Extract from the Register of European Patents

EP About this file: EP3785728

EP3785728 - USE OF MYOSTATIN INHIBITORS AND COMBINATION THERAPIES [Right-click to bookmark this link]
StatusExamination is in progress
Status updated on  15.03.2024
Database last updated on 08.04.2026
FormerRequest for examination was made
Status updated on  05.11.2021
FormerThe application has been published
Status updated on  29.01.2021
Most recent event   Tooltip02.04.2026New entry: Renewal fee paid 
Applicant(s)For all designated states
Scholar Rock, Inc.
301 Binney Street, 3rd Floor
Cambridge, MA 02142 / US
[2021/20]
Former [2021/09]For all designated states
Scholar Rock, Inc.
620 Memorial Drive, 2nd Floor
Cambridge, MA 02139 / US
Inventor(s)01 / LONG, Kimberly
2 Jamaica Place
Boston, MA 02130 / US
02 / DONOVAN, Adriana
36 Maxfield Street
West Roxbury, MA 02132 / US
03 / CHYUNG, Yung
2521 Massachusetts Avenue
Lexington, MA 02421 / US
04 / STRAUB, Michelle
346 Hillside Street
Yarmouth, ME 04096 / US
 [2021/09]
Representative(s)Carpmaels & Ransford LLP
One Southampton Row
London WC1B 5HA / GB
[N/P]
Former [2021/09]Marshall, Cameron John
Carpmaels & Ransford LLP
One Southampton Row
London WC1B 5HA / GB
Application number, filing date20179533.313.06.2017
[2021/09]
Priority number, dateUS201662349596P13.06.2016         Original published format: US 201662349596 P
US201762470157P10.03.2017         Original published format: US 201762470157 P
US201762486934P18.04.2017         Original published format: US 201762486934 P
US201762511702P26.05.2017         Original published format: US 201762511702 P
US201762512254P30.05.2017         Original published format: US 201762512254 P
[2021/09]
Filing languageEN
Procedural languageEN
PublicationType: A2 Application without search report 
No.:EP3785728
Date:03.03.2021
Language:EN
[2021/09]
Type: A3 Search report 
No.:EP3785728
Date:28.04.2021
Language:EN
[2021/17]
Search report(s)(Supplementary) European search report - dispatched on:EP31.03.2021
ClassificationIPC:A61K39/00, A61P21/00, C07K16/22
[2021/09]
CPC:
A61K39/3955 (EP,IL,US); A61K31/7105 (IL); C07K16/22 (EP,IL,KR,US);
A61K31/501 (EP,IL); A61K31/575 (EP,IL); A61K31/7125 (EP,IL);
A61K45/06 (EP,IL); A61K9/0019 (IL); A61P21/00 (EP,IL,KR,US);
C12N15/113 (IL); A61K2039/505 (EP,IL,KR,US); A61K2039/54 (KR);
A61K2300/00 (IL); C07K2317/24 (EP,IL,KR,US); C07K2317/33 (EP,IL,KR,US);
C07K2317/567 (EP,IL,KR,US); C07K2317/76 (EP,IL,KR,US); C07K2317/92 (EP,IL,KR,US);
C07K2317/94 (EP,IL,KR,US) (-)
C-Set:
A61K31/501, A61K2300/00 (US,EP);
A61K31/575, A61K2300/00 (US,EP);
A61K31/7125, A61K2300/00 (US,EP);
A61K39/3955, A61K2300/00 (EP,US)
Designated contracting statesAL,   AT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MK,   MT,   NL,   NO,   PL,   PT,   RO,   RS,   SE,   SI,   SK,   SM,   TR [2021/49]
Former [2021/09]AL,  AT,  BE,  BG,  CH,  CY,  CZ,  DE,  DK,  EE,  ES,  FI,  FR,  GB,  GR,  HR,  HU,  IE,  IS,  IT,  LI,  LT,  LU,  LV,  MC,  MK,  MT,  NL,  NO,  PL,  PT,  RO,  RS,  SE,  SI,  SK,  SM,  TR 
TitleGerman:VERWENDUNG VON MYOSTATININHIBITOREN UND KOMBINATIONSTHERAPIEN[2021/09]
English:USE OF MYOSTATIN INHIBITORS AND COMBINATION THERAPIES[2021/09]
French:UTILISATION D'INHIBITEURS DE LA MYOSTATINE ET THÉRAPIES COMBINÉES[2021/09]
Examination procedure28.10.2021Amendment by applicant (claims and/or description)
28.10.2021Examination requested  [2021/49]
28.10.2021Date on which the examining division has become responsible
19.03.2024Despatch of a communication from the examining division (Time limit: M06)
07.10.2024Despatch of communication that the application is deemed to be withdrawn, reason: reply to the communication from the examining division not received in time
09.12.2024Reply to a communication from the examining division
Parent application(s)   TooltipEP17732001.7  / EP3368069
Divisional application(s)EP23157280.1  / EP4218804
Request for further processing for:The application is deemed to be withdrawn due to failure to reply to the examination report
09.12.2024Request for further processing filed
09.12.2024Full payment received (date of receipt of payment)
Request granted
17.12.2024Decision despatched
Fees paidRenewal fee
11.06.2020Renewal fee patent year 03
11.06.2020Renewal fee patent year 04
22.06.2021Renewal fee patent year 05
27.06.2022Renewal fee patent year 06
27.06.2023Renewal fee patent year 07
31.03.2024Renewal fee patent year 08
27.06.2025Renewal fee patent year 09
31.03.2026Renewal fee patent year 10
Opt-out from the exclusive  Tooltip
competence of the Unified
Patent Court
See the Register of the Unified Patent Court for opt-out data
Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court.
Documents cited:Search[YP] WO2016168613  (REGENERON PHARMA et al.)
 [A] WO2016073853  (SCHOLAR ROCK INC et al.)
 [A] WO2013072902  (BHASIN SHALENDER et al.)
 [Y]   ZHIHUA FENG ET AL: "Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset", HUMAN MOLECULAR GENETICS, vol. 25, no. 5, 1 March 2016 (2016-03-01), gb, pages 964 - 975, XP055403595, ISSN: 0964-6906, DOI: 10.1093/hmg/ddv629

DOI:   http://dx.doi.org/10.1093/hmg/ddv629
 [Y]   ESTHER LATRES ET AL: "Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice", SKELETAL MUSCLE, BIOMED CENTRAL LTD, LONDON, UK, vol. 5, no. 1, 9 October 2015 (2015-10-09), pages 34, XP021230308, ISSN: 2044-5040, DOI: 10.1186/S13395-015-0060-8

DOI:   http://dx.doi.org/10.1186/s13395-015-0060-8
 [A]   ROSAMUND C. SMITH ET AL: "Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders", CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE, vol. 7, no. 4, 1 November 2013 (2013-11-01), pages 352 - 360, XP055254846, ISSN: 1751-4258, DOI: 10.1097/SPC.0000000000000013

DOI:   http://dx.doi.org/10.1097/SPC.0000000000000013
 [A]   D'YDEWALLE CONSTANTIN ET AL: "Spinal Muscular Atrophy Therapeutics: Where do we Stand?", NEUROTHERAPEUTICS, ELSEVIER INC, US, vol. 12, no. 2, 29 January 2015 (2015-01-29), pages 303 - 316, XP035490061, ISSN: 1933-7213, [retrieved on 20150129], DOI: 10.1007/S13311-015-0337-Y

DOI:   http://dx.doi.org/10.1007/s13311-015-0337-y
 [A]   CHARLOTTE J. SUMNER ET AL: "Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice", HUMAN MOLECULAR GENETICS, vol. 18, no. 17, 28 May 2009 (2009-05-28), gb, pages 3145 - 3152, XP055402708, ISSN: 0964-6906, DOI: 10.1093/hmg/ddp253

DOI:   http://dx.doi.org/10.1093/hmg/ddp253
 [A]   XIN ZHAO ET AL: "Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy", HUMAN MOLECULAR GENETICS, vol. 25, no. 10, 29 February 2016 (2016-02-29), gb, pages 1885 - 1899, XP055403687, ISSN: 0964-6906, DOI: 10.1093/hmg/ddw062

DOI:   http://dx.doi.org/10.1093/hmg/ddw062
 [A]   V. J. DALBO ET AL: "Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle", ANDROLOGIA., vol. 49, no. 3, 1 June 2016 (2016-06-01), DE, pages e12622, XP055421843, ISSN: 0303-4569, DOI: 10.1111/and.12622

DOI:   http://dx.doi.org/10.1111/and.12622
 [A]   STEPHANIE MOSLER ET AL: "The anabolic steroid methandienone targets the hypothalamic-pituitary-testicular axis and myostatin signaling in a rat training model", ARCHIVES OF TOXICOLOGY, SPRINGER-VERLAG, BERLIN, DE, vol. 86, no. 1, 5 August 2011 (2011-08-05), pages 109 - 119, XP019995015, ISSN: 1432-0738, DOI: 10.1007/S00204-011-0740-Z

DOI:   http://dx.doi.org/10.1007/s00204-011-0740-z
 [T]   LONG KIMBERLY K ET AL: "Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy", HUMAN MOLECULAR GENETICS, vol. 28, no. 7, 27 November 2018 (2018-11-27), pages 1076 - 1089, XP055788244, ISSN: 0964-6906, Retrieved from the Internet DOI: 10.1093/hmg/ddy382

DOI:   http://dx.doi.org/10.1093/hmg/ddy382
by applicantUS2009031435
 US8399437
 US6291158
 US6582915
 US6593081
 US6172197
 US6696245
 JP2015006323
 US2015059468
 US2016052014
 WO2016073879
   DOWDYWEARDEN: "Statistics for Research", 1983, JOHN WILEY & SONS
   PATIL ET AL., AAPS J., vol. 7, no. 1, 2005, pages E61 - E77
   GASCON ET AL., NON-VIRAL DELIVERY SYSTEMS IN GENE THERAPY, 2013
   SOMIARI ET AL., MOLECULAR THERAPY, vol. 2, no. 3, 2000, pages 178 - 187
   HERWEIJER, H.J. A. WOLFF, GENE THERAPY, vol. 10, no. 6, 2003, pages 453 - 458
   NAYEROSSADAT ET AL., ADVANCED BIOMEDICAL RESEARCH, vol. 1, no. 2, 2012, pages 1 - 11
   GLANZMAN AMMAZZONE EMAIN MPELLICCIONI MWOOD JSWOBODA KJSCOTT CPANE MMESSINA SBERTINI E: "The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability", NEUROMUSCUL DISORD., vol. 20, no. 3, March 2010 (2010-03-01), pages 155 - 61, XP026965893
   S. SCHIAFFINO, J. MUSCLE RES. CELL. MOTIL., vol. 10, 1989, pages 197 - 205
   LEROY-WILLIG, MAGNETIC RESONANCE IMAGING, vol. 15, no. 7, 1997, pages 737 - 744
   GAETA, SKELETAL RADIOL
   STANFORD ET AL., J CLIN INVEST., vol. 123, no. 1, 2013, pages 215 - 223
   HARMS ET AL., NATURE MEDICINE., vol. 19, no. 10, 2013, pages 1252 - 63
   MOKDAD ET AL., JAMA: THE JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, vol. 289, no. 1, 2001, pages 76 - 9
   KOBAYASHI ET AL., PLOS ONE, vol. 8, no. 4, 2013, pages e60113
   T. AWANOJ. K. KIMU. R. MONANI: "Spinal muscular atrophy: journeying from bench to bedside", NEUROTHERAPEUTICS, vol. 11, 2014, pages 786 - 795
   U. R. MONANI: "Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease", NEURON, vol. 48, 2005, pages 885 - 896
   L. A. NASHJ. K. BURNSJ. W. CHARDONR. KOTHARYR. J. PARKS: "Spinal Muscular Atrophy: More than a Disease of Motor Neurons?", CURR MOL MED, 2016
   R. FINKELE. BERTINIF. MUNTONIE. MERCURI: "209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy", vol. 25, 7 November 2014, E. S. W. S. GROUP, article "Neuromuscul Disord", pages: 593 - 602
   S. LEFEBVRE ET AL.: "Identification and characterization of a spinal muscular atrophy-determining gene", CELL, vol. 80, 1995, pages 155 - 165
   U. R. MONANI ET AL.: "A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2", HUM MOL GENET, vol. 8, 1999, pages 1177 - 1183, XP002542964, DOI: 10.1093/hmg/8.7.1177

DOI:   http://dx.doi.org/10.1093/hmg/8.7.1177
   K. K. LINGR. M. GIBBSZ. FENGC. P. KO: "Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy", HUM MOL GENET, vol. 21, 2012, pages 185 - 195, XP055574876, DOI: 10.1093/hmg/ddr453

DOI:   http://dx.doi.org/10.1093/hmg/ddr453
   D. W. HAMMERS ET AL.: "Supraphysiological levels of GDF11 induce striated muscle atrophy", EMBO MOL MED, 2017, pages 341 - 356
   F. S. LOFFREDO ET AL.: "Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy", CELL, vol. 153, 2013, pages 828 - 839, XP055562299, DOI: 10.1016/j.cell.2013.04.015

DOI:   http://dx.doi.org/10.1016/j.cell.2013.04.015
   K. J. SWOBODA ET AL.: "Natural history of denervation in SMA: relation to age, SMN2 copy number, and function", ANN NEUROL, vol. 57, 2005, pages 704 - 712
   J. G. BOYER ET AL.: "Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy", HUM MOL GENET, vol. 23, 2014, pages 4249 - 4259
   M. HAYHURSTA. K. WAGNERM. CERLETTIA. J. WAGERSL. L. RUBIN: "A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of survival of motor neuron protein", DEV BIOL, vol. 368, 2012, pages 323 - 334, XP028433463, DOI: 10.1016/j.ydbio.2012.05.037

DOI:   http://dx.doi.org/10.1016/j.ydbio.2012.05.037
   C. CIFUENTES-DIAZ ET AL.: "Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy", J CELL BIOL, vol. 152, 2001, pages 1107 - 1114
   C. A. MUTSAERS ET AL.: "Reversible molecular pathology of skeletal muscle in spinal muscular atrophy", HUM MOL GENET, vol. 20, 2011, pages 4334 - 4344
   M. A. PASSINI ET AL.: "CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy", J CLIN INVEST, vol. 120, 2010, pages 1253 - 1264, XP055040159, DOI: 10.1172/JCI41615

DOI:   http://dx.doi.org/10.1172/JCI41615
   A. N. CALDERE. J. ANDROPHYK. J. HODGETTS: "Small Molecules in Development for the Treatment of Spinal Muscular Atrophy", J MED CHEM, vol. 59, 2016, pages 10067 - 10083, XP055340213, DOI: 10.1021/acs.jmedchem.6b00670

DOI:   http://dx.doi.org/10.1021/acs.jmedchem.6b00670
   N. A. NARYSHKIN ET AL.: "Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy", SCIENCE, vol. 345, 2014, pages 688 - 693
   J. PALACINO ET AL.: "SMN2 splice modulators enhance Ul-pre-mRNA association and rescue SMA mice", NAT CHEM BIOL, vol. 11, 2015, pages 511 - 517, XP055520469, DOI: 10.1038/nchembio.1837

DOI:   http://dx.doi.org/10.1038/nchembio.1837
   H. RATNI ET AL.: "Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy", J MED CHEM, vol. 59, 2016, pages 6086 - 6100, XP055673173, DOI: 10.1021/acs.jmedchem.6b00459

DOI:   http://dx.doi.org/10.1021/acs.jmedchem.6b00459
   Y. HUA ET AL.: "Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model", GENES DEV, vol. 24, 2010, pages 1634 - 1644, XP055038360, DOI: 10.1101/gad.1941310

DOI:   http://dx.doi.org/10.1101/gad.1941310
   Y. HUA ET AL.: "Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model", NATURE, vol. 478, 2011, pages 123 - 126, XP055038358, DOI: 10.1038/nature10485

DOI:   http://dx.doi.org/10.1038/nature10485
   M. A. PASSINI ET AL.: "Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy", SCI TRANSL MED, vol. 3, 2011, pages 72ral8
   C. A. CHIRIBOGA ET AL.: "Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy", NEUROLOGY, vol. 86, 2016, pages 890 - 897
   R. S. FINKEL ET AL.: "Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study", LANCET, vol. 388, 2016, pages 3017 - 3026, XP029849269, DOI: 10.1016/S0140-6736(16)31408-8

DOI:   http://dx.doi.org/10.1016/S0140-6736(16)31408-8
   FDA, NUSINERSEN, OFFICE OF DRUG EVALUATION DECISIONAL MEMORANDUM, 2016
   Z. FENG ET AL.: "Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset", HUM MOL GENET, vol. 25, 2016, pages 964 - 975, XP055403595, DOI: 10.1093/hmg/ddv629

DOI:   http://dx.doi.org/10.1093/hmg/ddv629
   A. M. GLANZMAN ET AL.: "Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III", J CHILD NEUROL, vol. 26, 2011, pages 1499 - 1507
   P. KAUFMANN ET AL.: "Observational study of spinal muscular atrophy type 2 and 3: functional outcomes over 1 year", ARCH NEUROL, vol. 68, 2011, pages 779 - 786
   A. C. MCPHERRONA. M. LAWLERS. J. LEE: "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member", NATURE, vol. 387, 1997, pages 83 - 90
   S. J. LEEA. C. MCPHERRON: "Regulation of myostatin activity and muscle growth", PROC NATL ACAD SCI U S A, vol. 98, 2001, pages 9306 - 9311
   E. LATRES ET AL.: "Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice", SKELET MUSCLE, vol. 5, 2015, pages 34, XP021230308, DOI: 10.1186/s13395-015-0060-8

DOI:   http://dx.doi.org/10.1186/s13395-015-0060-8
   R. C. SMITH ET AL.: "Myostatin Neutralization Results in Preservation of Muscle Mass and Strength in Preclinical Models of Tumor-Induced Muscle Wasting", MOL CANCER THER, vol. 14, 2015, pages 1661 - 1670, XP055328631, DOI: 10.1158/1535-7163.MCT-14-0681

DOI:   http://dx.doi.org/10.1158/1535-7163.MCT-14-0681
   J. WANGX. WANGW. FENG: "Reloading Promotes Recovery of Disuse Muscle Loss by Inhibiting TGFbeta Pathway Activation in Rats After Hind Limb Suspension", AM J PHYS MED REHABIL, 2016
   X. ZHOU ET AL.: "Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival", CELL, vol. 142, 2010, pages 531 - 543, XP028931172, DOI: 10.1016/j.cell.2010.07.011

DOI:   http://dx.doi.org/10.1016/j.cell.2010.07.011
   A. C. MCPHERRONS. J. LEE: "Double muscling in cattle due to mutations in the myostatin gene", PROC NATL ACAD SCI U S A, vol. 94, 1997, pages 12457 - 12461
   D. S. MOSHER ET AL.: "A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs", PLOS GENET, vol. 3, 2007, pages e79, XP002558302, DOI: 10.1371/journal.pgen.0030079

DOI:   http://dx.doi.org/10.1371/journal.pgen.0030079
   M. SCHUELKE ET AL.: "Myostatin mutation associated with gross muscle hypertrophy in a child", N ENGL J MED, vol. 350, 2004, pages 2682 - 2688, XP008143232, DOI: 10.1056/NEJMoa040933

DOI:   http://dx.doi.org/10.1056/NEJMoa040933
   K. GARBER: "No longer going to waste", NAT BIOTECHNOL, vol. 34, 2016, pages 458 - 461
   A. A. AMATO ET AL.: "Treatment of sporadic inclusion body myositis with bimagrumab", NEUROLOGY, vol. 83, 2014, pages 2239 - 2246, XP055251705, DOI: 10.1212/WNL.0000000000001070

DOI:   http://dx.doi.org/10.1212/WNL.0000000000001070
   C. BECKER ET AL.: "Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial", LANCET DIABETES ENDOCRINOL, vol. 3, 2015, pages 948 - 957
   C. 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, 2016
   J. R. MENDELL ET AL.: "A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy", MOL THER, vol. 23, 2015, pages 192 - 201, XP002752989, DOI: 10.1038/mt.2014.200

DOI:   http://dx.doi.org/10.1038/mt.2014.200
   K. R. WAGNER ET AL.: "A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy", ANN NEUROL, vol. 63, 2008, pages 561 - 571, XP002514515, DOI: 10.1002/ana.21338

DOI:   http://dx.doi.org/10.1002/ana.21338
   S. J. LEE ET AL.: "Regulation of muscle growth by multiple ligands signaling through activin type II receptors", PROC NATL ACAD SCI U S A, vol. 102, 2005, pages 18117 - 18122
   A. L. SCHNEYER ET AL.: "Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin", ENDOCRINOLOGY, vol. 149, 2008, pages 4589 - 4595
   M. A. EGERMAN ET AL.: "GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration", CELL METAB, vol. 22, 2015, pages 164 - 174, XP055563308, DOI: 10.1016/j.cmet.2015.05.010

DOI:   http://dx.doi.org/10.1016/j.cmet.2015.05.010
   A. F. ESQUELAS. J. LEE: "Regulation of metanephric kidney development by growth/differentiation factor 11", DEV BIOL, vol. 257, 2003, pages 356 - 370
   J. KIM ET AL.: "GDF11 controls the timing of progenitor cell competence in developing retina", SCIENCE, vol. 308, 2005, pages 1927 - 1930, XP003006667, DOI: 10.1126/science.1110175

DOI:   http://dx.doi.org/10.1126/science.1110175
   A. C. MCPHERRONA. M. LAWLERS. J. LEE: "Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11", NAT GENET, vol. 22, 1999, pages 260 - 264
   H. H. WU ET AL.: "Autoregulation of neurogenesis by GDF11", NEURON, vol. 37, 2003, pages 197 - 207
   M. SINHA ET AL.: "Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle", SCIENCE, vol. 344, 2014, pages 649 - 652, XP055316964, DOI: 10.1126/science.1251152

DOI:   http://dx.doi.org/10.1126/science.1251152
   R. WIJAYARATHNAD. M. DE KRETSER: "Activins in reproductive biology and beyond", HUM REPROD UPDATE, vol. 22, 2016
   E. LACH-TRIFILIEFF ET AL.: "An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy", MOL CELL BIOL, vol. 34, 2014, pages 606 - 618, XP055254997, DOI: 10.1128/MCB.01307-13

DOI:   http://dx.doi.org/10.1128/MCB.01307-13
   K. T. MURPHY ET AL.: "Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function", FASEB J, vol. 24, 2010, pages 4433 - 4442
   B. C. YADEN ET AL.: "Follistatin: a novel therapeutic for the improvement of muscle regeneration", J PHARMACOL EXP THER, vol. 349, 2014, pages 355 - 371, XP055240847, DOI: 10.1124/jpet.113.211169

DOI:   http://dx.doi.org/10.1124/jpet.113.211169
   P. SINGHH. RONGT. GORDIJ. BOSLEYI. BHATTACHARYA: "Translational Pharmacokinetic/Pharmacodynamic Analysis of MYO-029 Antibody for Muscular Dystrophy", CLIN TRANSL SCI, vol. 9, 2016, pages 302 - 310
   L. WOODHOUSE ET AL.: "A Phase 2 Randomized Study Investigating the Efficacy and Safety of Myostatin Antibody LY2495655 versus Placebo in Patients Undergoing Elective Total Hip Arthroplasty", J FRAILTY AGING, vol. 5, 2016, pages 62 - 70
   P. BALAGOPALO. E. ROOYACKERSD. B. ADEYP. A. ADESK. S. NAIR: "Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans", AM J PHYSIOL, vol. 273, 1997, pages E790 - 800
   S. W. LAMBERTSA. W. VAN DEN BELDA. J. VAN DER LELY: "The endocrinology of aging", SCIENCE, vol. 278, 1997, pages 419 - 424
   S. J. LEE: "Extracellular Regulation of Myostatin: A Molecular Rheostat for Muscle Mass", IMMUNOL ENDOCR METAB AGENTS MED CHEM, vol. 10, 2010, pages 183 - 194
   N. M. WOLFMAN ET AL.: "Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases", PROC NATL ACAD SCI U S A, vol. 100, 2003, pages 15842 - 15846, XP008049722, DOI: 10.1073/pnas.2534946100

DOI:   http://dx.doi.org/10.1073/pnas.2534946100
   H. Q. HANX. ZHOUW. E. MITCHA. L. GOLDBERG: "Myostatin/activin pathway antagonism: molecular basis and therapeutic potential", INT J BIOCHEM CELL BIOL, vol. 45, 2013, pages 2333 - 2347, XP028699813, DOI: 10.1016/j.biocel.2013.05.019

DOI:   http://dx.doi.org/10.1016/j.biocel.2013.05.019
   S. B. ANDERSONA. L. GOLDBERGM. WHITMAN: "Identification of a novel pool of extracellular pro-myostatin in skeletal muscle", J BIOL CHEM, vol. 283, 2008, pages 7027 - 7035, XP055100146, DOI: 10.1074/jbc.M706678200

DOI:   http://dx.doi.org/10.1074/jbc.M706678200
   H. R. BERGEN ET AL.: "Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay", SKELET MUSCLE, vol. 5, 2015, pages 21, XP055588350, DOI: 10.1186/s13395-015-0047-5

DOI:   http://dx.doi.org/10.1186/s13395-015-0047-5
   G. SENGLER. N. ONOT. SASAKIL. Y. SAKAI: "Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: extracellular matrix interactions and growth factor bioavailability", J BIOL CHEM, vol. 286, 2011, pages 5087 - 5099
   T. A. ZIMMERS ET AL.: "Induction of cachexia in mice by systemically administered myostatin", SCIENCE, vol. 296, 2002, pages 1486 - 1488, XP009102899, DOI: 10.1126/science.1069525

DOI:   http://dx.doi.org/10.1126/science.1069525
   J. R. APGAR ET AL.: "Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody", MABS, vol. 8, 2016, pages 1302 - 1318, XP055416065, DOI: 10.1080/19420862.2016.1215786

DOI:   http://dx.doi.org/10.1080/19420862.2016.1215786
   T. T. LE ET AL.: "SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN", HUM MOL GENET, vol. 14, 2005, pages 845 - 857, XP008073633, DOI: 10.1093/hmg/ddi078

DOI:   http://dx.doi.org/10.1093/hmg/ddi078
   X. ZHAO ET AL.: "Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy", HUM MOL GENET, vol. 25, 2016, pages 1885 - 1899, XP055403687, DOI: 10.1093/hmg/ddw062

DOI:   http://dx.doi.org/10.1093/hmg/ddw062
   M. LIUD. W. HAMMERSE. R. BARTONH. L. SWEENEY: "Activin Receptor Type IIB Inhibition Improves Muscle Phenotype and Function in a Mouse Model of Spinal Muscular Atrophy", PLOS ONE, vol. 11, 2016, pages e0166803, XP055403589, DOI: 10.1371/journal.pone.0166803

DOI:   http://dx.doi.org/10.1371/journal.pone.0166803
   H. FUNAKOSHI ET AL.: "Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons", SCIENCE, vol. 268, 1995, pages 1495 - 1499
   C. E. HENDERSON ET AL.: "GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle", SCIENCE, vol. 266, 1994, pages 1062 - 1064, XP000612014
   Y. YAMAMOTO ET AL.: "Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons", DEVELOPMENT, vol. 124, 1997, pages 2903 - 2913, XP002918460
   J. YANG ET AL.: "Expression of myostatin pro domain results in muscular transgenic mice", MOL REPROD DEV, vol. 60, 2001, pages 351 - 361, XP002444986, DOI: 10.1002/mrd.1097

DOI:   http://dx.doi.org/10.1002/mrd.1097
   B. ZHAOR. J. WALLJ. YANG: "Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance", BIOCHEM BIOPHYS RES COMMUN, vol. 337, 2005, pages 248 - 255
   V. AUGUSTOPADOVANI, C.R.CAMPOS, G.E.R.: "Skeletal muscle fiber types in C57BL/6 mice", BRAZ. J. MORPHOL. SCI, vol. 21, 2004, pages 89 - 94
   J. M. EASONG. A. SCHWARTZG. K. PAVLATHA. W. ENGLISH: "Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter", J APPL PHYSIOL, vol. 89, 1985, pages 251 - 258
   Z. A. GRAHAM ET AL.: "A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury", J NEUROTRAUMA, vol. 33, 2016, pages 1128 - 1135
The EPO accepts no responsibility for the accuracy of data originating from other authorities; in particular, it does not guarantee that it is complete, up to date or fit for specific purposes.