Granted Patent
B2
US 12,297,205 · App. 18/196,002 · Granted May 13, 2025
Macrocyclic compounds for treatment of medical disorders
Inventors:
Jason Allan Wiles (Madison, CT); Avinash S. Phadke (Branford, CT); Dawei Chen (Guilford, CT); Venkat Rao Gadhachanda (Hamden, CT); Joel Charles Barrish (Richboro, PA); Atul Agarwal (Hamden, CT); Kyle J. Eastman (New Haven, CT)
Assignee:
Achillion Pharmaceuticals, Inc.
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Abstract
Macrocyclic Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, and Formula VIII or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
Claims (16)
1. A compound selected from:
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
3. A method of inhibiting complement factor D, comprising administering to a patient in need thereof an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein the patient is human.
5. The method of claim 3 , wherein the patient has a complement factor D disorder selected from acute respiratory distress syndrome, age-related macular degeneration, arthritis, asthma, Alzheimer's dementia, amyotrophic lateral sclerosis, antibody-mediated transplant rejection, antineutrophil cytoplasm antibody-associated vasculitis, antiphospholipid syndrome, atypical or typical hemolytic uremic syndrome, cardiovascular disease, cold agglutinin disease, complement 3 glomerulopathy, chronic obstructive pulmonary disease, cirrhosis, Crohn's disease, C3 glomerulonephritis, diabetic retinopathy, dermatomyositis, dermatitis, epidermolysis bullosa acquisita, fatty liver, focal segmental glomerulosclerosis, geographic atrophy, glomerulonephritis, graft versus host disease, Guillain Barre syndrome, hemolytic anemia, hidradenitis suppurativa, IgA nephropathy, ischemia/reperfusion injury, liver failure, liver inflammation, lupus nephritis, membrane proliferative glomerulonephritis, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, neuromyelitis optica, nonalcoholic steatohepatitis, ocular disorder, ophthalmic disease, pancreatitis, paroxysmal nocturnal hemoglobinuria, pemphigoid, pemphigus vulgaris, pre-eclampsia, reduced glomerular filtration rate, renovascular disorder, respiratory disease, retinal detachment, rheumatoid arthritis, scleroderma, sepsis, Shiga toxin E. coli -related hemolytic uremic syndrome, spinal cord injury, sickle cell disease, traumatic brain injury, ulcerative colitis, and viral infection.
6. The method of claim 5 , wherein the disorder is a renovascular disorder.
7. The method of claim 5 , wherein the disorder is paroxysmal nocturnal hemoglobinuria.
8. The method of claim 5 , wherein the disorder is an ophthalmic disease.
9. The method of claim 5 , wherein the disorder is age-related macular degeneration or retinal detachment.
10. The method of claim 5 , wherein the disorder is geographic atrophy.
11. The method of claim 10 , wherein the disorder is sickle cell disease.
12. The method of claim 10 , wherein the disorder is myasthenia gravis.
13. The method of claim 5 , wherein the disorder is lupus nephritis.
14. The method of claim 5 , wherein the disorder is IgA nephropathy.
15. The method of claim 5 , wherein the disorder is a viral infection.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 16, 2023
From: WILES, JASON ALLAN; PHADKE, AVINASH S.; CHEN, DAWEI; GADHACHANDA, VENKAT RAO; BARRISH, JOEL CHARLES; AGARWAL, ATUL; EASTMAN, KYLE J.
To: ACHILLION PHARMACEUTICALS, INC.
Reel/Frame 064605/0100 →
Continuity (7)
Continuation
PCTUS2018020531
· Mar 1, 2018
Provisional Application
62500287
· May 2, 2017
Provisional Application
62466252
· Mar 2, 2017
Provisional Application
62465600
· Mar 1, 2017
References Cited (356)
US 6489476B1
· Dang et al.
· 2002
[cited by applicant]
US 6653340B1
· Babu et al.
· 2003
[cited by applicant]
US 7629340B2
· Schmitz et al.
· 2009
[cited by applicant]
US 8524716B2
· Raboisson et al.
· 2013
[cited by applicant]
US 9085555B2
· Altmann et al.
· 2015
[cited by applicant]
US 9421240B2
· Francois et al.
· 2016
[cited by applicant]
US 9468661B2
· Altmann et al.
· 2016
[cited by applicant]
US 9598446B2
· Gadhachanda et al.
· 2017
[cited by applicant]
US 9643986B2
· Wiles et al.
· 2017
[cited by applicant]
US 9663543B2
· Wiles et al.
· 2017
[cited by applicant]
US 9695205B2
· Wiles et al.
· 2017
[cited by applicant]
US 9732103B2
· Wiles et al.
· 2017
[cited by applicant]
US 9732104B2
· Gadhachanda et al.
· 2017
[cited by applicant]
US 9758537B2
· Wiles et al.
· 2017
[cited by applicant]
US 9796741B2
· Gadhachanda et al.
· 2017
[cited by applicant]
US 9828396B2
· Wiles et al.
· 2017
[cited by applicant]
US 20020133004A1
· Sekiyama et al.
· 2002
[cited by applicant]
US 20080075728A1
· Newman
· 2008
[cited by applicant]
US 20080108691A1
· Hamann et al.
· 2008
[cited by applicant]
US 20130344073A1
· Schwaeble et al.
· 2013
[cited by applicant]
US 20150079613A1
· Mcknight et al.
· 2015
[cited by applicant]
US 20150191462A1
· Hommel et al.
· 2015
[cited by applicant]
US 20150368271A1
· Su et al.
· 2015
[cited by applicant]
US 20160015810A1
· Deschatelets et al.
· 2016
[cited by applicant]
US 20160361329A1
· Wiles et al.
· 2016
[cited by applicant]
US 20160362399A1
· Wiles et al.
· 2016
[cited by applicant]
US 20160362432A1
· Wiles et al.
· 2016
[cited by applicant]
US 20160362433A1
· Wiles et al.
· 2016
[cited by applicant]
US 20170226142A1
· Wiles et al.
· 2017
[cited by applicant]
US 20180072762A1
· Wiles et al.
· 2018
[cited by applicant]
US 20180291046A1
· Wiles et al.
· 2018
[cited by applicant]
US 20180291047A1
· Wiles et al.
· 2018
[cited by applicant]
US 20190038623A1
· Huang et al.
· 2019
[cited by applicant]
CN 101506223A
· 2009
[cited by applicant]
CN 103402996A
· 2013
[cited by applicant]
CN 103561739A
· 2014
[cited by applicant]
CN 108024992A
· 2018
[cited by applicant]
CN 110603252A
· 2019
[cited by applicant]
EA 201890594A1
· 2018
[cited by applicant]
JP 2014506877A
· 2014
[cited by applicant]
JP 2015522005A
· 2015
[cited by applicant]
JP 2015522006A
· 2015
[cited by applicant]
JP 2015522007A
· 2015
[cited by applicant]
JP 2015522008A
· 2015
[cited by applicant]
JP 2015522062A
· 2015
[cited by applicant]
JP 2017511815A
· 2017
[cited by applicant]
JP 2018526367A
· 2018
[cited by applicant]
JP 6400738B2
· 2018
[cited by applicant]
JP 2018199714A
· 2018
[cited by applicant]
JP 6537532B2
· 2019
[cited by applicant]
JP 6688352B2
· 2020
[cited by applicant]
JP 7210637B2
· 2023
[cited by applicant]
KR 20140027090A
· 2014
[cited by applicant]
KR 1020160116014A
· 2016
[cited by applicant]
MX A2021003425
· 2021
[cited by applicant]
WO WO9320099A2
· 1993
[cited by applicant]
WO WO9529697A1
· 1995
[cited by applicant]
WO WO9948492A1
· 1999
[cited by applicant]
WO WO2004007501A1
· 2004
[cited by applicant]
WO WO2004045518A2
· 2004
[cited by applicant]
WO WO2004111041A1
· 2004
[cited by applicant]
WO WO2008047831A1
· 2008
[cited by applicant]
WO WO2009091826A2
· 2009
[cited by applicant]
WO WO2011057158A1
· 2011
[cited by applicant]
WO WO2012093101A1
· 2012
[cited by applicant]
WO WO2012177782A1
· 2012
[cited by applicant]
WO WO2013166436A1
· 2013
[cited by applicant]
WO WO2013192345A1
· 2013
[cited by applicant]
WO WO2014002051A2
· 2014
[cited by applicant]
WO WO2014002052A1
· 2014
[cited by applicant]
WO WO2014002053A1
· 2014
[cited by applicant]
WO WO2014002054A1
· 2014
[cited by applicant]
WO WO2014002057A1
· 2014
[cited by applicant]
WO WO2014002058A2
· 2014
[cited by applicant]
WO WO2014002059A1
· 2014
[cited by applicant]
WO WO2014005150A1
· 2014
[cited by applicant]
WO WO2014009833A2
· 2014
[cited by applicant]
WO WO2014037480A1
· 2014
[cited by applicant]
WO WO2014116880A1
· 2014
[cited by applicant]
WO WO2015008861A1
· 2015
[cited by applicant]
WO WO2015130784A1
· 2015
[cited by applicant]
WO WO2015130795A1
· 2015
[cited by applicant]
WO WO2015130806A1
· 2015
[cited by applicant]
WO WO2015130830A1
· 2015
[cited by applicant]
WO WO2015130838A1
· 2015
[cited by applicant]
WO WO2015130842A2
· 2015
[cited by applicant]
WO WO2015130845A1
· 2015
[cited by applicant]
WO WO2015130854A1
· 2015
[cited by applicant]
WO WO2017035348A1
· 2017
[cited by applicant]
WO WO2017035349A1
· 2017
[cited by applicant]
WO WO2017035351A1
· 2017
[cited by applicant]
WO WO2017035352A1
· 2017
[cited by applicant]
WO WO2017035353A1
· 2017
[cited by applicant]
WO WO2017035355A1
· 2017
[cited by applicant]
WO WO2017035357A1
· 2017
[cited by applicant]
WO WO2017035360A1
· 2017
[cited by applicant]
WO WO2017035361A1
· 2017
[cited by applicant]
WO WO2017035362A1
· 2017
[cited by applicant]
WO WO2017035401A1
· 2017
[cited by applicant]
WO WO2017035405A1
· 2017
[cited by applicant]
WO WO2017035408A1
· 2017
[cited by applicant]
WO WO2017035409A1
· 2017
[cited by applicant]
WO WO2017035411A1
· 2017
[cited by applicant]
WO WO2017035413A2
· 2017
[cited by applicant]
WO WO2017035415A1
· 2017
[cited by applicant]
WO WO2017035417A1
· 2017
[cited by applicant]
WO WO2017035418A1
· 2017
[cited by applicant]
WO WO2017098328A2
· 2017
[cited by applicant]
WO WO2017136395A1
· 2017
[cited by applicant]
WO WO2018005552A1
· 2018
[cited by applicant]
WO WO2018160889A1
· 2018
[cited by applicant]
WO WO2018160891A1
· 2018
[cited by applicant]
WO WO2018160892A1
· 2018
[cited by applicant]
WO WO2019028284A1
· 2019
[cited by applicant]
WO WO2019070714A1
· 2019
[cited by applicant]
WO WO2020041301A1
· 2020
[cited by applicant]
WO WO2020051538A1
· 2020
[cited by applicant]
WO WO2020069024A1
· 2020
[cited by applicant]
WO WO2020109343A1
· 2020
[cited by applicant]
WO WO2021021909A1
· 2021
[cited by applicant]
WO WO2021252669A1
· 2021
[cited by applicant]
WO WO2022047128A2
· 2022
[cited by applicant]
“Are There Any Treatments for ALS?” WebMD, <https://www.webmd.com/brain/understanding-als-treatment#1>, retrieved on May 3, 2019 (8 pages).
[cited by applicant]
“Arteriosclerosis/atherosclerosis,” Mayo Clinic, <https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/diagnosis-treatment/drc-20350575>, retrieved on Apr. 24, 2018 (10 pages).
[cited by applicant]
“Cancer,” MedLine Plus, <http://www.nlm.nih.gov/medlineplus/cancer.html>, retrieved Jul. 6, 2007 (10 pages).
[cited by applicant]
“Dermatomyositis,” Mayo Clinic, <https://www.mayoclinic.org/diseases-conditions/dermatomyositis/diagnosis-treatment/drc-20353192>, retrieved on Aug. 1, 2017 (7 pages).
[cited by applicant]
“History of Changes for Study: NCT03053102—A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH),” U.S. National Library of Medicine, available at: <https://clinicaltrials.gov/ct2/h…
[cited by applicant]
“NCT03472885—A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) With Inadequate Response to Eculizumab (PNH),” U.S. National Library of Medicine, available at: <https://clinicalt…
[cited by applicant]
“Reperfusion injury,” Wikipedia, <https://en.wikipedia.org/wiki/Reperfusion_injury>, retrieved Apr. 30, 2020 (8 pages).
[cited by applicant]
“Treatment for Multiple Sclerosis,” WebMD, <https://www.webmd.com/multiple-sclerosis/ms-treatment#1>, retrieved on May 3, 2019 (24 pages).
[cited by applicant]
“What Are the Treatments for Cirrhosis?,” WebMD, <https://www.webmd.com/digestive-disorders/understanding-cirrhosis-treatment#1>, retrieved May 3, 2019 (15 pages).
[cited by applicant]
“What is Cardiovascular Disease?” American Heart Association, <https://www.heart.org/en/health-topics/consumer-healthcare/what-is-cardiovascular-disease>, dated May 31, 2017 (4 pages).
[cited by applicant]
Airey et al., “A Convenient Preparation of Thieno[3,2-c]pyrazole,” Synthesis. 46: 96-100 (2014).
[cited by applicant]
Andrighetto et al., “Complement and Complement Targeting Therapies in Glomerular Diseases,” Int J Mol Sci. 20(24):6336 (Dec. 2019), available <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940904/>, retrieved on May 26,…
[cited by applicant]
Armand, “Fatty liver disease: What it is and what to do about it,” Harvard Health Publishing, <https://www.health.harvard.edu/blog/fatty-liver-disease-what-it-is-and-what-to-do-about-it-2019011015746>, dated Jan. 10, 20…
[cited by applicant]
Barraclough et al., “Synthesis of (2S,3R)- and (2S,3S)-[3-
[cited by applicant]
Barraclough et al., “Two separate and distinct syntheses of stereospecifically deuteriated samples of (2S)-proline,” Org Biomol Chem. 4(8):1483-1491 (2006).
[cited by applicant]
Carter, “Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease,” Scientifica. 2012(1):1-14 (2012) (14 pages).
[cited by applicant]
CAS RN 1236228-05-9, dated Aug. 16, 2010 (1 page).
[cited by applicant]
CAS RN 1236251-51-6, dated Aug. 17, 2010 (2 pages).
[cited by applicant]
CAS RN 1270608-88-2, dated 2019 (1 page).
[cited by applicant]
CAS RN 1277041-86-7, dated Apr. 8, 2011 (2 pages).
[cited by applicant]
Cole et al. “Structure of 3,4-Dichloroisocoumarin-Inhibited Factor D,” Acta Crystallogr D Biol Crystallogr. 54(Pt 5): 711-717 (1998).
[cited by applicant]
Compound Summary for CID 1129904, PubChem. <https://pubchem.ncbi.nlm.nih.gov/compound/1129904> retrieved Jul. 14, 2020, entered Jul. 10, 2005 (10 pages).
[cited by applicant]
Compound Summary for CID 118324207, PubChem, <https://pubchem.ncbi.nlm.nih.gov/compound/118324207>, created Feb. 23, 2016, retrieved on Jul. 14, 2020 (8 pages).
[cited by applicant]
Compound Summary for CID 123543544, PubChem, <https://pubchem.ncbi.nlm.nih.gov/compound/123543544>, created on Jan. 25, 2017, retrieved on Jul. 13, 2020 (8 pages).
[cited by applicant]
Compound Summary for CID 134222466, PubChem, <https://pubchem.ncbi.nlm.nih.gov/compound/134222466>, created on Jun. 23, 2018, retrieved on Jul. 14, 2020 (11 pages).
[cited by applicant]
Compound Summary for CID 59912842, PubChem, <https://pubchem.ncbi.nlm.nih.gov/compound/59912842>, entered Aug. 20, 2012, retrieved Jul. 14, 2020 (9 pages).
[cited by applicant]
Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN1236248-20-6, Entered STN: Aug. 16, 2010 (1 page).
[cited by applicant]
Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN1380849-41-1, Entered STN: Jul. 3, 2012 (2 pages).
[cited by applicant]
De Luca et al., “HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation,” Eur J Med Chem. 46(2): 756-764 (2011).
[cited by applicant]
DeZern et al., “Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia,” available in PMC Dec. 30, 2015, published in final edited form as: Hematol Oncol Clin North Am. 29(3):479-94 (Jun. 2015) (18 …
[cited by applicant]
Donthiri et al., “Copper-Catalyzed C—H Functionalization of Pyridines and Isoquinolines with Vinyl Azides: Synthesis of Imidazo Heterocycles,” J Org Chem. 79(22): 11277-11284 (2014).
[cited by applicant]
Dormoy et al., “Synthesis of N-t-Butoxycarbonyl-4,4-dideuterio-L-proline,” Synthesis. 1: 81-82 (1986).
[cited by applicant]
Ellis-Pegler et al., “An Orally Administered Small Molecule Factor D Inhibitor (ACH-4471) For Treatment of PNH and Complement Diseases: Preliminary Phase 1 Results In Healthy Volunteers,” European Hematology Association…
[cited by applicant]
Ellis-Pegler et al., “An Orally Administered Small Molecule Factor D Inhibitor (ACH-4471) For Treatment of PNH, C3G and Complement—Mediated Diseases: Interim Phase 1 Results In Healthy Volunteers,” European Hematology A…
[cited by applicant]
Extended European Search Report for European Application No. 19897806.6, dated Jul. 18, 2022 (12 pages).
[cited by applicant]
Gadhachanda et al., CAplus Database Summary Sheet for Document No. 164:507515, Accession No. 2016:627420, CAplus on STN. (Feb. 2018) (6 pages).
[cited by applicant]
Gavriilaki et al., “275 Small Molecule Factor D Inhibitors Block Complement Activation in Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome,” ASH 57th Annual Meeting & Exposition, Session: 101. …
[cited by applicant]
Gilkeson, “Complement-Targeted Therapies in Lupus,” Curr Treat Options in Rheum. 1:10-18 (Jan. 22, 2015).
[cited by applicant]
Golub et al., “Molecular classification of cancer: class discovery and class prediction by gene expression monitoring,” Science. 286(5439):531-7 (1999) (8 pages).
[cited by applicant]
Haddrill, “Stargardt's Disease (Fundus Flavimaculatus),” All About Vision, <https://www.allaboutvision.com/conditions/stargardts.htm#article-section-2>, retrieved May 3, 2019 (5 pages).
[cited by applicant]
Harris et al., “Developments in anti-complement therapy; from disease to clinical trial,” Mol Immunol. 102:89-119 (Oct. 2018).
[cited by applicant]
Hecker et al., “Liver-Targeted Prodrugs of 2'-C-Methyladenosine for Therapy of Hepatitis C Virus Infection,” J Med Chem. 50(16): 3891-3896 (2007).
[cited by applicant]
Hom et al., “Complement Inhibitors for Treatment of Geographic Atrophy and Advanced Nonexudative AMD,” Retinal Physician. 16:28-31 (Mar. 1, 2019) (7 pages).
[cited by applicant]
Hruby et al., “
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017523, dated May 14, 2015 (7 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017538, dated May 14, 2015 (8 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017554, dated May 14, 2015 (7 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017583, dated May 27, 2015 (12 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017593, dated Jun. 16, 2015 (6 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017597, dated Jan. 29, 2016 (10 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017600, dated May 27, 2015 (12 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/017609, dated May 29, 2015 (6 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048688, dated Dec. 28, 2016 (11 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048690, dated Dec. 28, 2016 (11 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048693, dated Jan. 13, 2017 (11 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048695, dated Dec. 30, 2016 (10 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048696, dated Jan. 5, 2017 (10 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048701, dated Jan. 10, 2017 (10 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048704, dated Dec. 27, 2016 (7 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048707, dated Jan. 5, 2017 (10 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048709, dated Jan. 17, 2017 (9 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048710, dated Jan. 5, 2017 (8 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048779, dated Dec. 27, 2016 (8 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048783, dated Feb. 3, 2017 (8 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048787, dated Jan. 5, 2017 (13 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048788, dated Jan. 5, 2017 (12 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048793, dated Dec. 28, 2016 (8 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048795, dated Feb. 17, 2017 (12 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048797, dated Jan. 5, 2017 (12 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048799, dated Nov. 15, 2016 (7 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/048800, dated Jan. 5, 2017 (12 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US18/20530, dated Jun. 25, 2018 (3 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US18/20531, dated May 15, 2018 (3 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2018/020528, dated Apr. 24, 2018 (3 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2019/034210, mailed Sep. 13, 2019 (4 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2019/047252, dated Dec. 17, 2019 (4 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2019/050065, dated Feb. 25, 2020 (4 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2019/053012, dated Jan. 28, 2020 (4 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US2019/066999, dated Feb. 12, 2020 (3 pages).
[cited by applicant]
Józsi, “Anti-Complement Autoantibodies in Membranoproliferative Glomerulonephritis and Dense Deposit Disease”,
[cited by applicant]
Kathuria, “Membranoproliferative Glomerulonephritis Medication,” Medscape, <https://emedicine.medscape.com/article/240056-medication>, dated Jun. 23, 2016, retrieved May 3, 2019 (1 page).
[cited by applicant]
Kinman, “COPD Drugs: A List of Medications to Help Relieve Your Symptoms,” Healthline, <https://www.healthline.com/health/copd/drugs>, retrieved on May 3, 2019 (12 pages).
[cited by applicant]
Kocinsky et al., “Abstract SaO018: Factor D inhibition with ACH-4471 to reduce complement alternative pathway hyperactivity and proteinuria in C3 glomerulopathy: preliminary proof of concept data,” Nephrology Dialysis T…
[cited by applicant]
Komiya et al., CAplus Database Summary Sheet for Document No. 162:229476, Accession No. 2015:126147, CAplus on STN. (Jul. 2017) (2 pages).
[cited by applicant]
Kuang et al., “Synthesis of (Z)-1-bromo-1-alkenes and terminal alkynes from anti-2,3-dibromoalkanoic acids by microwave-induced reaction,” Tetrahedron. 61(16):4043-4052 (2005).
[cited by applicant]
Lala et al., “Role of nitric oxide in tumor progression: lessons from experimental tumors,” Cancer Metastasis Rev. 17(1):91-106 (1998).
[cited by applicant]
Lassmann, “What drives disease in multiple sclerosis: Inflammation or neurodegeneration?” Clinical and Experimental Neuroimmunology. 1:2-11 (2010).
[cited by applicant]
MacKay et al., “Rapid Synthesis of the N-Methylwelwitindolinone Skeleton,” Org Lett. 7(16):3421-4 (2005).
[cited by applicant]
Mantegazza et al., “Complement Inhibition for the Treatment of Myasthenia Gravis,” Immunotargets Ther. 9:317-31 (Dec. 2020), <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751298/>, retrieved on May 26, 2022 (24 pages).
[cited by applicant]
Noris et al., “Overview of Complement Activation and Regulation,” Semin Nephrol. 33(6):479-92 (2013).
[cited by applicant]
Office Action issued for Eurasian Patent Application No. 201992005, dated Oct. 23, 2020 (6 pages).
[cited by applicant]
Okutani et al., “Conversion of Bromoalkenes into Alkynes by Wet Tetra-n-butylammonium Fluoride,” J Org Chem. 74(1):442-444 (2009).
[cited by applicant]
Oseini et al., “Therapies in Non-Alcoholic Steatohepatitis (NASH),” available in PMC Jan. 1, 2018, published in final edited form as: Liver Int. 37(Suppl 1):97-103 (Jan. 2017) (15 pages).
[cited by applicant]
Pandya et al., “Complement System in Lung Disease,” Am J Respir Cell Mol Biol. 51(4):467-473 (2014).
[cited by applicant]
Partial Supplementary European Search Report for European Application No. 18761960.6, dated Nov. 27, 2020 (12 pages).
[cited by applicant]
Patel et al., “In Vitro Combination Studies of ACH-4471 with Eculizumab to Assess a Potential ‘Switch’ Treatment Approach for Paroxysmal Nocturnal Hemoglobinuria,” 59th American Society of Hematology Annual Meeting and …
[cited by applicant]
Peifer et al., “Design, Synthesis, and Biological Evaluation of Novel 3-Aryl-4-(1H-indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as Vascular Endothelial Growth Factor Receptor (VEGF-R) Inhibitors,” J Med Chem. 51(13):3814-3…
[cited by applicant]
Pugsley et al., “Inhibitors of the complement system currently in development for cardiovascular disease,” Cardiovasc Toxicol. 3(1):43-69 (2003).
[cited by applicant]
Qu et al., “Recent Developments in Low Molecular Weight Complement Inhibitors,” available in PMC, Dec. 1, 2010, published in final edited form as: Mol Immunol. 47(2-3):185-195 (2009) (25 pages).
[cited by applicant]
Quesada et al., “One-pot conversion of activated alcohols into terminal alkynes using manganese dioxide in combination with the Bestmann—Ohira reagent,” Tetrahedron Letters. 46:6473-6476 (2005).
[cited by applicant]
Ricklin et al., “Complement in immune and inflammatory disorders: pathophysiological mechanisms,” J Immunol. 190(8):3831-3838 (2013) (9 pages).
[cited by applicant]
Rohrer et al., “Eliminating complement factor D reduces photoreceptor susceptibility to light-induced damage,” Invest Ophthalmol Vis Sci. 48(11):5282-9 (2007).
[cited by applicant]
Roth et al., “Further Improvements of the Synthesis of Alkynes from Aldehydes,” Synthesis. 1:59-62 (2004).
[cited by applicant]
Ruiz-Gómez et al., “Structure—Activity Relationships for Substrate-Based Inhibitors of Human Complement Factor B,” J Med Chem. 52(19):6042-6052 (2009).
[cited by applicant]
Salifu, “Chronic Glomerulonephritis Medication,” Medscape, <https://emedicine.medscape.com/article/239392-medication>, dated Feb. 1, 2017, retrieved on May 2, 2019 (1 page).
[cited by applicant]
Segers et al., “Complement Alternative Pathway Activation in Human Nonalcoholic Steatohepatitis,” PLOS ONE. 9(10):e110053 (2014) (9 pages).
[cited by applicant]
Stanton et al., “Complement Factor D in Age-Related Macular Degeneration,” Invest Ophthalmol Vis Sci. 52(12):8828-8834 (2011) (15 pages).
[cited by applicant]
Strobel et al., “Anti-factor B autoantibody in dense deposit disease,” Mol Immunol. 47:1476-1483 (2010).
[cited by applicant]
Tandon et al., “Substrate specificity of human prolyl-4-hydroxylase,” Bioorg Med Chem Lett. 8(10):1139-1144 (1998).
[cited by applicant]
Tang et al., “Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Bromides via tert-Butyl Isocyanide Insertion,” J Org Chem. 78(7):3170-3175 (2013).
[cited by applicant]
Varelas et al., “Complement in Sickle Cell Disease: Are We Ready for Prime Time?,” J Blood Med. 12:177-87 (2021), <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001680/>, dated Mar. 23, 2021, retrieved on May 26, 2022 (…
[cited by applicant]
Willows et al., “The role of complement in kidney disease,” Clin Med (Lond). 20(2):156-60 (Mar. 2020) (9 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US18/20528, mailed Apr. 24, 2018 (6 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US18/20530, mailed Jun. 25, 2018 (6 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US18/20531, mailed May 15, 2018 (7 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US19/47252, mailed Dec. 17, 2019 (6 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US19/50065, mailed Feb. 25, 2020 (7 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US19/53012, mailed Jan. 28, 2020 (5 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US19/66999, mailed Feb. 12, 2020 (7 pages).
[cited by applicant]
Yonemoto-Kobayashi et al., “Carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride in DMSO,” Org Biomol Chem. 11(23):3773-5 (2013).
[cited by applicant]
Yuan et al., “Small-molecule Factor D Inhibitors Selectively Block the Alternative Pathway of Complement in Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome,” Haematologica. 102(3):466-75 (Mar.…
[cited by applicant]
Caira, “Crystalline polymorphism of organic compounds,”
[cited by applicant]
Braga et al., “Crystal polymorphism and multiple crystal forms,” Structure Bond. 132:25-50 (2009).
[cited by applicant]
Extended European Search Report for European Application No. 21757829.3, dated May 27, 2024 (10 pages).
[cited by applicant]
Written Opinion for International Application No. PCT/US24/17823, mailed May 30, 2024 (6 pages).
[cited by applicant]
International Search Report for International Application No. PCT/US24/17823, mailed May 30, 2024 (3 pages).
[cited by applicant]
Ohlsson, Chapter 14: Urinary Biomarkers in Glomerulonephritis.
[cited by applicant]
Wiles et al., “Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471),” Curr Med Chem. 27(25):4165-80 (2020).
[cited by applicant]
Wermuth, Molecular Variations Based on Isosteric Replacements.
[cited by applicant]
“Complement Inhibitors as Therapeutic Agents,” Biopharma PEG, Jul. 11, 2022, available <https://www.biochempeg.com/article/281.html>, (11 pages).
[cited by applicant]
Garred et al., “Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics,” Pharmacol Rev. 73(2):792-827 (Apr. 2021).
[cited by applicant]
Iyer et al., “Chemical Approaches to Modulating Complement-Mediated Diseases,” J Med Chem. 61(8):3253-76 (Apr. 26, 2018).
[cited by applicant]