IP Library › Granted Patent US 12,478,615
Granted Patent B2
US 12,478,615 · App. 18/537,481 · Granted Nov 25, 2025

Prolyl hydroxylase inhibitors and methods of use

Inventors: Richard Masaru Kawamoto (Divide, CO); Shengde Wu (West Chester, OH); Artem G. Evdokimov (Foristell, MO); Kenneth D. Greis (Fort Thomas, KY); Angelique Sun Boyer (West Chester, OH); Namal C. Warshakoon (Cary, NC)
Assignee: Akebia Therapeutics, Inc.
A61K31/4418A61K31/4433C07C235/60C07C237/42C07C255/57C07D213/65C07D213/81C07D295/192C07D401/04C07D401/10C07D405/04C07D405/10C07D417/04Y02A50/30
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 12,478,615
App. No.
18/537,481
Granted
Nov 25, 2025
Kind
B2
Abstract

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia.

Claims (20)

1 . A process for preparing a compound having the formula:

comprising:

(a) reacting a 4-iodo-picolinic acid:

with a glycine methyl ester hydrochloride:

in the presence of coupling agents to form [(4-iodo-pyridine-2-carbonyl)-amino]-acetic acid methyl ester:

 and

(b) reacting the [(4-iodo-pyridine-2-carbonyl)-amino]-acetic acid methyl ester obtained from step (a) with a 4-methylphenyl boronic acid:

in the presence of a catalyst to form [(4-(4-methylphenyl)pyridine-2-carbonyl)amino]-acetic acid methyl ester:

2 . The process of claim 1 , further comprising reacting [(4-(4-methylphenyl)pyridine-2-carbonyl)amino]-acetic acid methyl ester:

with a base to form [(4-(4-methylphenyl)pyridine-2-carbonyl)amino]-acetic acid:

3 . The process of claim 1 , wherein the coupling agents in step (a) are 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) and 1-hydroxybenzotriazole (HOBt).

4 . The process of claim 1 , wherein the catalyst in step (b) is [1,1′-bis (diphenylphosphino)ferrocine]dichloro palladium (II).

5 . The process of claim 1 , wherein the reaction in step (b) is conducted in the presence of a base that is K 3 PO 4 .

6 . The process of claim 2 , wherein the base that is LiOH.

7 . A compound having the formula:

or a pharmaceutically acceptable salt thereof.

8 . A pharmaceutical composition comprising:

(1) a pharmaceutically acceptable excipient, and

(2) a compound having the formula:

or a pharmaceutically acceptable salt thereof.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 25, 2024
From: WARNER CHILCOTT COMPANY, LLC
To: AKEBIA THERAPEUTICS, INC.
Reel/Frame 068078/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 25, 2024
From: WU, SHENGDE; WARSHAKOON, NAMAL C.; EVDOKIMOV, ARTEM G.; GREIS, KENNETH D.; BOYER, ANGELIQUE SUN
To: THE PROCTER & GAMBLE COMPANY
Reel/Frame 068078/0017 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 25, 2024
From: KAWAMOTO, RICHARD MASARU
To: THE PROCTER & GAMBLE COMPANY
Reel/Frame 068078/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 25, 2024
From: THE PROCTER & GAMBLE COMPANY
To: WARNER CHILCOTT COMPANY, LLC
Reel/Frame 068146/0503 →
SECURITY INTEREST Recorded Jan 29, 2024
From: AKEBIA THERAPEUTICS, INC.; KERYX BIOPHARMACEUTICALS, INC.
To: KREOS CAPITAL VII (UK) LIMITED
Reel/Frame 066377/0654 →
Continuity (12)
Continuation 17815391 · Jul 27, 2022
Continuation 16908092 · Jun 22, 2020
Continuation 16119146 · Aug 31, 2018
Continuation 15420617 · Jan 31, 2017
Continuation 14854080 · Sep 15, 2015
Continuation 14568200 · Dec 12, 2014
Continuation 14062011 · Oct 24, 2013
Division 13681876 · Nov 20, 2012
Continuation 12860073 · Aug 20, 2010
Continuation 11821936 · Jun 26, 2007
Provisional Application 60816522 · Jun 26, 2006
Related Publication 20240358691A1 · Oct 31, 2024
References Cited (260)
US 3894920A · Kondo et al. · 1975 [cited by applicant]
US 4016287A · Ebhardt et al. · 1977 [cited by applicant]
US 4044049A · Ruyle et al. · 1977 [cited by applicant]
US 5397799A · Kress et al. · 1995 [cited by applicant]
US 5405613A · Rowland et al. · 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 5643957A · Leone-Bay 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 · Wiedmann et al. · 2000 [cited by applicant]
US 6093730A · Weidmann et al. · 2000 [cited by applicant]
US 6323227B1 · Klein et al. · 2001 [cited by applicant]
US 6420427B1 · Takahashi et al. · 2002 [cited by applicant]
US 6566088B1 · McKnight et al. · 2003 [cited by applicant]
US 6589758B1 · Zhu et al. · 2003 [cited by applicant]
US 6855510B2 · Kaelin et al. · 2005 [cited by applicant]
US 7183287B2 · Durley 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 7588824B2 · Wudl et al. · 2009 [cited by applicant]
US 7588924B2 · Evdokimov et al. · 2009 [cited by applicant]
US 7618940B2 · Fourney et al. · 2009 [cited by applicant]
US 7811595B2 · Kawamoto et al. · 2010 [cited by applicant]
US 7897612B2 · Fitch 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 8323671B2 · Wu et al. · 2012 [cited by applicant]
US 8343952B2 · Kawamoto 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 8722895B2 · Kawamoto et al. · 2014 [cited by applicant]
US 8865748B2 · Shalwitz et al. · 2014 [cited by applicant]
US 8940773B2 · Kawamoto et al. · 2015 [cited by applicant]
US 9145366B2 · Lanthier et al. · 2015 [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 9987262B2 · Copp et al. · 2018 [cited by applicant]
US 10149842B2 · Copp et al. · 2018 [cited by applicant]
US 10150734B2 · Hanselmann et al. · 2018 [cited by applicant]
US 10246416B2 · Lanthier et al. · 2019 [cited by applicant]
US 10596158B2 · Copp et al. · 2020 [cited by applicant]
US 10729681B2 · Kawamoto et al. · 2020 [cited by applicant]
US 10738010B2 · Lanthier et al. · 2020 [cited by applicant]
US 11065237B2 · Copp et al. · 2021 [cited by applicant]
US 11267785B2 · Lanthier et al. · 2022 [cited by applicant]
US 11426393B2 · Kawamoto et al. · 2022 [cited by applicant]
US 11883386B2 · Kawamoto et al. · 2024 [cited by applicant]
US 20030153503A1 · Klaus et al. · 2003 [cited by applicant]
US 20030176317A1 · Guenzler-Pukall et al. · 2003 [cited by applicant]
US 20040146964A1 · Maxwell et al. · 2004 [cited by applicant]
US 20040254215A1 · Arend et al. · 2004 [cited by applicant]
US 20060276477A1 · Klaus et al. · 2006 [cited by applicant]
US 20070154482A1 · Sukhatme et al. · 2007 [cited by applicant]
US 20070213335A1 · Fitch et al. · 2007 [cited by applicant]
US 20080213404A1 · Johnson et al. · 2008 [cited by applicant]
US 20100331303A1 · Kawamoto et al. · 2010 [cited by applicant]
US 20100331374A1 · Wu et al. · 2010 [cited by applicant]
US 20120316204A1 · Shalwitz et al. · 2012 [cited by applicant]
US 20120329836A1 · Marsh et al. · 2012 [cited by applicant]
US 20130203816A1 · Kawamoto et al. · 2013 [cited by applicant]
US 20130245076A1 · Kawamoto et al. · 2013 [cited by applicant]
US 20140045899A1 · Kawamoto et al. · 2014 [cited by applicant]
US 20140057892A1 · Kawamoto et al. · 2014 [cited by applicant]
US 20150119425A1 · Kawamoto et al. · 2015 [cited by applicant]
US 20160009648A1 · Kawamoto et al. · 2016 [cited by applicant]
US 20160143891A1 · Shalwitz 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 20170258773A1 · Copp et al. · 2017 [cited by applicant]
US 20180065933A1 · Hanselmann et al. · 2018 [cited by applicant]
US 20180092892A1 · Smith et al. · 2018 [cited by applicant]
US 20190375713A1 · Lanthier et al. · 2019 [cited by applicant]
US 20200345711A1 · Copp et al. · 2020 [cited by applicant]
US 20210070709A1 · Gorin et al. · 2021 [cited by applicant]
US 20210122715A1 · Lanthier et al. · 2021 [cited by applicant]
US 20210206721A1 · Ranjan et al. · 2021 [cited by applicant]
US 20220040159A1 · Copp et al. · 2022 [cited by applicant]
CA 2098158A1 · 1993 [cited by applicant]
CA 2253282A1 · 1997 [cited by applicant]
CN 111320577A · 2020 [cited by applicant]
EP 0650960A1 · 1995 [cited by applicant]
EP 0650961A1 · 1995 [cited by applicant]
EP 0650960B1 · 1997 [cited by applicant]
EP 0650961B1 · 1997 [cited by applicant]
EP 2044005B1 · 2010 [cited by applicant]
JP H09221476A · 1997 [cited by applicant]
JP 2001048786A · 2001 [cited by applicant]
JP 2006316054A · 2006 [cited by applicant]
WO WO1997041103A1 · 1997 [cited by applicant]
WO WO1997044333A1 · 1997 [cited by applicant]
WO WO1999000356A1 · 1999 [cited by applicant]
WO WO1999048870A1 · 1999 [cited by applicant]
WO WO2000074725A1 · 2000 [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 WO2003057820A2 · 2003 [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 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 WO2007136990A2 · 2007 [cited by applicant]
WO WO2007150011A2 · 2007 [cited by applicant]
WO WO2008002576A2 · 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 WO2008144266A1 · 2008 [cited by applicant]
WO WO2009019656A1 · 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 WO2012170377A1 · 2012 [cited by applicant]
WO WO2014200773A2 · 2014 [cited by applicant]
WO WO2015073779A1 · 2015 [cited by applicant]
WO WO2016153996A1 · 2016 [cited by applicant]
WO WO2016161094A1 · 2016 [cited by applicant]
WO WO2019028150A1 · 2019 [cited by applicant]
WO WO2019217550A1 · 2019 [cited by applicant]
WO WO2022006427A1 · 2022 [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, 7163-7169, 2003. [cited by applicant]
Altschul et al., Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs, Nucleic Acids Res., vol. 25, No. 27, 3389-3402, 1997. [cited by applicant]
Anderson et al., Antileukemic Activity of Derivatives of 1,2-Dimethyl-3,4-bis(hydroxymethyl)-5-phenylpyrrole Bis(N-methylcarbamate), J. Med. Chem.: vol. 22, No. 8, 977-980, 1979. [cited by applicant]
Annex et al., Growth Factor-Induced Therapeutic Angiogenesis in the Heart: Protein Therapy, Cardiovascular Research, vol. 65, No. 3, 649-655, 2005. [cited by applicant]
Ardelt et al., Estradiol Regulates Angiopoietin-1 mRNA Expression Through Estrogen Receptor-a in a Rodent Experimental Stroke Model, Stroke, vol. 36, 337-341, 2005. [cited by applicant]
Atkinson, G. E. et al., A Versatile Polymer-Supported 4-(4 Methylphenyl(chloro)methyl)phenoxy Linker for Solid-Phase Synthesis of Pseudopeptides, Journal of Organic Chemistry, 2000, vol. 65, No. 16, p. 5048-5056. [cited by applicant]
Auerbach et al., Angiogenesis Assays: A Critical Overview, Clinical Chemistry, vol. 49, 32-40, 2003. [cited by applicant]
Aucella et al., Synergistic effect of desferrioxamine and recombinant erythropeoietin on erythroid precursor proliferation in chronic renal failure, Nephrol. Dial Transplant. May 1999; 14(5):1171-1175. [cited by applicant]
Barany et al., Solid-phase Peptide Synthesis: A Silver Anniversary Report, Int. J. Peptide Protein Res., vol. 30, No. 6, 705-739, 1987. [cited by applicant]
Baringhaus et al., 3D QSAR of prolyl 4-hydroxylase inhibitors, Chapter 23 in “Molecular Modeling and Prediction of Bioactivity” (Springer, Boston, MA), 2000, 345-346. [cited by applicant]
Bartlett et al., Molecular Recognition in Chemical and Biological Problems, Special Pub., Royal Chem. Soc., vol. 78, 182-196 Caveat: A Program to Facilitate the Structure-derived Design of Biologically Active Molecules,… [cited by applicant]
Bohm, The Computer Program LUDI: A New Method for the Novo Design of Enzyme Inhibitors, J. Computer-Aided Molecular Design, vol. 6, 61-78, 1992. [cited by applicant]
Branden et al., Introduction to Protein Structure Second Edition, Garland Publishing, Inc., New York, pp. 374-375, 1999. [cited by applicant]
Burger, Isosterism and bioisosterism in drug design, Progress in Drug Research, vol. 37, 287-371, 1991. [cited by applicant]
Bussolino, Molecular Mechanisms of Blood Vessel Formation, Trends Biochem. Sci., vol. 22, No. 7, 251-256, 1997. [cited by applicant]
Catrina et al., Hyperglycemia Regulates Hypoxia-Inducible Factor-la Protein Stability and Function, Diabetes, vol. 53, 3226-3232, 2004. [cited by applicant]
Cheeseright, The identification of bioisosteres as drug development candidates, Innovations in Pharmaceutical Technology, 22-26, 2009. [cited by applicant]
Cunliffe et al., Novel Inhibitors of Prolyl 4-Hydroxylase. 3. Inhibition by the Substrate Analogue N-Oxaloglycine and Its Derivatives, J. Med. Chem. vol. 35, 2652-2658, 1992. [cited by applicant]
Elson et al., Induction of Hypervascularity Without Leakage or Inflammation in Transgenic Mice Overexpressing Hypoxia-Indicible Factor-la, Genes & Dev., vol. 15, 2520-2532, 2001. [cited by applicant]
Enoch et al., ABC of wound healing: non-surgical and drug treatments, BMJ, vol. 332, 900-903, 2006. [cited by applicant]
Exhibit SW2 to the first report of Simon Ward, filed on behalf of the Claimants in Claim No. HP-2018-000036 and the First and Second Defendants in IL-2019-000031, and the Claimants in Claim No. HP-2018-000032, in the Hi… [cited by applicant]
Flower, Modelling G-protein-coupled receptors for drug design, Biochimica et Biophysica Acta, vol. 1422, 207-234, 1999. [cited by applicant]
Folkman et al., Tumor Angiogenesis, The Molecular Basis of Cancer, Mendelsohn et al., eds., W. B. Saunders, Chapter 10, pp. 206-232, 1995. [cited by applicant]
Franklin et al., Approaches to the Design of Anti-Fibrotic Drugs, Biochem. Soc. Trans., vol. 19, No. 4, :812-5, Nov. 1991. [cited by applicant]
Gavhane et al., Solid tumors: facts, challenges and solutions, International Journal of Pharma Sciences and Research, vol. 2, No. 1, 1-12, 2011. [cited by applicant]
Gaunt et al., Rational design of benzyl-type protecting groups allows sequential deprotection of hydroxyl groups by catalytic hydrogenolysis, J. Org. Chem., vol. 63, 4172-4173, 1998. [cited by applicant]
Goodford, A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules, J. Med. Chem., vol. 28, No. 7, 849-857, 1985. [cited by applicant]
Gunzler et al., Prolyl 4-hydroxylase inhibitors, Chapter 2 in 'Prolyl hydroxylase, protein disulfide isomerase, and other structurally related proteins (Marcel Dekker), 1998, 65-95. [cited by applicant]
Goodsell et al., Automated Docking of Substrates to Proteins by Simulated Annealing, Proteins: Structure, Function, and Genetics, vol. 8, 195-202, 1990. [cited by applicant]
Gupta et al., Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD, Am J Kidney Dis. 2017, vol. 69, issue 6, pp. 815-826. DOI: 10.1053/j.ajkd.2016.12.011 (Yea… [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, J. Med. Chem., vol. 48, 7829-7846, 2005. [cited by applicant]
Hippuric acid sodium salt. Science Lab.com: Chemicals & Laboratory Equipment. (http://web.archive.org/web/20041107121553/http://www.sciencelab.com/page/S/PVAR/10415/SLH2620, accessed Mar. 11, 2010). 1 page. [cited by applicant]
Hirsila et al., Characterization of the Human Prolyl 4-Hyrdoxylases That Modify the Hypoxia-inducible Factor, The Journal of Biological Chemistry, vol. 278, No. 33, 30772-30780, Aug. 2003. [cited by applicant]
Hoeksema et al., Structure of Rubradirin, Journal of American Chemical Society, vol. 104, 5173-5181, 1982. [cited by applicant]
Ikura; Bioorganic & Medicinal Chemistry 14 (2006) 4241-4252. doi: 10.1016/j.bmc.2006.01.059 (Year: 2006). [cited by applicant]
Ingersoll et al., Organic Syntheses, CV 2, 328, “Hippuric acid”. (http://web.archive.org/web/20020724135719/http://www.orgsyn.org/orgsyn/orgysn/prepContent.asp?prep=cv2p0328, accessed Mar. 11, 2010). 4 pages. [cited by applicant]
International Search Report dated May 8, 2008 for PCT/US2007/014832. 3 pages. [cited by applicant]
International Union of Pure and Applied Chemistry; Glossary of Class Names of Organic Compounds and Reactive Intermediates Based on Structure; Pure & D Appl. Chem., vol. 67, Nos. 8/9, 1307-1375, 1995. [cited by applicant]
Ivan et al., Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor, Proceedings of the National Academy of Science; vol. 99, No. 21, 13459-13464, 20… [cited by applicant]
Ivan et al., HIFa Targeted for VHL-Mediated Destruction by Praline Hydroxylation: Implications for 02 Sensing, Science vol. 292, 464-468, 2001. [cited by applicant]
Jaakkola et al., Targeting of HIF-a to the von Rippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation, Science, vol. 292, 468-472, 2001. [cited by applicant]
Jones et al., Molecular Recognition of Receptor Sites Using a Genetic Algorithm with a Description of Desolvation, J. Mol. Biol., vol. 245, 43-53, 1995. [cited by applicant]
Kaelin, Praline Hydroxylation and Gene Expression, Annu. Rev. Biochem., vol. 74, 115-125, 2005. [cited by applicant]
Kawashima et al., Suppressive effect of quinolinic acid and hippuric acid on bone marrow erythroid growth and lymphocyte blast formation in uremia, Advances in Experimental Medicine and Biology, vol. 223, 69-72, 1987. [cited by applicant]
Ke et al., Hypoxia-Inducible Factor-1 (HIF-1), Molecular Pharmacology, vol. 70, No. 5, 1469-1480, Aug. 2006. [cited by applicant]
Kim et al., Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications, Molecules, vol. 20, No. 11, 20551-20568, Nov. 2015. [cited by applicant]
Krantz, “Erythropoietin,” Blood, vol. 77, 419-434, 1991. [cited by applicant]
Kuntz et al., A Geometric Approach to Macromolecule- Ligand Interactions, J. Mol. Biol., vol. 161, 269-288, 1982. [cited by applicant]
Langsetmo, Inhibition of HIF-Prolyl Hydroxylases with FG-4539 Is Neuroprotective in a Mouse Model of Permanent Focal Ischemia, International Stroke Conference, Kissimmee, Florida, Presentation No. 427, 2006. 1 page. [cited by applicant]
Lee et al., Structure of Human FIH-1 Reveals a Unique Active Site Pocket and Interaction Sites for HIF-1 and von Hinnel Lindau, JBC, vol. 278, 7558-7563, 2003. [cited by applicant]
Li et al., PR39, A Peptide Regulator of Angiogenesis, Nat Med., vol. 6, No. 1, 49-55, 2000. [cited by applicant]
Lima et al., Bioisosterism: a useful strategy for molecular modification and drug design, Current Medicinal Chemistry, vol. 12, 23-49, 2005. [cited by applicant]
Mancini et al., Effect of Erythropoietin on Exercise Capacity in Patients with Moderate to Severe Chronic Heart Failure, Circulation, vol. 107, 294-299, 2003. [cited by applicant]
McDonough et al., Cellular Oxygen Sensing: Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2), PNAS, vol. 103 No. 26, 9814-9819, 2006. [cited by applicant]
Miranker et al., Functionality Maps of Binding Sites: A Multiple Copy Simultaneous Search Method, Proteins: Structure, Function and Genetics, vol. 11, 29-34, 1991. [cited by applicant]
Nguyen et al., Cellular Interactions in Vascular Growth and Differentiation, Int. Review of Cytology, vol. 204, 1-48, 2001. [cited by applicant]
Nishibata et al., Automatic Creation of Drug Candidate Structures Based on Receptor Structure. Starting Point for Artificial Lead Generation, Tetrahedron, vol. 47, No. 43, 8985-8990, 1991. [cited by applicant]
Notice of Opposition communication for European Patent No. 3357911, dated Feb. 23, 2023. 26 pages. [cited by applicant]
O'Reilly et al., Angiostatin: A Novel Angiogenesis Inhibitor that Mediates the Suppression of Metastases bv a Lewis Lung Carcinoma, Cell, vol. 79, 315-328, 1994. [cited by applicant]
O'Reilly et al., “Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth,” Cell, 88:277-285 (1997). [cited by applicant]
Pergola et al., Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease, Kidney International, vol. 90, No. 5, 1115-1122, Sep. 2016. [cited by applicant]
Peyssonnaux et al., HIF- la Expression Regulates the Bactericidal Capacity of Phagocytes, J. Clinical Invest., vol. 115, No. 7, 1806-1815, 2005. [cited by applicant]
Piyamongkol et al., Amido-3-hydroxypyridin-4-ones as iron(III) ligands, Chemistry, A European Journal, vol. 16, 6374-6381, 2010. [cited by applicant]
Qian et al., A Randomized, Double-Blind, Placebo Controlled Trial ofFG-4592 for Correction of Anemia in Subjects with Chronic Kidney Disease in China, Oral Abstract FR-ORO11, J. Am. Soc. Nephrol., vol. 24:38A, 2013. 1 p… [cited by applicant]
Rahtu-Korpela, HIF Prolyl 4-Hydroxylase-2 Inhibition Improves Glucose and Lipid Metabolism and Protects Against Obesity and Metabolic Dysfunction, Diabetes, vol. 63, 3324-3333, 2014. [cited by applicant]
Schelhaas et al., Protecting group strategies in organic synthesis, Angew, Chem. Int. Ed. Engl., vol. 35, 2056-2083, 1996. [cited by applicant]
Schoneberg et al., Structural Basis of G Protein-Coupled Receptor Function, Molecular and Cellular Endocrinology, vol. 151, 181-193, 1999. [cited by applicant]
Search Report dated Apr. 28, 2011 for European Pat. App. No. 11000872.9. 3 pages. [cited by applicant]
Semenza, HIF-1 and human disease: one highly involved factor, Genes and Development, vol. 14, No. 16, 1983-1991, Aug. 2000. [cited by applicant]
Semenza et al., Transcriptional Regulation of Genes Encoding Glycolytic Enzymes by Hypoxia-Inducible Factor I , J. Biol. Chem., vol. 269, 23757-23763, 1994. [cited by applicant]
Semenza, Regulation of Erythropoietin Production: New Insights into Molecular Mechanisms of Oxygen Homeostasis, Hematol. Oncol. Clin. North Am., vol. 8, 863-884, 1994. [cited by applicant]
Semenza, Signal Transduction to Hypoxia-inducible Factor I , Biochem. Pharmacol, vol. 64, 993-998, 2002. [cited by applicant]
Sexton, Recent advances in our understanding of peptide hormone receptors and RAMPS, Current Opinion in Drug Discovery and Development, vol. 2, No. 5. 440-448, 1999. [cited by applicant]
Sheehan, 3-Hydroxypicolinic Acid and Some of its Derivatives, J. Organic Chemistry, vol. 31, No. 3, 636-638, 1996. [cited by applicant]
Siddiq et al., Hypoxia-inducible Factor Prolyl 4-Hydroxylase Inhibition, The Journal of Biological Chemistry, vol. 280, No. 50, 41732-41743, Dec. 2005. [cited by applicant]
Silverman, The Organic Chemistry of Drug Design and Drug Action, 2nd Edition, 2004, Elsevier, Section 2.2, E.4, pp. 29-34. [cited by applicant]
Standards of Medical Care in Diabetes-2006, Diabetes Care, vol. 29. 4-s42, 2006. 39 pages. [cited by applicant]
Sutter et al., Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations, PNAS, vol. 97, No. 9, 4748-4753, 2000. [cited by applicant]
Teicher et al., Potentiation of Cytotoxic Cancer Therapies by TNP-470 Alone and with Other Anti-Angiogenic Agents, Int. J. Cancer, vol. 57, 920-925, 1994. [cited by applicant]
Thornber, Isosterism and molecular modification in drug design, Chem Soc. Rev., vol. 8, 563-580, 1979. [cited by applicant]
Tzschucke et al., Fluorous-Silica-Supported Perfluoro-Tagged Palladium Complexes Catalyze Suzuki Coupling in Water, Helvetica Chimica Acta; vol. 87, 2882-2889, 2004. [cited by applicant]
Vickerstaffe et al., Fully Automated Polymer-Assisted Synthesis of 1,5-Biaryl Pyrazoles, J. Comb. Chem., vol. 6, 332-33, 2004. [cited by applicant]
Vincent et al., Angiogenesis is Induced in a Rabbit Model of Hindlimb Ischemia by Naked DNA Encoding an HIF-I aNP16 Hybrid Transcription Factor, Circulation, vol. 102, 2255-2261, 2000. [cited by applicant]
Warnecke et al., Activation of the Hypoxia-Inducible Factor Pathway and Stimulation of Angiogenesis by Application of Prolyl Hydroxylase Inhibitors, FASEB Journal, vol. 17, 1186-1188, 2003. [cited by applicant]
Warshakoon et al., Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors, Bioorganic & Medicinal Chemistry Letters, vol. 16, 5616-5620, 2006. [cited by applicant]
Wax et al., SM-20 is a Novel20-kd Protein Whose Expression in the Arterial Wall is Restricted to Smooth Muscle, Lab. Invest., vol. 74, No. 4, 797-808, 1996. [cited by applicant]
Weidner et al., Tumor Angiogenesis and Metastasis—Correlation in Invasive Breast Carcinoma, New Eng. J. Med., vol. 324, No. 1, 1-8, 1991. [cited by applicant]
Wright et al., Activation of the Prolyl Hydroxylase Oxygen-Sensor Results in Induction of GLUTI, Heme Oxygenase-1, and Nitric-Oxide Synthase Proteins and Confers Protection from Metabolic Inhibition to Cardiomyocytes, J… [cited by applicant]
European Patent No. 2044005, Opposition Filed, Jul. 20, 2011. 51 pages. [cited by applicant]
European Patent No. 2044005, Response to Opposition, Dec. 28, 2011. 9 pages. [cited by applicant]
European Patent No. 2044005, Summons to Attend Oral Proceedings and Preliminary Opinion of the Opposition Division, Oct. 31, 2012. 5 pages. [cited by applicant]
European Patent No. 2044005, Decision of the Opposition Division, Instruction, and Grounds for the Decision, May 3, 2013. 21 pages. [cited by applicant]
European Patent No. 2044005, Patent Owner Statement of Grounds of Appeal, Sep. 13, 2013. 14 pages. [cited by applicant]
European Patent Office, Interlocutory Decision in Opposition Proceedings, mailed May 3, 2013, 76 pages. [cited by applicant]
European Patent Office, Minutes of the Oral Proceedings Before the Opposition Division, mailed May 3, 2013, 6 pages. [cited by applicant]
European Patent No. 2044005, Opponent Statement of Grounds of Appeal, Sep. 13, 2013. 16 pages. [cited by applicant]
European Patent No. 2044005, Opponent Reply to Appeal, Jan. 29, 2014. 30 pages. [cited by applicant]
European Patent No. 2044005, Patent Owner Reply to Appeal, Jan. 29, 2014. 26 pages. [cited by applicant]
European Patent No. 2044005, Patent Owner Response to the Opponent's Communication, Aug. 28, 2014. 50 pages. [cited by applicant]
European Patent No. 2044005, Communication of the Board of Appeal, Aug. 29, 2017. 12 pages. [cited by applicant]
European Patent No. 2044005, Response of Opponent to Communication of the Board of Appeal, Nov. 8, 2017. 30 pages. [cited by applicant]
Withdrawal of an Appeal by Proprietor in the Opposition Against European Patent No. 2044005, Feb. 27, 2018. 3 pages. [cited by applicant]
Decision of the Board of Appeal of the European Patent Office in the Opposition Against European Patent No. 2044005, Mar. 6, 2018. 6 pages. [cited by applicant]
Termination of Opposition Proceedings of European Patent No. 2044005, Apr. 18, 2018. 1 page. [cited by applicant]
Notice of Opposition u/s 25(2) filed on Sep. 25, 2018 by Dr. Reddy's Laboratories Limited against Indian Patent No. 287720. 237 pages. [cited by applicant]
Reply Statement of Patentee, filed Jan. 15, 2019, in the Post Grant Opposition against Indian Patent No. 287720 (39 pages). [cited by applicant]
Reply on Behalf of Opponent to the Counterstatement by the Patentee and Reply Evidence, submitted Feb. 14, 2019, in the Post Grant Opposition against Indian Patent No. 287720 (237 pages). [cited by applicant]