Granted Patent
B2
US 12,364,737 · App. 17/091,500 · Granted Jul 22, 2025
Activin receptor type IIA variants and methods of use thereof
Assignee:
Keros Therapeutics, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The invention features polypeptides that include an extracellular ActRIIA variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIA variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving low red blood cell levels, e.g., anemia or blood loss; fibrosis; or pulmonary hypertension.
Claims (12)
1. A method of treating anemia in a subject diagnosed as having anemia associated with a myelodysplastic syndrome or anemia associated with myelofibrosis, comprising: (i) measuring the subject's hemoglobin levels, followed by (ii) administering to the subject a therapeutically effective amount of a polypeptide comprising an extracellular ActRIIa variant, the variant having a sequence of GAILGRSETQECLX 1 X 2 NANWX 3 X 4 X 5 X 6 TNQTGVEX 7 CX 8 GX 9 X 10 X 11 X 12 X 13 X 14 HCX 15 ATWX 16 NISGSIEIVX 17 X 18 GCX 19 X 20 X 21 DX 22 NCYDRTDCVEX 23 X 24 X 25 X 26 PX 27 VYFCCCEGNMCNEKFSYFPEMEVTQPTS (SEQ ID NO: 1),
wherein X 1 is F or Y; X 2 is Y; X 3 is E; X 4 is L; X 5 is D or E; X 6 is R; X 7 is P or R; X 8 is E; X 9 is E; X 10 is K or Q; X 11 is D; X 12 is K; X 13 is R; X 14 is L; X 15 is F or Y; X 16 is K or R; X 17 is K; X 18 is K; X 19 is W; X 20 is L; X 21 is D; X 22 is I or F; X 23 is T; X 24 is K or E; X 25 is E; X 26 is N; and X 27 is Q.
2. The method of claim 1 , wherein the variant has the sequence of any one of SEQ ID NOs: 6-72.
3. The method of claim 1 , wherein the ActRIIa variant further comprises a C-terminal extension of one or more amino acids.
4. The method of claim 3 , wherein the C-terminal extension is NP or NPVTPK (SEQ ID NO: 155).
5. The method of claim 1 , wherein the polypeptide further comprises an Fc domain monomer, an Fc domain, an albumin-binding peptide, a fibronectin domain, or a human serum albumin fused to the C-terminus of the ActRIIa variant by way of a linker.
6. The method of claim 1 , wherein X 1 is F and X 10 is K.
7. The method of claim 2 , wherein the variant has the sequence of SEQ ID NO: 6, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 58, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, or SEQ ID NO: 72.
8. The method of claim 7 , wherein the variant has the sequence of SEQ ID NO: 69.
9. The method of claim 5 , wherein the polypeptide comprises an Fc domain monomer fused to the C-terminus of the ActRIIa variant by way of a linker.
10. The method of claim 9 , wherein the polypeptide is in the form of a homodimer.
11. The method of claim 1 , wherein the method further comprises monitoring the subject's hemoglobin levels in response to treatment.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 20, 2021
From: SEEHRA, JASBIR S.; LACHEY, JENNIFER
To: KEROS THERAPEUTICS, INC.
Reel/Frame 054971/0352 →
Continuity (4)
Continuation
PCTUS2019031573
· May 9, 2019
Provisional Application
62702735
· Jul 24, 2018
Provisional Application
62669075
· May 9, 2018
References Cited (382)
US 7612041B2
· Knopf et al.
· 2009
[cited by applicant]
US 7709605B2
· Knopf et al.
· 2010
[cited by applicant]
US 7842663B2
· Knopf et al.
· 2010
[cited by applicant]
US 7947646B2
· Sun et al.
· 2011
[cited by applicant]
US 7951771B2
· Knopf et al.
· 2011
[cited by applicant]
US 7960343B2
· Knopf et al.
· 2011
[cited by applicant]
US 7988973B2
· Sherman
· 2011
[cited by applicant]
US 8007809B2
· Sherman
· 2011
[cited by applicant]
US 8058229B2
· Seehra et al.
· 2011
[cited by applicant]
US 8067360B2
· Knopf et al.
· 2011
[cited by applicant]
US 8067562B2
· Han et al.
· 2011
[cited by applicant]
US 8101564B2
· Choi et al.
· 2012
[cited by applicant]
US 8138142B2
· Seehra et al.
· 2012
[cited by applicant]
US 8173601B2
· Knopf et al.
· 2012
[cited by applicant]
US 8178488B2
· Knopf et al.
· 2012
[cited by applicant]
US 8216997B2
· Seehra et al.
· 2012
[cited by applicant]
US 8252900B2
· Knopf et al.
· 2012
[cited by applicant]
US 8293881B2
· Seehra et al.
· 2012
[cited by applicant]
US 8343933B2
· Knopf et al.
· 2013
[cited by applicant]
US 8361957B2
· Seehra et al.
· 2013
[cited by applicant]
US 8367611B2
· Knopf et al.
· 2013
[cited by applicant]
US 8614292B2
· Han et al.
· 2013
[cited by applicant]
US 8629109B2
· Knopf et al.
· 2014
[cited by applicant]
US 8703927B2
· Seehra et al.
· 2014
[cited by applicant]
US 8710016B2
· Seehra et al.
· 2014
[cited by applicant]
US 8716459B2
· Sun et al.
· 2014
[cited by applicant]
US 8871209B2
· Stitt et al.
· 2014
[cited by applicant]
US 8895016B2
· Sherman
· 2014
[cited by examiner]
US 8999917B2
· Sun et al.
· 2015
[cited by applicant]
US 9138459B2
· Knopf et al.
· 2015
[cited by applicant]
US 9163075B2
· Knopf et al.
· 2015
[cited by applicant]
US 9181533B2
· Seehra et al.
· 2015
[cited by applicant]
US 9273114B2
· Sun et al.
· 2016
[cited by applicant]
US 9284364B2
· Han et al.
· 2016
[cited by applicant]
US 9353356B2
· Knopf et al.
· 2016
[cited by applicant]
US 9399669B2
· Knopf et al.
· 2016
[cited by applicant]
US 9439945B2
· Seehra et al.
· 2016
[cited by applicant]
US 9447165B2
· Sun et al.
· 2016
[cited by applicant]
US 9493556B2
· Seehra et al.
· 2016
[cited by applicant]
US 9505813B2
· Seehra et al.
· 2016
[cited by applicant]
US 9526759B2
· Knopf et al.
· 2016
[cited by applicant]
US 9572865B2
· Knopf et al.
· 2017
[cited by applicant]
US 9610327B2
· Sun et al.
· 2017
[cited by applicant]
US 9617319B2
· Seehra et al.
· 2017
[cited by applicant]
US 9745559B2
· Seehra et al.
· 2017
[cited by applicant]
US 9809638B2
· Sun et al.
· 2017
[cited by applicant]
US 9850298B2
· Attie
· 2017
[cited by applicant]
US 9932379B2
· Seehra et al.
· 2018
[cited by applicant]
US 20100028332A1
· Sherman
· 2010
[cited by examiner]
US 20100266591A1
· Bugelski et al.
· 2010
[cited by applicant]
US 20110250198A1
· Wolfman et al.
· 2011
[cited by applicant]
US 20120121576A1
· Seehra et al.
· 2012
[cited by applicant]
US 20130315924A1
· Hsu et al.
· 2013
[cited by applicant]
US 20160108379A1
· Knopf et al.
· 2016
[cited by applicant]
US 20160333418A1
· Haqq
· 2016
[cited by applicant]
US 20170327800A1
· Seehra et al.
· 2017
[cited by applicant]
US 20180125928A1
· Attie et al.
· 2018
[cited by applicant]
US 20180334673A1
· Wood et al.
· 2018
[cited by applicant]
US 20190330307A1
· Han et al.
· 2019
[cited by applicant]
US 20190352619A1
· Knopf et al.
· 2019
[cited by applicant]
US 20200071381A1
· Knopf et al.
· 2020
[cited by applicant]
US 20230265162A1
· Seehra et al.
· 2023
[cited by applicant]
US 20230348565A1
· Seehra et al.
· 2023
[cited by applicant]
AU 2013204964A1
· 2013
[cited by applicant]
AU 2016250354A1
· 2016
[cited by applicant]
EP 2303918
· 2009
[cited by applicant]
EP 2318028
· 2009
[cited by applicant]
EP 2314617A2
· 2011
[cited by applicant]
EP 2594280A1
· 2013
[cited by applicant]
JP 2008507288A
· 2008
[cited by applicant]
WO WO2004039948A2
· 2004
[cited by applicant]
WO WO2006012627A3
· 2006
[cited by applicant]
WO WO2006012627A2
· 2006
[cited by examiner]
WO WO2008076437A2
· 2008
[cited by applicant]
WO WO2008094708A2
· 2008
[cited by applicant]
WO WO2008097541A2
· 2008
[cited by applicant]
WO WO2008100384A2
· 2008
[cited by applicant]
WO WO2009015345A1
· 2009
[cited by applicant]
WO WO2009158015A2
· 2009
[cited by applicant]
WO WO2009158015A3
· 2009
[cited by applicant]
WO WO2009158025A2
· 2009
[cited by applicant]
WO WO2009158033A2
· 2009
[cited by examiner]
WO WO2009158035A2
· 2009
[cited by examiner]
WO WO2010062383A2
· 2010
[cited by applicant]
WO WO2010083034A1
· 2010
[cited by applicant]
WO WO2010151426A1
· 2010
[cited by applicant]
WO WO2011020045A1
· 2011
[cited by applicant]
WO WO2011031901A1
· 2011
[cited by applicant]
WO WO2011056896A1
· 2011
[cited by applicant]
WO WO2011063018A1
· 2011
[cited by applicant]
WO WO2012027065A2
· 2012
[cited by examiner]
WO WO2012064771A1
· 2012
[cited by applicant]
WO WO2013059347A1
· 2013
[cited by applicant]
WO WO2013188448A3
· 2013
[cited by applicant]
WO WO2014066487A2
· 2014
[cited by applicant]
WO WO2014138485A1
· 2014
[cited by applicant]
WO WO2014144903A1
· 2014
[cited by applicant]
WO WO2015143403A1
· 2015
[cited by applicant]
WO WO2015161220A1
· 2015
[cited by applicant]
WO WO2015192111A1
· 2015
[cited by applicant]
WO WO2015192127A2
· 2015
[cited by applicant]
WO WO2016069234A1
· 2016
[cited by applicant]
WO WO2016090188A1
· 2016
[cited by applicant]
WO WO2016164501A1
· 2016
[cited by applicant]
WO WO2016171948A1
· 2016
[cited by applicant]
WO WO2016187378A1
· 2016
[cited by examiner]
WO WO2017079591A2
· 2017
[cited by applicant]
WO WO2017091706A1
· 2017
[cited by applicant]
WO WO2017147182A1
· 2017
[cited by applicant]
WO WO2018013936A1
· 2018
[cited by applicant]
WO WO2018022762A1
· 2018
[cited by applicant]
WO WO2018067740A1
· 2018
[cited by applicant]
WO WO2018067874A1
· 2018
[cited by applicant]
WO WO2018075747A1
· 2018
[cited by applicant]
WO WO2018089706A2
· 2018
[cited by applicant]
WO WO2018089715A1
· 2018
[cited by applicant]
WO WO2018100483A1
· 2018
[cited by applicant]
WO WO2018144542A1
· 2018
[cited by applicant]
WO WO2018144968A1
· 2018
[cited by applicant]
WO WO2018231905A1
· 2018
[cited by applicant]
WO WO2019094751A1
· 2019
[cited by applicant]
WO WO2019140283A1
· 2019
[cited by applicant]
WO WO2021062163A1
· 2021
[cited by applicant]
WO WO2021189006A1
· 2021
[cited by applicant]
WO WO2021189010A1
· 2021
[cited by applicant]
WO WO2021189019A1
· 2021
[cited by applicant]
WO WO2022072882A1
· 2022
[cited by applicant]
WO WO2022235620A1
· 2022
[cited by applicant]
WO WO2022271716A2
· 2022
[cited by applicant]
WO WO2023023345A2
· 2023
[cited by applicant]
WO WO2024054985A2
· 2024
[cited by applicant]
WO WO2024102906A2
· 2024
[cited by applicant]
Carrancio et al., An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin. Br J Haematol. Jun. 2014;165(6):870-82. doi: 10.1111/bjh.12838. Epub Mar. …
[cited by examiner]
Dussiot et al., An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia. Nat Med. Apr. 2014;20(4):398-407. doi: 10.1038/nm.3468. Epub Mar. 23, 2014. PMID: 24658077; PMCID: PMC7730561 (Ye…
[cited by examiner]
Langdon et al., RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice. Am J Hematol. Jan. 2015;90(1):8-14. doi: 10.1002/ajh.23856. Epub Oct. 25, 2014. PMID: 25236856; P…
[cited by examiner]
Mulivor et al., RAP-011, a Soluble Activin Receptor Type lla Murine IgG-Fc Fusion Protein, Prevents Chemotherapy Induced Anemia., Blood, vol. 114, Issue 22, 2009, p. 161, ISSN 0006-4971, https://doi.org/10.1182/blood.V1…
[cited by examiner]
El-Halabi et al., Under-diagnosing and under-treating iron deficiency in hospitalized patients with gastrointestinal bleeding. World J Gastrointest Pharmacol Ther. Feb. 6, 2016;7(1):139-44. doi: 10.4292/wjgpt.v7.i1.139.…
[cited by examiner]
Guralnik et al., Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. Oct. 15, 2004;104(8):2263-8. doi: 10.1182/blood-2004-05-1812. Epub Jul. 6,…
[cited by examiner]
Efstratiadis et al.,Cardio-renal anemia syndrome. Hippokratia. Jan. 2008; 12(1):11-6. PMID: 18923761; PMCID: PMC2532969 (Year: 2008).
[cited by examiner]
Cascio et al., Anemia: Evaluation and Diagnostic Tests. Med Clin North Am. Mar. 2017;101(2):263-284. doi: 10.1016/j.mcna.2016.09.003. Epub Dec. 8, 2016. PMID: 28189170 (Year: 2016).
[cited by examiner]
Germing et al., Myelodysplastic syndromes: diagnosis, prognosis, and treatment. Dtsch Arztebl Int. Nov. 15, 2013;110(46):783-90. doi: 10.3238/arztebl.2013.0783. PMID: 24300826; PMCID: PMC3855821 (Year: 2013).
[cited by examiner]
Savona, Are we altering the natural history of primary myelofibrosis?, Leuk Res. Sep. 2014;38(9):1004-12. doi: 10.1016/j.leukres.2014.04.012. Epub May 9, 2014. PMID: 24931396 (Year: 2014).
[cited by examiner]
Weidner et al., Myelodysplastic syndromes and bone loss in mice and men. Leukemia 31, 1003-1007 (2017). https://doi.org/10.1038/leu.2017.7 (Year: 017).
[cited by examiner]
Eisenstaedt et al., Anemia in the elderly: current understanding and emerging concepts. Blood Rev. Jul. 2006;20(4):213-26. doi: 10.1016/j.blre.2005.12.002. Epub Feb. 10, 2006. PMID: 16472893 (Year: 2006).
[cited by examiner]
Naymagon et al., Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies. Hemasphere. Dec. 20, 2017;1(1):e1. doi: 10.1097/HS9.0000000000000001. PMID: 31723730; PMCID: PMC6745971 (Year: 2017).
[cited by examiner]
Aversa et al., Cancer-induced muscle wasting: latest findings in prevention and treatment. Ther Adv Med Oncol. May 2017;9(5):369-382. doi: 10.1177/1758834017698643. Epub Mar. 8, 2017. PMID: 28529552; PMCID: PMC5424865 (…
[cited by examiner]
Mellibovsky et al., Relationship among densitometry, bone histomorphometry, and histologic stage in idiopathic myelofibrosis. Bone. Feb. 2004;34(2):330-5. doi: 10.1016/j.bone.2003.10.010. PMID: 14962811 (Year: 2004).
[cited by examiner]
“Keros Therapeutics Presents Results from Preclinical Studies Investigating KER-012 at the American Society for Bone and Mineral Research 2020 Annual Meeting,” Keros Therapeutics, <https://www.globenewswire.com/news-rel…
[cited by applicant]
Marisavljevic et al., “Myelofibrosis in primary myelodysplastic syndromes: clinical and biological significance,” Med Oncol. 21(4):325-31 (2004) (Abstract only) (2 pages).
[cited by applicant]
Morgenroth et al., “Insights into bone health in Duchenne muscular dystrophy,” Bonekey Rep. 1:9 (2012) (11 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/023353, mailed Jul. 20, 2021 (9 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/023339, mailed Jun. 21, 2021 (23 pages).
[cited by applicant]
Kuo et al., “MB109 as bioactive human bone morphogenetic protein-9 refolded and purified from
[cited by applicant]
Wu et al., “Identification and analysis of type II TGF-beta receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells,” Acta Biochim Biophys Sin (Shanghai). 42(10):699-708 (2010).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/023335, mailed Jul. 9, 2021 (29 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/053239, mailed Feb. 23, 2022 (13 pages).
[cited by applicant]
Rodgarkia-Dara et al., “The activin axis in liver biology and disease,” Mutat Res. 613(2-3):123-37 (2006).
[cited by applicant]
Ballen et al., “Outcome of transplantation for myelofibrosis,” Biol Blood Marrow Transplant. 16(3):358-67 (Mar. 2010).
[cited by applicant]
Stegelmann et al., “Updated Results from the German Mpnsg-0212 Combination Trial: Ruxolitinib Plus Pomalidomide in Myelofibrosis with Anemia,” Blood. 134(Supplement_1):672 (5 pages) (Nov. 2019).
[cited by applicant]
Bose et al. “Management of Myelofibrosis-Related Cytopenias,” Curr Hematol Malig Rep. 13(3):164-172 (May 2018).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/040920, dated Mar. 29, 2023 (13 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/034366, mailed Jan. 4, 2023 (13 pages).
[cited by applicant]
Humeniuk et al., “Brief Report: Loss of p15Ink4b Accelerates Development of Myeloid Neoplasms in Nup98-HoxD13 Transgenic Mice,” Stem Cells. 32(5):1361-1366 (2014).
[cited by applicant]
Park et al., “The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion.” Ann Hematol. 99(1):7-19 (Jan. 2020).
[cited by applicant]
Feigenson et al., “Ker-050, a Modified Actriia Ligand Trap, Alleviates Cytopenia Arising from Multiple Etiologies,” Blood. 136(Supplement_1):38 (2 Pages) (Nov. 2020).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/027399, mailed Sep. 21, 2022 (14 pages).
[cited by applicant]
Fenaux et al., “Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis,” Blood. 133(8):790-794 (Feb. 2019) (5 pages).
[cited by applicant]
Tournier et al., “Calibrated automated thrombography demonstrates hypercoagulability in patients with idiopathic pulmonary arterial hypertension,” Thrombosis Res. 126:e418-e422 (2010) (5 pages).
[cited by applicant]
Rabinovitch et al., “Inflammation and Immunity in the Pathogenesis of Pulmonary Arterial Hypertension,” Circ Res. 115(1):165-175 (Jun. 2014) (11 pages).
[cited by applicant]
Highland et al., “Development of the Pulmonary Hypertension Functional Classification Self-Report: a patient version adapted from the World Health Organization Functional Classification measure,” Health Qual Life Outcom…
[cited by applicant]
Hoffmann et al., “Compartment-specific expression of collagens and their processing enzymes in intrapulmonary arteries of IPAH patients,” Am J Physiol Lung Cell Mol Physiol. 308(10):L1002-L1013 (2015) (12 pages).
[cited by applicant]
Bauer et al., “Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice,” PLoS ONE 6(12):e28578 (Dec. 2011) (10 pages).
[cited by applicant]
Ogawa et al., “Long-term patient survival with idiopathic/heritable pulmonary arterial hypertension treated at a single center in Japan,” Life Science 118(2):414-419 (2014) (6 pages).
[cited by applicant]
Galiè et al., “2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC…
[cited by applicant]
Huertas et al., “Immune Dysregulation and Endothelial Dysfunction in Pulmonary Arterial Hypertension: a complex interplay,” Circulation. 129(12):1332-40 (Mar. 2014) (9 pages).
[cited by applicant]
Yndestad et al., “Elevated levels of activin A in clinical and experimental pulmonary hypertension,” J Appl Physiol 106(4):1356-1364 (2009) (9 pages).
[cited by applicant]
“A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01999582?ter…
[cited by applicant]
“A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT02230917?term=sotatercept&draw=2&rank=4>, first posted S…
[cited by applicant]
“A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH) (PULSAR),” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT03496207?term=sotatercept&draw=2&rank=3>, first posted Apr…
[cited by applicant]
“A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (SPECTRA),” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT03738150?term=sotatercept&draw=2&rank=1>, first posted Nov. 13,…
[cited by applicant]
“Efficacy and Safety Study of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects Who Require Red…
[cited by applicant]
“Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia (ACE-011-DBA),” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01464164?term=sotatercept&draw=2&…
[cited by applicant]
“Sotatercept in Treating Patients With Myeloproliferative Neoplasm-Associated Myelofibrosis or Anemia,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01712308?term=sotatercept&draw=2&rank=8>, first …
[cited by applicant]
“Study of ACE-536 for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS),” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01749514?term=luspatercept&draw=2&rank=12>, first poste…
[cited by applicant]
“Study of ACE-536 in Healthy Postmenopausal Women,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01432717?term=luspatercept&draw=2&rank=13>, first posted Sep. 13, 2011, retrieved Mar. 30, 2020 (5 p…
[cited by applicant]
“Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML),” U.S. National Library of Medicine, <clinicalt…
[cited by applicant]
“Study to Evaluate Effect of a Single Dose of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Subjects With Solid Tumors,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01190644?te…
[cited by applicant]
“Study to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NCT01749540?term=luspatercept&draw=2&rank=11>, first posted Dec. 13, 2012, re…
[cited by applicant]
“To Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer,” U.S. National Library of Medicine, <clinicaltrials.gov/ct2/show/NC…
[cited by applicant]
“To Document the Burden of Illness on the Quality of Life and the Impact on Healthcare Utilization in (Beta)-thalassemia Subjects Who Are Transfusion Dependent (TD) and Non-transfusion Dependent (NTD) Receiving Standard…
[cited by applicant]
Abdulkadyrov et al., “Sotatercept in Patients with Osteolytic Lesions of Multiple Myeloma,” Br J Haematol. 165(6):814-823 (2014).
[cited by applicant]
Akpan et al., “The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity,” available in PMC May 1, 2010, published in final edited form as: Int J Obes (Lond). 33(11):1265-73 (2009) (17 pages).
[cited by applicant]
Attie et al., “A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers,” Am J Hematol. 89(7): 766-770 (2014) (5 pages).
[cited by applicant]
Attie et al., “A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers.” Muscle Nerve. 47(3):416-23 (2013).
[cited by applicant]
Badesch et al., “PULSAR: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Sotatercept (ACE-011) When Added to Standard of Care for the Treatment of Pulmonary Arterial Hy…
[cited by applicant]
Bernstein et al., “Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP…
[cited by applicant]
Bond et al., “Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets,” Int J Biol Sci. 12(5):617-30 (2016).
[cited by applicant]
Cadena et al., “Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type,” J Appl Physiol. 109(3):635-642 (2010).
[cited by applicant]
Cappellini et al., “A Phase 2a, Open-Label, Dose-Finding Study To Determine The Safety and Tolerability Of Sotatercept (ACE-011) In Adults With Beta-Thalassemia: Interim Results,” 55th Annual Meeting of the American Soc…
[cited by applicant]
Carlson et al., “Soluble Activin Receptor Type IIB Increases Forward Pulling Tension in the MDX Mouse,” available in PMC May 1, 2012, published in final edited form as: Muscle Nerve. 43(5):694-699 (2011) (11 pages).
[cited by applicant]
Carrancio et al., “An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin,” Br J Haematol. 165(6):870-882 (2014).
[cited by applicant]
Cash et al., “The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding,” EMBO J. 28(17):2662-76 (2009).
[cited by applicant]
Chantry et al., “Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo.” J Bone Miner Res. 25(12):2633-46 (2010).
[cited by applicant]
Chen et al., “Pharmacokinetics and Exposure-Response of Luspatercept in Patients With Anemia Due to Low- or Intermediate-1-Risk Myelodysplastic Syndromes (MDS): Preliminary Results From Phase 2 Studies,” 58th Annual Mee…
[cited by applicant]
Chen et al., “Pharmacokinetics and Exposure-Response of Luspatercept in Patients With Beta-Thalassemia: Preliminary Results From Phase 2 Studies,” 58th Annual Meeting of the American Society of Hematology (ASH), Dec. 3-…
[cited by applicant]
Dellanna, “Safety and Hemoglobin Effect of Sotatercept, Administered Intravenously and Subcutaneously, for Maintenance of Hemoglobin in Hemodialysis Subjects: Interim Analysis of a Phase 2 Study,” 48th Annual American S…
[cited by applicant]
DiGirolamo et al., “Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta,” Bone Res. 3:14042 (2015) (6 pages).
[cited by applicant]
Dussiot et al., “An activin receptor IIA ligand trap corrects ineffective erythropoiesis in beta-thalassemia,” Nat Med. 20(4):398-407 (2014) (12 pages).
[cited by applicant]
El-Shahawy et al., “Interim Analysis of ACE-011-REN-001: The First 28 Day Dose Cycle of Low and Medium Starting Doses of Sotatercept Compared to Placebo for Correction of Anemia in Hemodialysis Subjects,” National Kidne…
[cited by applicant]
El-Shahawy et al., “Long-term Effects of Sotatercept Compared With Placebo for Correction of Anemia in Hemodialysis Subjects: Interim Analysis of ACE-011-REN-001 Phase 2A Study,” 51st Congress of the European Renal Asso…
[cited by applicant]
El-Shahawy et al., “Safety and Hemoglobin Effect of the First 28-Day Dose Cycle of Sotatercept 0.7 mg/kg Compared With Lower Doses and Placebo for Correction of Anemia in Hemodialysis Subjects: Interim Analysis,” Americ…
[cited by applicant]
Fajardo et al., “Treatment with a soluble receptor for activin improves bone mass and structure in the axial and appendicular skeleton of female cynomolgus macaques (Macaca fascicularis),” Bone. 46(1):64-71 (2010).
[cited by applicant]
Fakhfakh et al., “Administration of a soluble activin type IIB receptor promotes the transplantation of human myoblasts in dystrophic mice,” available in PMC Jul. 10, 2014, published in final edited form as: Cell Transp…
[cited by applicant]
Fenaux et al., “Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in IPSS-R Very Low-, Low-, or Int-Risk RBC Transf…
[cited by applicant]
Fenaux et al., “The MEDALIST Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) A…
[cited by applicant]
Fields et al., “Activin receptor antagonists for cancer-related anemia and bone disease,” Exp Opin Invest Drugs. 22(1):87-101 (2013).
[cited by applicant]
Garcia-Manero et al., “Hematologic Improvement-Neutrophil and -Platelet in the MEDALIST Trial: Multilineage Data from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Pati…
[cited by applicant]
Gerds et al., “A Phase 2 Study of Luspatercept in Patients With Myelofibrosis-Associated Anemia,” 61st Annual Meeting of the American Society of Hematology (ASH), Dec. 7-10, Orlando FL, Presentation, Abstract 557, retri…
[cited by applicant]
Giagounidis et al., “Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients With Lower-Risk Myelodysplastic Syndromes (MDS): Long-Term Results From the Phase 2 PACE-MDS Study,” 22nd European Hemato…
[cited by applicant]
Giagounidis et al., “Luspatercept Treatment Leads to Long Term Increases in Hemoglobin and Reductions in Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Result…
[cited by applicant]
Graham et al., “A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury,” J Neurotrauma. 33(12):1128-1135 (2016).
[cited by applicant]
Guo et al., “Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity,” PLoS One. 4(3):e4937 (2009) (11 pages).
[cited by applicant]
Guo et al., “Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy,” Diabetes. 61(10):2414-23 (2012).
[cited by applicant]
Havill et al., “Sotatercept Improves Anemia, Vascular Calcification, and Bone Loss in Patients With End-Stage Kidney Disease on Hemodialysis,” American Society of Nephrology Kidney Week 2015, Nov. 5-8, San Diego, CA, Po…
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US17/60960, mailed Aug. 9, 2018 (14 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US17/60970, mailed Mar. 27, 2018 (15 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2018/060076, mailed Mar. 14, 2019 (18 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/013329, mailed May 13, 2019 (19 pages).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/031573, mailed Sep. 17, 2019 (16 pages).
[cited by applicant]
Joshi et al., “ActRIIA-Fc (Sotatercept) Reverses Pulmonary Vascular Remodeling to Attenuate Pulmonary Arterial Hypertension by Rebalancing Activin/BMP Signaling in a Preclinical Model,” American Thoracic Society 2019 In…
[cited by applicant]
Joshi et al., “RAP-011, a Murine Ortholog of ACTRIIA-FC (Sotatercept), Improves Pulmonary Hemodynamics and Restores Right Ventricular Structure and Function in a Preclinical Model of Severe Angio-obliterative Pulmonary …
[cited by applicant]
Komrokji et al., “A Phase 2, Dose-Finding Study of Sotatercept (ACE-011) in Patients with Lower-Risk Myelodysplastic Syndromes or Non-Proliferative Chronic Myelomonocytic Leukemia and Anemia Requiring Transfusion,” The …
[cited by applicant]
Komrokji et al., “An Open-Label, Phase 2, Dose-Finding Study of Sotatercept (ACE-011) in Patients with Low or Intermediate (Int)-1-Risk Myelodysplastic Syndromes (MDS) or Non-Proliferative Chronic Myelomonocytic Leukemi…
[cited by applicant]
Lee et al., “Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development,” available in PMC Nov. 1, 2011, published in final edited form as: Dev Biol. 347(1):195-203 (2010)…
[cited by applicant]
Lee et al., “Myostatin and the control of skeletal muscle mass,” Curr Opin Genet Devel. 9(5):604-607 (1999).
[cited by applicant]
Lee et al., “Regulation of muscle growth by multiple ligands signaling through activin type II receptors,” Proc Natl Acad Sci U S A. 102(50):18117-18122 (2005).
[cited by applicant]
Lee et al., “Regulation of myostatin activity and muscle growth,” Proc Natl Acad Sci U S A. 98(16):9306-9311 (2001).
[cited by applicant]
Lee et al., “Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway,” Proc Natl Acad Sci U S A. 109(35):E2353-60 (2012).
[cited by applicant]
Lotinun et al., “A soluble activin receptor Type IIA fusion protein (ACE-011) increases bone mass via a dual anabolic-antiresorptive effect in Cynomolgus monkeys.” Bone. 46(4):1082-8 (2010).
[cited by applicant]
MacDonald et al., “Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition,” first posted online on Feb. 6, 2014, published in final edited form as: Dis Model Mech. 7(4…
[cited by applicant]
Malluche et al., “Sotatercept: Initial Signal-Seeking Quantitative Computed Tomography Results for Bone Mass and Vascular Calcification in Hemodialysis Subjects Treated With Escalating Doses: Interim Analysis of ACE-011…
[cited by applicant]
Malluche et al., “The Role of Activin Signaling in the Pathogenesis of Renal Osteodystrophy of CKD-MBD,” 52nd ERA-EDTA Congress, May 28-31, London, United Kingdom, Poster FP406, retrieved from <acceleronpharma.com/wp-co…
[cited by applicant]
Martinez, “Luspatercept Inhibits pSmad2/3 Signaling and Promotes Erythroid Maturation Through a GATA1 Dependent Mechanism,” 23rd European Hematology Association Congress, Jun. 14-17, Stockholm, Sweden, Oral Presentation…
[cited by applicant]
Martinez, “RAP-536 (Murine ACE-536/Luspatercept) Inhibits Smad2/3 Signaling and Promotes Erythroid Differentiation By Restoring GATA1 Function in Murine Beta-thalassemia,” 21st European Hematology Association Congress, …
[cited by applicant]
Martinez, “RAP-536 (Murine ACE-536/Luspatercept) Inhibits Smad2/3 Signaling and Promotes Erythroid Differentiation By Restoring GATA1 Function in Murine Beta-thalassemia,” Oral Presentation, Blood. 126(23):751 (2015) (2…
[cited by applicant]
McPherron et al., “Double muscling in cattle due to mutations in the myostatin gene,” Proc Natl Acad Sci USA. 94(23):12457-61 (1997).
[cited by applicant]
McPherron et al., “GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines*,” J Biol Chem. 268(5):3444-3449 (1993) (7 pages).
[cited by applicant]
McPherron et al., “Redundancy of myostatin and growth/differentiation factor 11 function,” BMC Dev Biol. 9:24 (2009) (9 pages).
[cited by applicant]
McPherron et al., “Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11,” Nat Genet. 22(3):260-264 (1999).
[cited by applicant]
McPherron et al., “Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member,” Nature. 387(6628):83-90 (1997).
[cited by applicant]
McPherron et al., “Soluble activin receptor type IIB treatment does not cause fat loss in mice with diet-induced obesity,” available in PMC Mar. 1, 2013, published in final edited form as: Diabetes Obes Metab. 14(3):279…
[cited by applicant]
McPherron et al., “Suppression of body fat accumulation in myostatin-deficient mice,” J Clin Invest. 109(5):595-601 (2002).
[cited by applicant]
McPherron et al., “The transforming growth factor beta superfamily,” Growth Factors and Cytokines in Health and Disease. 1:357-393 (1996).
[cited by applicant]
Mesa et al., “A Phase 2, Multicenter, Open-Label Study of the Safety and Efficacy of Luspatercept in Subjects With Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis and Anemia With or Without RBC Transfusion De…
[cited by applicant]
Morine et al., “Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of Duchenne muscular dystrophy,” available in PMC Jul. 17, 2015, published in final edited form as: Muscle Nerve. 42(5):722-…
[cited by applicant]
Ngo et al.
[cited by applicant]
Nielsen et al., “Postnatal Hyperplasic Effects of ActRIIB Blockade in a Severely Dystrophic Muscle,” J Cell Physiol. 232(7):1774-1793 (2016) (21 pages).
[cited by applicant]
Paulson, “Targeting a new regulator of erythropoiesis to alleviate anemia,” Nat Med. 20(4):334-335 (2014).
[cited by applicant]
Pearsall et al., “A soluble activin type IIA receptor induces bone formation and improves skeletal integrity,” Proc Nat Acad Sci U S A. 105(19):7082-7087 (2008).
[cited by applicant]
Piga et al., “Improvements in Hemoglobin, Quality of Life, and Six-Minute-Walk Distance in Adults with beta-Thalassemia Treated with Luspatercept: Long-Term Phase 2 Study,” 23rd European Hematology Association Congress,…
[cited by applicant]
Piga et al., “Luspatercept (ACE-536) Increases Hemoglobin and Decreases Transfusion Burden and Liver Iron Concentration in Adults with Beta-Thalassemia: Preliminary Results from a Phase 2 Study,” EHA (2015) (22 pages).
[cited by applicant]
Piga et al., “Luspatercept (ACE-536) Increases Hemoglobin and Decreases Transfusion Burden and Serum Ferritin in Adults with Beta-Thalassemia: Preliminary Results from a Phase 2 Study,” American Society of Hematology, O…
[cited by applicant]
Piga et al., “Luspatercept Decreases Transfusion Burden and Liver Iron Concentration in Regularly Transfused Adults with Beta-Thalassemia,” 21st European Hematology Association Congress, Jun. 9-12, Copenhagen, Denmark, …
[cited by applicant]
Piga et al., “Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS): Long-Term Results From Phase 2 PACE-MDS Study,” 21st European Hemato…
[cited by applicant]
Piga et al., “Luspatercept Increases Hemoglobin, Decreases Transfusion Burden, and Improves Patient-Reported Outcomes in Adults with Beta-Thalassemia,” 58th Annual Meeting of the American Society of Hematology (ASH), De…
[cited by applicant]
Piga et al., “Luspatercept Increases Hemoglobin, Reduces Liver Iron Concentration and Improves Quality of Life in Non-Transfusion Dependent Adults with Beta-Thalassemia,” 21st European Hematology Association Congress, J…
[cited by applicant]
Piga et al., “Luspatercept Increases Hemoglobin, Reduces Liver Iron Concentration and Improves Quality of Life in Non-Transfusion Dependent Adults with Beta-Thalassemia,” 2nd MEGMA Conference, Nov. 11-12, Amman, Jordan,…
[cited by applicant]
Platzbecker et al., “Biomarkers of Ineffective Erythropoiesis Predict Response to Luspatercept in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Final Results from the Phase 2 PACE-MDS Study,”…
[cited by applicant]
Platzbecker et al., “Luspatercept (ACE-536) Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results from a Phase 2 Study,” Ame…
[cited by applicant]
Platzbecker et al., “Luspatercept Increases Hemoglobin And Reduces Transfusion Burden In Patients With Low Or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results From A Phase 2 Study,” EHA MDS Oral …
[cited by applicant]
Platzbecker et al., “Luspatercept Increases Hemoglobin And Reduces Transfusion Burden In Patients With Low Or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results From A Phase 2 Study,” Advancing Res…
[cited by applicant]
Platzbecker et al., “Luspatercept Response in New Subpopulations of Patients With Lower-Risk Myelodysplastic Syndromes (MDS): Update of the PACE Study,” 14th International Symposium on Myelodysplastic Syndromes, May 3-6…
[cited by applicant]
Platzbecker et al., “Luspatercept Significantly Reduces Red Blood Cell (RBC) Transfusion Burden, Regardless of Gene Mutation Frequency, Spectrum, and Prognostic Significance, Among Patients with Lower-Risk Myelodysplast…
[cited by applicant]
Platzbecker et al., “Mutational and Subgroup Analyses of Lower-Risk Myelodysplastic Syndromes (MDS) Patients Treated With Luspatercept: Phase 2 PACE-MDS Study,” 23rd European Hematology Association Congress, Jun. 14-17,…
[cited by applicant]
Platzbecker et al., “Mutational Profile and Analysis of Lower-Risk Myelodysplastic Syndromes (MDS) Patients Treated with Luspatercept: Phase 2 PACE-MDS Study,” American Society of Hematology (ASH) 59th Annual Meeting & …
[cited by applicant]
Platzebecker et al., “Erythropoietic cellular analyses in luspatercept-treated lower-risk myelodysplastic syndromes (MDS): Phase 2 PACE-MDS study,” 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Jun. …
[cited by applicant]
Raftopoulos et al., “Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic r…
[cited by applicant]
Ruckle et al., “Single-Dose, Randomized, Double-Blind, Placebo-Controlled Study of ACE-011 (ActRIIA-IgG1) in Postmenopausal Women,” J Bone Mineral Res. 24(4):744-752 (2009).
[cited by applicant]
Sako et al., “Characterization of the ligand binding functionality of the extracellular domain of activin receptor Type IIb,” J Biol Chem. 285(27):21037-48 (2010).
[cited by applicant]
Sanchez et al., “Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice,” PLoS One. 10(10):e0140521 (2015) (14 pages).
[cited by applicant]
Sherman et al., “Multiple-Dose, Safety, Pharmacokinetic, and Pharmacodynamic Study of Sotatercept (ActRIIA-IgGI), a Novel Erythropoietic Agent, in Healthy Postmenopausal Women,” J Clin Pharmacol. 53(11):1121-1130 (2013).
[cited by applicant]
Smith et al., “Long-term Effects of Sotatercept Compared With Placebo for Correction of Anemia in Hemodialysis Subjects: Interim Analysis of ACE-011-REN-001,” 52nd ERA-EDTA Congress, May 28-31, London, UK, Poster FP661,…
[cited by applicant]
Smith et al., “Quantitative Computed Tomography Results for Bone Mass and Abdominal Aortic Vascular Calcification in Hemodialysis Subjects Treated With Escalating Dose Levels of Sotatercept: Interim Analysis of ACE-011-…
[cited by applicant]
Sunada, “Anti-myostatin antibody therapy for myopathies,” Clin Neurol. 51:1157-1159 (2011) (3 pages) (English abstract included).
[cited by applicant]
Sunada, “Myostatin Blockade Therapy for Muscular Atrophy,” Brain Nerve. 63(11):1271-7 (2011) (Abstract only) (2 pages).
[cited by applicant]
Suragani et al., “Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine beta-thalassemia,” Blood. 123(25):3864-3872 (2014).
[cited by applicant]
Suragani et al., “Modified ActRIIB-Fc Fusion Protein (ACE-536) Decreases Irreversible Sickle Cells in a Murine Model of Sickle Cell Disease,” EHA, Poster P535, retrieved from <acceleronpharma.com/wp-content/uploads/2017…
[cited by applicant]
Suragani et al., “Modified ActRIIB-mFc Fusion Protein (murine ortholog of Luspatercept) Mitigates Sickling and Red Cell Pathology in a Murine Model of Sickle Cell Disease,” ASH 56th Annual Meeting, Dec. 6-9, San Francis…
[cited by applicant]
Suragani et al., “Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis,” Nat Med. 20(4):408-414 (2014) (10 pages).
[cited by applicant]
Thevis et al., “Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis—Potential implications for sports drug testing programs,” Rapid Commun Mass Spectrom. 30(5):635-51 (2016).
[cited by applicant]
Tomillero et al., “Gateways to Clinical Trials,” Methods Find Exp Clin Pharmacol. 32(1):47-86 (2010).
[cited by applicant]
Townson et al., “Specificity and Structure of a High Affinity Activin Receptor-like Kinase 1 (ALK1) Signaling Complex,” J Biol Chem. 287(33):27313-27325 (2012).
[cited by applicant]
Vallet et al., “Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease,” Proc Nat Acad Sci. 107(11):5124-9 (2010).
[cited by applicant]
Wagner et al., “Loss of myostatin attenuates severity of muscular dystrophy in mdx mice,” Ann Neurol. 52(6):832-6 (2002).
[cited by applicant]
Wang et al., “A soluble activin receptor Type IIB does not improve blood glucose in streptozotocin-treated mice,” Int J Biol Sci. 11(2):199-208 (2015).
[cited by applicant]
Wang et al., “Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell activation,” J Physiol. 590(9):2151-65 (2012).
[cited by applicant]
Wells, “Additivity of mutational effects in proteins,” Biochemistry. 29(37):8509-17 (1990).
[cited by applicant]
Wolfman et al., “Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases,” Proc Nat Acad Sci. 100(26):15842-6 (2003).
[cited by applicant]
Yee et al., “Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma,” Headache. 1:0 (2015) (1 page).
[cited by applicant]
Yung et al., “ACTRIIA-Fc rebalances BMP and activin/TGF-beta signaling to attenuate experimental pulmonary hypertension,” American Heart Association Scientific Session, Nov. 11-15, Anaheim, CA, retrieved from <acceleron…
[cited by applicant]
Yung, “ACTRIIA-Fc Rebalances Activin/GDF and BMP9 Signaling to Attenuate Experimental Pulmonary Hypertension,” American Heart Association Scientific Session, Nov. 10-12, Chicago, Illinois, retrieved from <acceleronpharm…
[cited by applicant]
Zimmers et al., “Induction of Cachexia in Mice by Systemically Administered Myostatin,” Science. 296(5572):1486-8 (2002) (4 pages).
[cited by applicant]
Campbell et al., “Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial,” Muscle Nerve. 55(4):458-464 (Apr. 2017).
[cited by applicant]
Cappellini et al., “The BELIEVE Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept in Adult Beta-Thalassemia Patients Who Require Regular Red Blood Cell (RBC) Transfusions,” …
[cited by applicant]
Fenaux et al., “Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes,” N Engl J Med. 382(2):140-151 (Jan. 2020).
[cited by applicant]
Goh et al., “Activin receptor type 2A (ACVR2A) functions directly in osteoblasts as a negative regulator of bone mass,” J Biol Chem. 292(33):13809-13822 (Jun. 2017).
[cited by applicant]
Nagy et al., “Electrical impedance myography as a biomarker of myostatin inhibition with ActRIIB-mFc: a study in wild-type mice,” Future Sci OA. 04(06):FSO308 (Apr. 2018) (10 pages).
[cited by applicant]
Piga et al., “Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia,” Blood. 133(12):1279-1289 (Mar. 2019).
[cited by applicant]
Platzbecker et al., “Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study,” Lanc…
[cited by applicant]
Porter et al., “Effects of Luspatercept on Iron Overload and Impact on Responders to Luspatercept: Results from the BELIEVE Trial,” 61st Annual Meeting of the American Society of Hematology (ASH), Abstract 2245, Blood. …
[cited by applicant]
Viprakasit et al., “Evaluating Luspatercept Responders in the Phase 3, Randomized, Double-Blind, Placebo-Controlled BELIEVE Trial of Luspatercept in Adult beta-Thalassemia Patients Who Require Regular Red Blood Cell Tra…
[cited by applicant]
Yu, “Sotatercept for rebalancing BMP/TGF-beta/activin signaling in PAH,” Scientific Sessions Presentation (Nov. 2018) (12 pages).
[cited by applicant]
“Hybrid human mutant activin IIB receptor hu-ActRIIB-ECD, SEQ ID 114.”, retrieved from EBI accession No. GSP:BDH87204, dated Dec. 15, 2016 (1 page).
[cited by applicant]
“Human ActRII extracellular region chimera, SEQ ID 174.”, retrieved from EBI accession No. GSP:BKX55865, dated May 19, 2022 (1 page).
[cited by applicant]
Lema et al., “KER-050, a novel muscle anabolic, functions as a ligand trap that binds myo-catabolic TGFβ ligands and has reduced binding affinity for BMP9, a critical vascular remodeling ligand,” Neuromuscular Disorders…
[cited by applicant]
Morrell et al., “Targeting BMP signalling in cardiovascular disease and anaemia,” Nat Rev Cardiol. 13(2):106-20 (with supplemental material) (2016) (32 pages).
[cited by applicant]
Paddock and O'Meara, “Steps toward therapeutically targeting the activin type Il receptor for treating heart failure,” Am J Physiol Heart Circ Physiol. 318:H326-H328 (Jan. 2020) (3 pages).
[cited by applicant]
Roh et al., “Activin type II receptor signaling in cardiac aging and heart failure,” Sci. Transl. Med. 11, eaau8680 (Mar. 2019) (15 pages).
[cited by applicant]
Hardy et al., “The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology,” Immunology and Cell Biology 93:567-574 (Mar. 2015) (8 pages).
[cited by applicant]
Farrell et al., “Bisphosphonate conjugation for bone specific drug targeting,” Bone Reports 9:47-60 (Jul. 2018) (14 pages).
[cited by applicant]
Fabre et al., “Anti-Sclerostin Antibodies in Osteoporosis and Other Bone Diseases,” J. Clin. Med. 9, 3439 (Oct. 2020) (16 pages).
[cited by applicant]
Ralston and Gaston, “Management of Osteogenesis Imperfecta,” Frontier in Endocrinology 10, 924 (Feb. 2020) (10 pages).
[cited by applicant]
Jiang et al. “Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices,” Frontiers in Cell and Developmental Biology 9, 660316 (May 2021) (11 pages).
[cited by applicant]
Cited By (1)