 2009
[cited by applicant]
US 20090023666A1
· Gardiner et al.
· 2009
[cited by applicant]
US 20090082357A1
· Fitch et al.
· 2009
[cited by applicant]
US 20090176726A1
· Fisher et al.
· 2009
[cited by applicant]
US 20100021423A1
· Brameld et al.
· 2010
[cited by applicant]
US 20100330199A1
· Zhou et al.
· 2010
[cited by applicant]
US 20100331400A1
· Ho et al.
· 2010
[cited by applicant]
US 20110028507A1
· Kim et al.
· 2011
[cited by applicant]
US 20110077267A1
· Mitani et al.
· 2011
[cited by applicant]
US 20110305776A1
· Ho et al.
· 2011
[cited by applicant]
US 20120028950A1
· Haerter et al.
· 2012
[cited by applicant]
US 20120070369A1
· Iliopoulos et al.
· 2012
[cited by applicant]
US 20120282627A1
· Evdokimov et al.
· 2012
[cited by applicant]
US 20120309977A1
· Lanthier et al.
· 2012
[cited by applicant]
US 20120316204A1
· Shalwitz et al.
· 2012
[cited by applicant]
US 20120329836A1
· Marsh et al.
· 2012
[cited by applicant]
US 20130022974A1
· Chinnaiyan et al.
· 2013
[cited by applicant]
US 20130085121A1
· Wang et al.
· 2013
[cited by applicant]
US 20130123345A1
· Davis
· 2013
[cited by applicant]
US 20130150325A1
· Haerter et al.
· 2013
[cited by applicant]
US 20130196964A1
· Haerter et al.
· 2013
[cited by applicant]
US 20140024675A1
· Witschi et al.
· 2014
[cited by applicant]
US 20140024676A1
· Witschi et al.
· 2014
[cited by applicant]
US 20140045899A1
· Kawamoto et al.
· 2014
[cited by applicant]
US 20140057892A1
· Kawamoto et al.
· 2014
[cited by applicant]
US 20140088101A1
· Ng et al.
· 2014
[cited by applicant]
US 20140171465A1
· Yu
· 2014
[cited by applicant]
US 20140329797A1
· Härter et al.
· 2014
[cited by applicant]
US 20150119425A1
· Kawamoto et al.
· 2015
[cited by applicant]
US 20150141467A1
· Copp et al.
· 2015
[cited by applicant]
US 20150361043A1
· Lanthier et al.
· 2015
[cited by applicant]
US 20160009648A1
· Kawamoto et al.
· 2016
[cited by applicant]
US 20160145254A1
· Mitani et al.
· 2016
[cited by applicant]
US 20160199434A1
· Eubank et al.
· 2016
[cited by applicant]
US 20160214939A1
· Hanselmann et al.
· 2016
[cited by applicant]
US 20160339005A1
· Shalwitz et al.
· 2016
[cited by applicant]
US 20170189387A1
· Kawamoto et al.
· 2017
[cited by applicant]
US 20170260226A1
· Bothe et al.
· 2017
[cited by applicant]
US 20170362178A1
· Lanthier et al.
· 2017
[cited by applicant]
US 20180065933A1
· Hanselmann et al.
· 2018
[cited by applicant]
US 20200017492A1
· Mitani et al.
· 2020
[cited by applicant]
US 20200368223A1
· King
· 2020
[cited by applicant]
US 20230144457A1
· Burke et al.
· 2023
[cited by applicant]
AU 2007265460B2
· 2011
[cited by applicant]
AU 2016243700B2
· 2020
[cited by applicant]
CA 2098158A1
· 1993
[cited by applicant]
CA 2253282A1
· 1997
[cited by applicant]
CA 2659682A1
· 2008
[cited by applicant]
CN 101506149A
· 2009
[cited by applicant]
CN 103429239A
· 2013
[cited by applicant]
CN 111662389A
· 2020
[cited by applicant]
EP 0650960A1
· 1995
[cited by applicant]
EP 0650961A1
· 1995
[cited by applicant]
EP 2044005B1
· 2010
[cited by applicant]
EP 1738751B1
· 2011
[cited by applicant]
EP 2455381A1
· 2012
[cited by applicant]
EP 2951159B1
· 2018
[cited by applicant]
EP 3613742A1
· 2020
[cited by applicant]
EP 3277270B1
· 2021
[cited by applicant]
ES 8800158A1
· 1987
[cited by applicant]
GB 2163746A
· 1986
[cited by applicant]
GB 2444904A
· 2008
[cited by applicant]
JP S6160657A
· 1986
[cited by applicant]
JP H09221476
· 1997
[cited by applicant]
JP H11512414
· 1999
[cited by applicant]
JP 2001048786A
· 2001
[cited by applicant]
JP 2003527424A
· 2003
[cited by applicant]
JP 2007194072A
· 2007
[cited by applicant]
JP 2008201711A
· 2008
[cited by applicant]
JP 2010527378A
· 2010
[cited by applicant]
KR 1020100020893A
· 2010
[cited by applicant]
WO WO1996022021A1
· 1996
[cited by applicant]
WO WO1997041103A1
· 1997
[cited by applicant]
WO WO1997044333A1
· 1997
[cited by applicant]
WO WO1999048870A1
· 1999
[cited by applicant]
WO WO1999063970A1
· 1999
[cited by applicant]
WO WO2001070225A2
· 2001
[cited by applicant]
WO WO2002074980A2
· 2002
[cited by applicant]
WO WO2002074981A2
· 2002
[cited by applicant]
WO WO2002083688A1
· 2002
[cited by applicant]
WO WO2003028663A2
· 2003
[cited by applicant]
WO WO2003032972A1
· 2003
[cited by applicant]
WO WO2003049686A2
· 2003
[cited by applicant]
WO WO2003053997A2
· 2003
[cited by applicant]
WO WO2003097040A1
· 2003
[cited by applicant]
WO WO2004019868A2
· 2004
[cited by applicant]
WO WO2004035812A2
· 2004
[cited by applicant]
WO WO2004048383A1
· 2004
[cited by applicant]
WO WO2004108121A1
· 2004
[cited by applicant]
WO WO2005007192A2
· 2005
[cited by applicant]
WO WO2005115984A2
· 2005
[cited by applicant]
WO WO2005118836A2
· 2005
[cited by applicant]
WO WO2006019831A1
· 2006
[cited by applicant]
WO WO2006030977A2
· 2006
[cited by applicant]
WO WO2006114213A1
· 2006
[cited by applicant]
WO WO2006138511A2
· 2006
[cited by applicant]
WO WO2007031933A2
· 2007
[cited by applicant]
WO WO2007038571A2
· 2007
[cited by applicant]
WO WO2007047194A2
· 2007
[cited by applicant]
WO WO2007070359A2
· 2007
[cited by applicant]
WO WO2007082899A1
· 2007
[cited by applicant]
WO WO2007084667A2
· 2007
[cited by applicant]
WO WO2007088571A2
· 2007
[cited by applicant]
WO WO2007103905A2
· 2007
[cited by applicant]
WO WO2007128495A2
· 2007
[cited by applicant]
WO WO2007136990A2
· 2007
[cited by applicant]
WO WO2007150011A2
· 2007
[cited by applicant]
WO WO2008002576A2
· 2008
[cited by applicant]
WO WO2008043167A1
· 2008
[cited by applicant]
WO WO2008089051A1
· 2008
[cited by applicant]
WO WO2008089052A2
· 2008
[cited by applicant]
WO WO2008130508A1
· 2008
[cited by applicant]
WO WO2008130527A1
· 2008
[cited by applicant]
WO WO2008137060A1
· 2008
[cited by applicant]
WO WO2008141731A2
· 2008
[cited by applicant]
WO WO2008144266A1
· 2008
[cited by applicant]
WO WO2009019656A1
· 2009
[cited by applicant]
WO WO2009020119A1
· 2009
[cited by applicant]
WO WO2009035534A2
· 2009
[cited by applicant]
WO WO2009037570A2
· 2009
[cited by applicant]
WO WO2009039321A1
· 2009
[cited by applicant]
WO WO2009039323A1
· 2009
[cited by applicant]
WO WO2009043093A1
· 2009
[cited by applicant]
WO WO2009049112A1
· 2009
[cited by applicant]
WO WO2009067790A1
· 2009
[cited by applicant]
WO WO2009070644A1
· 2009
[cited by applicant]
WO WO2009073497A2
· 2009
[cited by applicant]
WO WO2009073669A1
· 2009
[cited by applicant]
WO WO2009086044A1
· 2009
[cited by applicant]
WO WO2009086592A1
· 2009
[cited by applicant]
WO WO2009089547A1
· 2009
[cited by applicant]
WO WO2009111337A1
· 2009
[cited by applicant]
WO WO2010006189A2
· 2010
[cited by applicant]
WO WO2010018458A2
· 2010
[cited by applicant]
WO WO2010029577A2
· 2010
[cited by applicant]
WO WO2010113942A1
· 2010
[cited by applicant]
WO WO2011056725A1
· 2011
[cited by applicant]
WO WO2011057112A1
· 2011
[cited by applicant]
WO WO2011084437A1
· 2011
[cited by applicant]
WO WO2012058325A1
· 2012
[cited by applicant]
WO WO2012170377A1
· 2012
[cited by applicant]
WO WO2012170439A1
· 2012
[cited by applicant]
WO WO2012170442A1
· 2012
[cited by applicant]
WO WO2013013609A1
· 2013
[cited by applicant]
WO WO2013070908A1
· 2013
[cited by applicant]
WO WO2014075692A1
· 2014
[cited by applicant]
WO WO2014168986A1
· 2014
[cited by applicant]
WO WO2014197660A1
· 2014
[cited by applicant]
WO WO2014200773A2
· 2014
[cited by applicant]
WO WO2015023967A2
· 2015
[cited by applicant]
WO WO2015073779A1
· 2015
[cited by applicant]
WO WO2015112831A1
· 2015
[cited by applicant]
WO WO2016118858A1
· 2016
[cited by applicant]
WO WO2016153996A1
· 2016
[cited by applicant]
WO WO2016160668A1
· 2016
[cited by applicant]
WO WO2016161094A1
· 2016
[cited by applicant]
WO WO2018031680A1
· 2018
[cited by applicant]
WO WO2018232227A1
· 2018
[cited by applicant]
WO WO2019028150A1
· 2019
[cited by applicant]
WO WO2019060850A1
· 2019
[cited by applicant]
WO WO2020055687A1
· 2020
[cited by applicant]
WO WO2020072645A1
· 2020
[cited by applicant]
WO WO2021087144A1
· 2021
[cited by applicant]
WO WO2021216530A1
· 2021
[cited by applicant]
WO 2021263281A2
· 2021
[cited by applicant]
WO WO2021257800A1
· 2021
[cited by applicant]
WO WO2022006427A1
· 2022
[cited by applicant]
WO WO2022150621A1
· 2022
[cited by applicant]
WO WO2022150623A1
· 2022
[cited by applicant]
WO 2022179967A1
· 2022
[cited by applicant]
WO WO2022187142A1
· 2022
[cited by applicant]
“42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia”, ClinicalTrials.gov, U.S. National Institutes of Health, Jul. 27, 2011, NCT01381094 (116 pages).
[cited by applicant]
“Akebia closes $41 million series C”, Triathlon Medical Ventures, Jun. 4, 2013, retrieved Dec. 1, 2014 from URL: http://www.tmvp.com/news_Akebia_06042013.html, (2 pages).
[cited by applicant]
“Assessment of Thromboembolic Events with Vadadustat vs. Darbepoetin Alfa for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD”, Abstract: PO0462, Nov. 4, 2021 (2 pages).
[cited by applicant]
“BPT closes $12 million in Series B financing”, Membrane Technology, Oct. 2009, pp. 1,16, retrieved from URL: httpps:/ /www.sciencedirect.com/science/article/11ii/S0958211809701983, (3 pages).
[cited by applicant]
“Comprehensive Safety Profile of Vadadustat from Global Phase 3 Clinical Trials”, Abstract: PO0460, Nov. 2, 2021 (2 pages).
[cited by applicant]
“Handbook of Pharmaceutical Excipients”, Sixth Edition 2009, Edited by Rowe et al., pp. 129-133, 663-666 (9 pages).
[cited by applicant]
“Hippuric Acid Sodium Salt”, Science Lab.com: Chemicals & Laboratory Equipment, retrieved Mar. 11, 2010 from URL: http://web.archive.org/web/20041107121553/http://sciencelab.com/page/S/PVAR/10415/SLH2620, (1 page).
[cited by applicant]
“Iron-Related Outcomes in Patients with Dialysis-Dependent CKD Randomized to Vadadustal vs. Darbepoetin Alfa”, Abstract: PO0457, Nov. 4, 2021 (2 pages).
[cited by applicant]
“Iron-Related Outcomes in Patients with Non-Dialysis-Dependent CKD Randomized to Vadadustat vs Darbepoetin Alfa”, Abstract: PO0482, Nov. 4, 2022 (2 pages).
[cited by applicant]
“SCHEMBL3484399”, PubChem, National Center for Biotechnology Information, CID 49848485, Jan. 31, 2011, retrieved Mar. 15, 2016 from URL: https://pubchem.ncbi.nlm.nih.gov/compound/49848485, (13 pages).
[cited by applicant]
“Thromboembolic Events with Vadadustat vs Darbepoetin Alfa for Anemia Treatment in Patients with Dialysis-Dependent CKD”, Abstract: PO0463, Nov. 4, 2022 (2 pages).
[cited by applicant]
“Vadadustat for Treatment of Anemia in Patients with Dialysis-Dependent CKD Receiving Peritoneal Dialysis”, Abstract: PO0464, Nov. 4, 2021 (2 pages).
[cited by applicant]
“Vadadustat”, Wikipedia, Nov. 2, 2018, retrieved Jun. 4, 2019 from URL: https://en.wikipedia.org/wiki/Vadadustat (2 pages).
[cited by applicant]
“Vadadustat, an Oral HIF-PHI, Is Not Associated with Increased Risk of Neoplasm in Patients with Anemia due to CKD”, Abstract: PO0461, Nov. 4, 2021 (2 pages).
[cited by applicant]
“Vadadustat”, PubChem Compound Summary for CID 23634441, National Center for Biotechnology Information, 2022, retrieved Sep. 14, 2022 from URL: https://pubchemncbi.nirn.nih.aov/comooundVadadustat (1 page).
[cited by applicant]
“XEADCOHJERWFOI-UHFFFAOYSA-M”, PubChem, National Center for Biotechnology Information, CID 71491828, Jun. 10, 2013, retrieved Mar. 21, 2016 from URL: https://pubchem.ncbi.nlm.nih.gov/compound/71491828, (12 pages).
[cited by applicant]
“Akebia Announces Positive Top-Line Results from its Phase 2 Study of Vadadustat in Dialysis Patients with Anemia Related Chronic Kidney Disease”, Press Release, Akebia Therapeutics, Inc., Sep. 8, 2015 (4 pages).
[cited by applicant]
“Akebia Announces Presentation of Results from its Phase 2b Study of AKB-6548 in Non-Dialysis Patients with Anemia Related to Chronic Kidney Disease at the International Society of Nephrology's World Congress of Nephrol…
[cited by applicant]
“Akebia Annual Report 2014”, Akebia Annual Report for the fiscal year ended Dec. 31, 2014 (136 pages).
[cited by applicant]
“Akebia Therapeutics Announces Presentation of Clinical Data at Kidney Week 2011”, Press Release, Akebia Therapeutics, Inc., Nov. 15, 2011 (2 pages).
[cited by applicant]
“International Nonproprietary Names for Pharmaceutical Substances (INN)”, WHO Drug Information, vol. 29, No. 4, 2015, (100 pages).
[cited by applicant]
Acker et al., “Genetic evidence for a tumor suppressor role of HIF-2α”, Cancer Cell, vol. 8, No. 2, Aug. 2005, pp. 131-141, DOI: 10.1016/j.ccr.2005.07.003, (11 page).
[cited by applicant]
Alesso et al., “Improving resins for solid phase synthesis: incorporation of 1-[2-(2-methoxyethoxy)ethoxy]-4-vinyl-benzene”, Tetrahedron, vol. 59, No. 36, Sep. 1, 2003, pp. 7163-7169, DOI: 10.1016/S0040-4020(03)01100-1,…
[cited by applicant]
Altschul et al., “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs”, Nucleic Acids Research, vol. 25, No. 17, Sep. 1, 1997, pp. 3389-3402, DOI: 10.1093/nar/25.17.3389, (14 pages).
[cited by applicant]
American Diabetes Association, “Standards of Medical Care in Diabetes-2006”, Diabetes Care, vol. 29, Suppl. 1, Jan. 2006, pp. S4-S42, (39 pages).
[cited by applicant]
Anderson et al., “Antileukemic Activity of Derivatives of 1,2-dimethyl-3,4-bis(hydroxymethyl)-5-phenylpyrrole Bis(N-methylcarbamate)”, Journal of Medicinal Chemistry, vol. 22, No. 8, 1979, pp. 977-980, DOI: 10.1021/jm00…
[cited by applicant]
Anderson, Neal, “Chapter 12—Crystallization and Purification”, Practical Process Research and Development (Second Edition), 2012, pp. 329-364, DOI: 10.1016/B978-0-12-386537-3.00012-5, (38 pages).
[cited by applicant]
Annex et al., “Growth factor-induced therapeutic angiogenesis in the heart: protein therapy”, Cardiovascular Research, vol. 65, No. 3, Feb. 2005, pp. 649-655, DOI: 10.1016/j.cardiores.2004.09.004, (7 pages).
[cited by applicant]
Appelhoff et al., “Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor”, Journal of Biological Chemistry, vol. 279, No. 37, Sep. 2004, DOI: 10.1074/jbc.M40…
[cited by applicant]
Ardelt et al., “Estradiol Regulates Angiopoietin-1 mRNA Expression Through Estrogen Receptor-α in a Rodent Experimental Stroke Model”, Stroke, vol. 36, No. 2, Feb. 2005, pp. 337-341, DOI: 10.1161/01.STR.0000153795.38388…
[cited by applicant]
Aspden et al., “Preventing Medical Errors”, Institute of Medicine of the National Academies, 2007, (481 pages).
[cited by applicant]
Auerbach et al., “Angiogenesis Assays: A Critical Overview”, Clinical Chemistry, vol. 49, No. 1, 2003, pp. 32-40, DOI: 10.1373/49.1.32, (9 pages).
[cited by applicant]
Bao et al., “Chronic Inhibition of Hypoxia-inducible Factor Prolyl 4-hydroxylase Improves Ventricular Performance, Remodeling, and Vascularity After Myocardial Infarction in the Rat”, Journal of Cardiovascular Pharmacol…
[cited by applicant]
Barany et al., “Solid-phase peptide synthesis: a silver anniversary report”, Chemical Biology & Drug Design, vol. 30, No. 6, 1987, pp. 705-739, DOI: 10.1111/j.1399-3011.1987.tb03385.x, (35 pages).
[cited by applicant]
Bartlett et al., “CAVEAT: a program to facilitate the design of organic molecules”, Molecular Recognition in Chemical and Biological Problems, Special Pub., Royal Society of Chemistry, 1989, pp. 182-196 (15 pages).
[cited by applicant]
Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, vol. 66, No. 1, Jan. 1977, pp. 1-19, DOI: 10.1002/jps.2600660104, (19 pages).
[cited by applicant]
Besarab et al., “Evaluation of hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for hemoglobin correction and maintenance in nondialysis chronic kidney disease patients for 16 and 24 weeks”, Nephrology Dial…
[cited by applicant]
Beuck et al., “Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis”, Drug Testing and Analysis, vol. 4, 2012, pp. 830-845, DOI: 10.10…
[cited by applicant]
Böhm, Hans-Joachim, “The computer program LUDI: A new method for the de novo design of enzyme inhibitors”, Journal of Computer-Aided Molecular Design, vol. 6, No. 1, 1992, pp. 61-78, DOI: 10.1007/BF00124387, (18 pages).
[cited by applicant]
Bolhuis et al., “Polyols as filler-binders for disintegrating tablets prepared by direct compaction”, Drug Development and Industrial Pharmacy, vol. 35, No. 6, 2009, pp. 671-677, DOI: 10.1080/03639040802587799 (7 pages).
[cited by applicant]
Branden et al., Introduction to Protein Structure, Second Edition, Garland Science, 1998, pp. 374-375, (4 pages).
[cited by applicant]
Brittain et al., Polymorphism in Pharmaceutical Solids, Second Edition, Drugs and Pharmaceutical Sciences, vol. 192, 2009, pp. 333-335, (7 pages).
[cited by applicant]
Buch et al., “Dose Exposure Relationship of AKB-6548 Is Independent of the Level of Renal Function”, Journal of the American Society of Nephrology, vol. 26, Abstract Edition, Nov. 2015, Exhibit D (3 pages).
[cited by applicant]
Buch et al., “Dose Exposure Relationship of Vadadustat is Independent of the Level of Renal Function”, Akebia Therapeutics, SA-PO537, Exhibit E, Nov. 2015 (1 page).
[cited by applicant]
Buch et al., “Hemodialysis Has Minimal Impact on the Pharmacokinetics of AKB-6548, a Once-Daily Oral Inhibitor of Hypoxia Inducible Factor Prolyl-Hydroxylases (HIFPHs) for the Treatment of Anemia Related to Chronic Kidn…
[cited by applicant]
Burger, Alfred, “Isosterism and bioisosterism in drug design”, Progress in Drug Research, vol. 37, 1991, pp. 287-371, DOI: 10.1007/978-3-0348-7139-6_7, (85 pages).
[cited by applicant]
Bussolino et al., “Molecular mechanisms of blood vessel formation”, Trends in Biochemical Sciences, vol. 22, No. 7, Jul. 1997, pp. 251-256, DOI: 10.1016/s0968-0004(97)01074-8, (6 pages).
[cited by applicant]
Byrn et al., “Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations”, Pharmaceutical Research, vol. 12, No. 7, 1995, pp. 945-954, DOI: 10.1023/a:1016241927429, (10 pages).
[cited by applicant]
Carey, Francis A., Organic Chemistry, Sixth Edition, McGraw Hill, 2006, Chapter 1, p. 9, Chapter 19, pp. 839-840, and Chapter 27, pp. 1182-1183, (12 pages).
[cited by applicant]
Carrasco, Mercedes “Akebia Announces Vadadustat Efficacy and Safety Data to be Presented at American Society of Nephrology Kidney Week 2021”, Press Release, Akebia Therapeutics, Inc., Oct. 18, 2021 (2 pages).
[cited by applicant]
CAS Registry Nos. 1261813-98-2, 1261613-86-8, and 1261518-21-1, Chemcats, 2011, (2 pages).
[cited by applicant]
Catrina et al., “Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function”, Diabetes, vol. 53, No. 12, 2004, pp. 3226-3232, DOI: 10.2337/diabetes.53.12.3226, (7 pages).
[cited by applicant]
Chavan et al., “Pharmacokinetic Evaluation of Drug Interactions Between Vadadustat and HMG-COA Reductase Inhibitors (Statins)”, EMBASE / Elsevier, Jan. 1, 2020, Database Accession No. EMB-633697266, Conference Abstract …
[cited by applicant]
Cheeseright, Tim, “The Identification of Bioisosteres as Drug Development Candidates”, Innovations in Pharmaceutical Technology, 2009, (4 pages).
[cited by applicant]
Cherng, Yie-Jia, “Synthesis of substituted pyridines by the reactions of halopyridines with sulfur, oxygen and carbon nucleophiles under focused microwave irradiation”, Tetrahedron, vol. 58, No. 24, Jun. 10, 2002, pp. 4…
[cited by applicant]
Chertow et al., “Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD”, The New England Journal of Medicine, vol. 384, No. 17, Apr. 29, 2021, pp. 1589-1600, DOI: 10.1056/NEJMoa2035938 (12 pages).
[cited by applicant]
ClinicalTrials.gov, Archive No. NCT01235936, Aug. 30, 2012, retrieved Dec. 1, 2014 from URL: http://clinicaltrials.gov/archive/NCT01235936/2012_09_30, (3 pages).
[cited by applicant]
Cortellis Vadadustat Change History created Mar. 2, 2022 (36 pages).
[cited by applicant]
Costello et al., “Evidence for Changes in RREB-1, ZIP3, and Zinc in the Early Development of Pancreatic Adenocarcinoma”, Journal of Gastrointestinal Cancer, vol. 43, No. 4, 2012, pp. 570-578, DOI: 10.1007/s12029-012-937…
[cited by applicant]
Cousins, Scott W., “Intravitreal Anti-VEGF and Anti-PDGF Combination Therapy”, Retina Today, Oct. 2009, Retrieved from URL: http://retinatoday.com/2009/10/1009_12.php, (2 pages).
[cited by applicant]
Crowley et al., “Drug-Excipient Interactions”, Pharmaceutical Technology Europe, vol. 4, Mar. 2001, pp. 7-12 (6 pages).
[cited by applicant]
Cunliffe et al., “Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analog N-oxaloglycine and its derivatives”, Journal of Medicinal Chemistry, vol. 35, No. 14, 1992, pp. 2652-2658, DOI: 10.1021/j…
[cited by applicant]
Decision of the Technical Board of Appeal of the European Patent Office for Case No. T0777/08 dated May 24, 2011, Retrieved Dec. 19, 2017 from URL: https://www.epo.org/boards-of-appeal/decisions/pdf/t080777ex1.pdf, (17 …
[cited by applicant]
Demetriades et al., “Dynamic Combinatorial Chemistry Employing Boronic Acids/Boronate Esters Leads to Potent Oxygenase Inhibitors” Angewandte Chemie, International Edition , vol. 51, No. 27, Jul. 2, 2012, pp. 6672-6675,…
[cited by applicant]
Designation of Inventor for EP Pat. No. 2044005 dated Jan. 21, 2009 (2 pages).
[cited by applicant]
Donkin et al., “A Substance P Antagonist Reduces Axonal Injury and Improves Neurologic Outcome When Administered Up to 12 Hours after Traumatic Brain Injury”, Journal of Neurotrauma, vol. 28, Feb. 2011, pp. 217-224, DOI…
[cited by applicant]
Donkin et al., “Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury”, Journal of Cerebral Blood Flow & Metabolism, 2009, pp. 1-11, DOI: 10.1038/jcbfm.2009.6…
[cited by applicant]
Dranoff, Glenn, “GM-CSF-secreting melanoma vaccines”, Oncogene, vol. 22, 2003, pp. 3188-3192, DOI: 10.1038/sj.onc.1206459, (5 pages).
[cited by applicant]
Eckardt et al., “Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis”, The New England Journal of Medicine, vol. 384, 2021, pp. 1601-1612, DOI: 10.1056/NEJMoa2025956, (12 pages).
[cited by applicant]
Eckle et al., “HIF1A Reduces Acute Lung Injury by Optimizing Carbohydrate Metabolism in the Alveolar Epithelium”, PLOS Biology, vol. 11, No. 9, 2013, pp. e1001665, DOI: 10.1371/journal.pbio.1001665, (25 pages).
[cited by applicant]
Elson et al., “Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α”, Genes & Development, vol. 15, 2001, pp. 2520-2532, DOI: 10.1101/gad.914801, (1…
[cited by applicant]
Elvidge et al., “Concordant Regulation of Gene Expression by Hypoxia and 2-Oxoglutarate-dependent Dioxygenase Inhibition”, Journal of Biological Chemistry, vol. 281, No. 22, Jun. 2006, pp. 15215-15226, DOI: 10.1074/jbc.…
[cited by applicant]
Enoch et al., “ABC of wound healing: Non-surgical and drug treatments”, BMJ, vol. 332, No. 7546, 2006, pp. 900-903, DOI: 10.1074/jbc.M511408200, (4 pages).
[cited by applicant]
Exhibit A, “2009 Pat. App. LEXIS 10905”, Board of Patent Appeals and Interferences, Mar. 11, 2009, Decided, Ex parte Thomas G. Xydis (5 pages).
[cited by applicant]
Exhibit B, “2015 Pat. App. LEXIS 435”, Patent Trial and Appeal Board, Jan. 27, 2015, Decided, Ex parte Christine Esau and Eric E. Swayze (9 pages).
[cited by applicant]
Exhibit C: Lee et al., “6.1 Pharmaceutical Preformulation: Physicochemical Properties of Excipients and Powders and Tablet Characterization”, Pharmaceutical Manufacturing Handbook: Production and Processes, 2008, pp. 88…
[cited by applicant]
Exhibit D: Perumal et al., “6.2 Role of Preformulation in Development of Solid Dosage Forms”, Pharmaceutical Manufacturing Handbook: Production and Processes, 2008, pp. 933-975, (45 pages).
[cited by applicant]
Exhibit E: Cavatur et al., “Chapter 14—Preformulation Studies for Tablet Formulation Development”, Pharmaceutical Dosage Forms—Tablets: Unit Operation and Mechanical Properties, 2008, pp. 465-483, (20 pages).
[cited by applicant]
Exhibit F:
[cited by applicant]
Exhibit G:
[cited by applicant]
Extended European Search Report for EP Application No. 11000872.9 dated Apr. 28, 2011 (8 pages).
[cited by applicant]
Extract from USPTO Patent Assignment Database for U.S. Appl. No. 11/821,936, retrieved on Feb. 4, 2013 (1 page).
[cited by applicant]
Favier et al., “HIF2α reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma”, BMC Cancer, vol. 7, Article No. 139, 2007, DOI: 10.1186/1471-2407-7-139, (10 pages).
[cited by applicant]
Felton et al., “An update on pharmaceutical film coating for drug delivery”, Expert Opinion on Drug Delivery, vol. 10, No. 4, 2013, pp. 421-435, DOI: 10.1517/17425247.2013.763792, (15 pages).
[cited by applicant]
Felton, “Film Coating of Oral Solid Dosage Forms”, Encyclopedia of Pharmaceutical Technology, 2007, pp. 1729-1747, (18 pages).
[cited by applicant]
Fiedler Lexikon de Hilfsstoffe für Pharmazie, Kosmetik und angrenzende Gebiete, Fifth Edition, 2002, vol. 9, pp. 1248, (3 pages).
[cited by applicant]
Flower et al., “Modelling G-protein-coupled receptors for drug design”, Biochimica et Biophysica Acta (BBA)—Reviews on Biomembranes, vol. 1422, No. 3, Nov. 16, 1999, pp. 207-234, DOI: 10.1016/s0304-4157(99)00006-4, (28 …
[cited by applicant]
Folkman, Judah, “Chapter 10—Tumor Angiogenesis”, The Molecular Basis of Cancer, 1995, pp. 206-232, (29 pages).
[cited by applicant]
Franklin et al., “Approaches to the design of anti-fibrotic drugs”, Biochemical Society Transactions, vol. 19, No. 4, Nov. 1991, pp. 812-815, DOI: 10.1042/bst0190812, (4 pages).
[cited by applicant]
Gaunt et al., “Rational Design of Benzyl-Type Protecting Groups Allows Sequential Deprotection of Hydroxyl Groups by Catalytic Hydrogenolysis”, Journal of Organic Chemistry, vol. 63, No. 13, 1998, pp. 4172-4173, DOI: 10…
[cited by applicant]
Gaunt et al., “Rational Design of Benzyl-Type Protecting Groups Allows Sequential Deprotection of Hydroxyl Groups by Catalytic Hydrogenolysis”, Journal of Organic Chemistry, vol. 63, No. 13, 1998, pp. 4172-4173, DOI: 10…
[cited by applicant]
Gavhane et al., “Solid Tumors: Facts, Challenges and Solutions”, International Journal of Pharma Sciences and Research, vol. 2, No. 1, 2011, pp. 1-12, (12 pages).
[cited by applicant]
Goodford, P. J., “A computational procedure for determining energetically favorable binding sites on biologically important macromolecules”, Journal of Medicinal Chemistry, vol. 28, No. 7, 1985, pp. 849-857, DOI: 10.102…
[cited by applicant]
Goodsell et al., “Automated docking of substrates to proteins by simulated annealing”, Proteins, vol. 8, No. 3, 1990, pp. 195-202, DOI: 10.1002/prot.340080302, (8 pages).
[cited by applicant]
Greer et al., “The updated biology of hypoxia-inducible factor”, The EMBO Journal, vol. 31, No. 11, May 30, 2012, pp. 2448-2460, DOI: 10.1038/emboj.2012.125, (13 pages).
[cited by applicant]
Guillory et al., “Generation of Polymorphs, Hydrates, Solvates, and Amorphous Solids”, Polymorphism in Pharmaceutical Solids, vol. 95, 1999, pp. 183-226, (46 pages).
[cited by applicant]
Haase et al., “Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents”, Nephrology Dialysis Transplantation, vol. 34, No. 1, Jan. …
[cited by applicant]
Hardcastle et al., “Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach”, Journal of Medicinal Chemistry, vol. 48, No. 24, 2005, pp. 7829-784…
[cited by applicant]
Hartman et al., “Controlled Hemoglobin Response in a Double-Blind, Placebo-Controlled Trial of AKB-6548 in Subjects with Chronic Kidney Disease”, Nephrology Dialysis Transplantation, vol. 29, Supplement No. 3, May 2014,…
[cited by applicant]
Haywood et al., “Pharmaceutical excipients—where do we begin?”, Australian Prescriber, vol. 34, Aug. 2011, pp. 112-114 (3 pages).
[cited by applicant]
Hoeksema et al., “Structure of rubradirin”, Journal of the American Chemical Society, vol. 104, No. 19, 1982, pp. 5173-5181, DOI: 10.1021/ja00383a030, (9 pages).
[cited by applicant]
Hu et al., “Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation”, Molecular and Cellular Biology, vol. 23, No. 24, 2003, pp. 9361-9374, DOI: 10.1128/MCB.23.24.9361-9374.2003,…
[cited by applicant]
Ingersoll et al., “Hippuric Acid”, Organic Synthesis, CV 2, 328, Retrieved on Mar. 11, 2010 from the Internet at <http://web.archive.org/web/20020724135719/http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2p03…
[cited by applicant]
Interlocutory Decision in Opposition Proceedings for EP Pat. No. 2044005 dated May 3, 2013 (76 pages).
[cited by applicant]
International Preliminary Report on Patentability, Ch. I, for PCT/US2012/040833 dated Dec. 27, 2013 (7 pages).
[cited by applicant]
International Preliminary Report on Patentability, Ch. I, for PCT/US2021/028126 dated Nov. 3, 2022 (14 pages).
[cited by applicant]
International Search Report and Written Opinion for PCT/US2007/014832 dated May 8, 2008 (9 pages).
[cited by applicant]
International Search Report and Written Opinion for PCT/US2012/040833 dated Aug. 29, 2012 (9 pages).
[cited by applicant]
International Search Report and Written Opinion for PCT/US2014/040889 dated Dec. 31, 2014 (20 pages).
[cited by applicant]
International Search Report and Written Opinion for PCT/US2015/012634 dated Apr. 20, 2015 (9 pages).
[cited by applicant]