Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Compositions for making and using anti-Myostatin antibodies

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Publication Date:
    March 12, 2024
  • Additional Information
    • Patent Number:
      11925,683
    • Appl. No:
      17/446897
    • Application Filed:
      September 03, 2021
    • Abstract:
      Aspects of the present disclosure relate to antibodies that specifically bind proMyostatin and/or latent Myostatin and uses thereof.
    • Inventors:
      SCHOLAR ROCK, INC. (Cambridge, MA, US)
    • Assignees:
      Scholar Rock, Inc. (Cambridge, MA, US)
    • Claim:
      1. A host cell comprising a polynucleotide encoding an antibody or antigen-binding fragment thereof that specifically binds to pro/latent myostatin, binds to pro/latent myostatin with a decreased affinity at an acidic pH as compared to a neutral or physiological pH, and inhibits myostatin signaling after binding, wherein the host cell is prepared by the steps of: (i) screening for an antibody or antigen-binding fragment that specifically binds to pro/latent myostatin as compared to mature myostatin and/or another member of the transforming growth factor beta family; (ii) screening the antibody or antigen-binding fragment thereof for inhibition of myostatin signaling; (iii) assaying the antibody or antigen-binding fragment for binding to pro/latent myostatin wherein the antibody or fragment binds to pro/latent myostatin with a decreased affinity at an acidic pH as compared to a neutral or physiological pH; (iv) isolating a polynucleotide encoding the antibody or antigen-binding fragment; and (v) incorporating the polynucleotide in the host cell.
    • Claim:
      2. The host cell of claim 1 , wherein the host cell is a mammalian cell.
    • Claim:
      3. The host cell of claim 1 , wherein the host cell is a NSO cell, a HEK293 cell, or a CHO cell.
    • Claim:
      4. The host cell of claim 1 , wherein step (ii) comprises screening the antibody or antigen-binding fragment thereof using a cell-based assay.
    • Claim:
      5. The host cell of claim 4 , wherein the cell-based assay is a reporter assay.
    • Claim:
      6. The host cell of claim 5 , wherein the reporter assay is a SMAD-based reporter assay.
    • Claim:
      7. A cell line comprising the host cell of claim 1 .
    • Claim:
      8. The cell line of claim 7 , wherein the cell line is a mammalian cell line.
    • Claim:
      9. The cell line of claim 7 , wherein the cell line is a NSO cell line, a HEK293 cell line, or a CHO cell line.
    • Patent References Cited:
      6096506 August 2000 Lee et al.
      6656475 December 2003 Lee et al.
      6858208 February 2005 Lee et al.
      7138501 November 2006 Ruben et al.
      7566768 July 2009 Lee et al.
      10287345 May 2019 Donovan et al.
      10307480 June 2019 Straub et al.
      10751413 August 2020 Carven et al.
      10882904 January 2021 Donovan et al.
      10946036 March 2021 Long et al.
      11135291 October 2021 Straub et al.
      11155611 October 2021 Donovan et al.
      11439704 September 2022 Carven et al.
      20020157126 October 2002 Lee et al.
      20030167492 September 2003 Lee et al.
      20050049402 March 2005 Babcook et al.
      20050143306 June 2005 Junker et al.
      20060025340 February 2006 Knopf et al.
      20060216279 September 2006 Glass et al.
      20060263354 November 2006 Chin et al.
      20070087000 April 2007 Walsh et al.
      20070178095 August 2007 Smith et al.
      20070218067 September 2007 Buttner et al.
      20080119426 May 2008 Dale
      20080213251 September 2008 Sexton et al.
      20080299126 December 2008 Han et al.
      20090131638 May 2009 Davies et al.
      20090148436 June 2009 Lavallie et al.
      20090324590 December 2009 Kambadur et al.
      20100080811 April 2010 Davies et al.
      20100087631 April 2010 Han et al.
      20100166764 July 2010 Sayers et al.
      20100183616 July 2010 Green et al.
      20100221777 September 2010 Choe et al.
      20100331252 December 2010 Hamrick
      20110165175 July 2011 Linhard et al.
      20110239317 September 2011 Lee et al.
      20110256132 October 2011 Ashman et al.
      20110293630 December 2011 Stitt et al.
      20130065820 March 2013 Bower et al.
      20130209489 August 2013 Han et al.
      20130216548 August 2013 Neijssen et al.
      20130230515 September 2013 Han et al.
      20130336982 December 2013 Mader et al.
      20140017262 January 2014 Sanicola-Nadel et al.
      20140023638 January 2014 Lavallie et al.
      20160199458 July 2016 Knopf et al.
      20170198032 July 2017 Donovan et al.
      20170333558 November 2017 Straub et al.
      20210046180 February 2021 Carven et al.
      20210283166 September 2021 Long et al.
      20210332117 October 2021 Donovan et al.
      2011244851 November 2011
      2853898 April 2015
      3922645 December 2021
      2003-520839 July 2003
      2004-504826 February 2004
      2009-545313 December 2009
      2010-502633 January 2010
      2012-520887 September 2012
      2017536354 December 2017
      WO 1996/001845 January 1996
      WO2001-055029 August 2001
      WO 2002/009641 February 2002
      WO 2002/085306 October 2002
      WO 2003/027248 April 2003
      WO 2004/009776 January 2004
      WO 2004/024890 March 2004
      WO 2004/037861 May 2004
      WO 2005/066204 July 2005
      WO 2005/084699 September 2005
      WO 2005/103081 November 2005
      WO 2005/115439 December 2005
      WO 2006/116269 November 2006
      WO 2007/024535 March 2007
      WO 2007/044411 April 2007
      WO 2007/047112 April 2007
      WO 2007/061995 May 2007
      WO 2008/067480 June 2008
      WO 2008/119426 October 2008
      WO 2009/038760 March 2009
      WO 2010/070094 June 2010
      WO 2010/125003 November 2010
      WO 2010/144452 December 2010
      WO 2011/122011 October 2011
      WO 2011/150008 December 2011
      WO 2012/024242 February 2012
      WO 2013/071056 May 2013
      WO 2013/072902 May 2013
      WO 2013/148284 November 2013
      WO 2013/165972 November 2013
      WO 2013/186719 December 2013
      WO 2014/074532 May 2014
      WO 2014/182676 November 2014
      WO 2015/070158 May 2015
      WO 2015/195094 December 2015
      WO 2016/073853 May 2016
      WO 2016/073879 May 2016
      WO 2016/073906 May 2016
      WO 2016/098357 June 2016
      WO 2016/168613 October 2016
      WO 2017/049011 March 2017
      WO 2017/120523 July 2017
      WO 2018/116201 June 2018



























































































































    • Other References:
      Castellana et al, 2011. Proteomics. 11(3): 395-405. cited by examiner
      Chen Declaration filed in opposition of EP Patent No. 3368069 on Apr. 27, 2022 ( 2pgs.). cited by applicant
      Cure SMA Presentation filed in opposition of EP Patent No. 3368069 on Apr. 27, 2022 (86 pgs.). cited by applicant
      Hori et al. (2022) “Elimination of plasma soluble antigen in cynomolgus monkeys by combining pH-dependent antigen binding and novel Fc engineering” MAbs. 14(1):2068213. doi: 10.1080/19420862.2022.2068213. cited by applicant
      Jarecki Declaration filed in opposition of EP Patent No. 3368069 on Apr. 27, 2022 (2 pgs.). cited by applicant
      Jobling et al. (2006) “Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species”, Radiat Res. 166(6):839-48. cited by applicant
      Ling et al. (2012) “Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy” Human Molecular Genetics, vol. 21, No. 1, pp. 185-195. cited by applicant
      Opposition Pre-summons Response filed in EP Patent No. 3368069 on Apr. 27, 2022 (33 pgs.). cited by applicant
      Bernardo et al. (2010) “Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice,” PLoS One. 5(6): e11307. cited by applicant
      Extended European Search Report in EP Application No. 21170667.6 dated Nov. 11, 2021. cited by applicant
      Igawa et al. (2013) “Engineered Monoclonal Antibody with Novel AntigenSweeping Activity In Vivo”. PLoS One 8(5):e63236. cited by applicant
      Schoch et al., (2015) “Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics”, Proceedings of the National Academy of Sciences, vol. 112, No. 19, pp. 5997-6002. cited by applicant
      Anderson et al., (2008) “Identification of a novel pool of extracellular pro myostatin in skeletal muscle”, The Journal of Biological Chemistry, 283(11):7027-7035. cited by applicant
      Anonymous (2005) “Human Myostatin ELISA—Prodomain specific”, BioVendor Laboratory Medicine, Inc., XP055100354, Retrieved from the Internet: URL:http://deltaclon.es/pdf/RD193058100.pdf (10 pgs.). cited by applicant
      Anonymous (2017) “SC 2. Anterolateral Systems—Deficits” [online]. Retrieved from: http://www.neuroanatomy.wisc.edu/sc97/text/p2/deficits.htm; on Jul. 11, 2017 (1 page). cited by applicant
      Anonymous (2019) “GDF-11/BMP-11 Mouse anti-Human, Clone: 743833, R&D Systems(TM)” [online]. Retrieved from: http://www.fishersci.co.uk/shop/products/gdf-11bpm-11-mouse-anti-human-clone-743833-r-d-systems/15724724; on Feb. 28, 2019 (4 pgs.). cited by applicant
      Australian Application No. 202010134, filed Jul. 27, 2020, for Scholar Rock, Inc.: Examination Report No. 1, dated Oct. 15, 2020. cited by applicant
      Baranello et al., (2020) “Evaluation of body composition as a potential biomarker in spinal muscular atrophy”, Muscle & Nerve, 61(4):530-534. cited by applicant
      Benatar (2007) “Lost in translation: Treatment trials in the SOD1 mouse and in human ALS”, Neurobiology of Disease, 26:1-13. cited by applicant
      Biovendor, Research and Diagnostics Products. Myostatin Propeptide Human, Chicken Polyclonal Antibody. Product Data Sheet 2 pgs. Apr. 11, 2013. cited by applicant
      Bräuninger et al., (2003) “Epstein-Barr virus (EBV)-positive lymphoproliferations in post-transplant patients show immunoglobulin V gene mutation patterns suggesting interference of EBV with normal B cell differentiation processes”, Eur J Immunol., 33(6):1593-1602. cited by applicant
      Breitbart et al., (2013) “Highly specific detection of myostatin prodomain by an immunoradiometric sandwich assay in serum of healthy individuals and patients”, PLOS One, 8(11):e80454 (10 pgs.). cited by applicant
      Brown et al., (1996) “Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?”, J Immunol., 156(9):3285-3291. cited by applicant
      Burch et al., (2017) “Reduced serum myostatin concentrations associated with genetic muscle disease progression”, Journal of Neurology, 264(3):541-553. cited by applicant
      Chen et al., “Considerations for Developing Combination Therapies in SMA”, Cure SMA Researcher Meeting, Jun. 16, 2016. cited by applicant
      Ciciliot et al., (2013) “Muscle type and fiber type specificity in muscle wasting”, Int J Biochem Cell Biol., 45(10):2191-2199. cited by applicant
      Cohen et al., (2015) “Muscle wasting in disease: molecular mechanisms and promising therapies”, Nat Rev Drug Discov., 14(1):58-74. cited by applicant
      Cully, (2014) “Beefing up the right splice variant to treat spinal muscular atrophy”. Nat Rev Drug Discov 13, 725. https://doi.org/10.1038/nrd4445 (1 pg.). cited by applicant
      Dagbay et al., (2020) “ Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015”, J. Biol. Chem., 295(16):5404-5418. cited by applicant
      Dalbo et al., (2017) “Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle”, Andrologia, 49(3):1-11. cited by applicant
      Day et al., (2021) “Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial”, Lancet Neurol, 20:284-293. cited by applicant
      Dibernardo et al., (2006) “Translating preclinical insights into effective human trials in ALS”, Biochimica et Biophysica Acta, 1762:1139-1149. cited by applicant
      D'ydewalle et al., (2015) “Spinal muscular atrophy therapeutics: where do we stand?”, Neurotherapeutics, 12(2):303-316. cited by applicant
      Egerman et al., (2015) “GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration”, Cell Metabolism, 22(1):164-174. cited by applicant
      European Patent Application No. 16828657.3, by Scholar Rock, Inc.: Supplementary European Search Report and Opinion, dated Mar. 20, 2019. cited by applicant
      European Patent Application No. 20179533.3, by Scholar Rock, Inc.: Partial European Search Report, dated Mar. 31, 2021 (12 pgs.). cited by applicant
      European Patent Application No. 20193425.4, by Scholar Rock, Inc.: European Search Report, dated Apr. 1, 2021 (9 pgs.). cited by applicant
      Farrar et al. (2017) “Emerging therapies and challenges in spinal muscular atrophy” Ann Neural 81(3): 355-368. Published online Feb. 17, 2017. doi: 10.1002/ana.24864. Publication details included. cited by applicant
      Feng et al., (2016) “Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset”, Human Molecular Genetics, 25(5):964-975. cited by applicant
      Ferrara et al., (2015) “Recombinant renewable polyclonal antibodies”, MAbs, 7(1):32-41. cited by applicant
      Fidler, (2016) “Scholar Rock Rolls Up $36M to Move Muscle Drug to Clinical Trials” https://xconomy.com/boston/2016/01/04/scholar-rock-rolls-up-36m-to-move-muscle-drug-to-clinical-trials/. cited by applicant
      Ge et al., (2005) “GDF11 Forms a Bone Morphogenetic Protein 1-Activated Latent Complex That Can Modulate Nerve Growth Factor-Induced Differentiation of PC12 Cells”, Molecular and Cellular Biology, 25(14):5846-5858. cited by applicant
      Giangregorio et al., (2006) “Bone Loss and Muscle Atrophy in Spinal Cord Injury: Epidemiology, Fracture Prediction, and Rehabilitation Strategies”, J Spinal Cord Med., 29(5):489-500. cited by applicant
      Gogliotti et al., (2011) “Characterization of a commonly used mouse model of SMA reveals increased seizures susceptibility and heightened fear response in FVB/N mice”, Neurobiol Dis. 43(1):142-151. cited by applicant
      Gonzalez et al., (2005) “BMP-1/Tolloid-like Metalloproteases Process Endorepellin, the Angiostatic C-terminal Fragment of Perlecan”, The Journal of Biological Chemistry, 280(8):7080-7087. cited by applicant
      Graham et al., (2015) “A Soluble Myostatin Inhibitor Does Not Prevent Sublesional Muscle Atrophy 56 Days After Spinal Cord Injury in Mice”, Medicine & Science in Sports & Exercise, Abstract No. 2219:587. cited by applicant
      Guo et al., (2009) “Myostatin Inhibition in Muscle, but Not Adippose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity”, PLoS One, 4(3):e4937 (11 pgs.). cited by applicant
      Heymsfield et al., (2021) “Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial”, 4(1):e2033457. doi: 10.1001/jamanetworkopen.2020.33457. cited by applicant
      Holzbaur et al., (2006) “Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis”, Neurobiol Dis., 23(3):697-707. cited by applicant
      Iinternational Search Report for Application No. PCT/US2015/059557, dated May 19, 2016 (5 pgs.). cited by applicant
      International Application No. PCT/US2016/043712, by Scholar Rock, Inc., International Search Report and Written Opinion, dated Jan. 13, 2017. cited by applicant
      International Application No. PCT/US2017/012606, by Scholar Rock, Inc., International Search Report and Written Opinion, dated Jul. 24, 2017. cited by applicant
      International Application No. PCT/US2017/012606, by Scholar Rock, Inc., Written Opinion dated Jan. 3, 2018 (18 pgs.). cited by applicant
      International Application No. PCT/US2017/037332, by Scholar Rock, Inc., International Search Report and Written Opinion, dated Nov. 14, 2017. cited by applicant
      International Application No. PCT/US2018/012686, by Scholar Rock, Inc., International Search Report and Written Opinion, dated Apr. 3, 2018. cited by applicant
      International Preliminary Report on Patentability for Application No. PCT/US2015/059468, dated May 9, 2017 (12 pgs.). cited by applicant
      International Preliminary Report on Patentability for Application No. PCT/US2015/059515, dated May 9, 2017 (12 pgs.). cited by applicant
      International Preliminary Report on Patentability for Application No. PCT/US2015/059557, dated May 9, 2017 (12 pgs.). cited by applicant
      International Preliminary Report on Patentability for Application No. PCT/US2016/052014, dated Mar. 29, 2018 (11 pgs.). cited by applicant
      International Search Report and Written Opinion for Application No. PCT/US2016/052014, dated Jan. 9, 2017 (17 pgs.). cited by applicant
      International Search Report for Application No. PCT/US2015/059468, dated Apr. 4, 2016 (6 pgs.). cited by applicant
      International Search Report for Application No. PCT/US2015/059515, dated Mar. 25, 2016 (8 pgs.). cited by applicant
      Japanese Patent Application No. 2019-517209, filed Jun. 13, 2017, by Scholar Rock, Inc., Decision to Grant a Patent, dated Dec. 8, 2020 (7 pgs.). cited by applicant
      Jarolim et al., (2013) “2013 AACC Annual Meeting Abstracts B-175 Determination of Cardiac Troponin with a Single-Molecule High-Sensitivity Assay and Outcomes in Patients with Stable Coronary Artery Disease: Analysis from PROVE IT-TIMI 22”, XP055100559, Retrieved from the Internet: URL:http://www.aacc.org/events/Annual_Meeting/abstracts/Documents/AACC_ 13_AM_B175-B239.pdf (22 pgs.). cited by applicant
      Jiang et al., (2019) “Genomic analysis of a spinal muscular atrophy (SMA) discordant family identifies a novel mutation in TLL2, an activator of growth differentiation factor 8 (myostatin): a case report”, BMC Medical Genetics, 20(1):204. cited by applicant
      Kariya et al., (2014) “Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation”, The Journal of Clinical Investigation, 124(2):785-800. cited by applicant
      Latres et al., (2015) “Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice”, Skeletal Muscle, 5:34. cited by applicant
      Latres et al., (2017) “Activin A more prominently regulates muscle mass in primates than does GDF8”, Nature Communications, 8:15153. cited by applicant
      Liu et al., (2014) “The Smn-Independent Beneficial Effect of Trichostatin A on an Intermediate Mouse Model of Spinal Muscular Atrophy”, PLOS ONE, 9(7):e101225.(9 pgs.). cited by applicant
      Liu et al., (2016) Activin Receptor Type 118 Inhibition Improves Muscle Phenotype and Function in a Mouse Model of Spinal Muscular Atrophy, PLoS One 11 (11):e0166803, published Nov. 21, 2016. cited by applicant
      Loffredo et al., (2013) “Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy”, Cell, 153(4):828-839. cited by applicant
      Long et al., (2019) “Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy”, Human Molecular Genetics, 28(7):1076-1089. cited by applicant
      Mariot et al., (2017) “Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches”, Nature Communications, 8(1):1859. cited by applicant
      McPherron et al., (2010) “Metabolic Functions of Myostatin and GDF11”, Immunol Endocr Metab Agents Med Chem., 10(4):217-231. cited by applicant
      Morrison et al., (2009) “A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis”, Exp Neurol, 217(2):258-268. cited by applicant
      Mosler et al., (2012) “The anabolic steroid methandienone targets the hypothalamic-pituitary-testicular axis and myostatin signaling in a rat training model”, Archives of Toxicology, 86(1):109-119. cited by applicant
      Muramatsu et al., (2021) “Novel myostatin-specific antibody enhances muscle strength in muscle disease models” , Sci Rep, 11:2160, https://doi.org/10.1038/s41598-021-81669-8 (16 pgs.). cited by applicant
      Naryshkin et al., (2014) “SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy” Science, vol. 345, Issue 6197, pp. 688-693, DOI: 10.1126/science.1250127. cited by applicant
      Ojala et al., (2021) “In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy”, Brain Sci., 11:194 (39 pgs.). cited by applicant
      Opposition filed in EP Patent No. 3368069 on Apr. 28, 2021 (37 pgs.). cited by applicant
      Opposition filed in EP Patent No. 3368069 on May 4, 2021 (89 pgs.). cited by applicant
      Pandya et al., (2013) “Therapeutic neuroprotective agents for amyotrophic lateral sclerosis”, Cell Mol Life Sci., 70(24):4729-4745. cited by applicant
      Pirruccello-Straub et al., (2018) “Blocking extracellular activation of myostatin as a strategy for treating muscle wasting”, Scientific Reports, 8(1):2292. cited by applicant
      Pistilli et al., (2011) “Targeting Activin Type IIB Receptor to Improve Muscle Mass and Function in the mdx Mouse Model of Duchenne Muscular Dystrophy”, Am J Pathol., 178(3):1287-1297. cited by applicant
      Pubchem Substance No. CID 310264710 (trevogrumab); Create Date Feb. 5, 2016 [online]. Retrieved from: http://pubchem.ncbi.nlm.nih.gov/substance/310264710; on Feb. 5, 2020 (6 pgs.). cited by applicant
      Reply to Examination Report dated Feb. 13, 2016 in EP Application No. 17732001.7, dated May 31, 2019. cited by applicant
      Request for early entry and processing of EP Application No. 17732001.7, on Jun. 1, 2018. cited by applicant
      Response to Communication dated Jul. 31, 2018 in EP Application No. 17732001.7, dated Dec. 10, 2018. cited by applicant
      Rodino-Klapac et al., (2009) “Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease” Muscle Nerve 39(3):283-96. doi: 10.1002/mus.21244. cited by applicant
      Roth et al., (2004) “Myostatin: a therapeutic target for skeletal muscle wasting” Curr Opin Clin Nutr Metab Care 7(3):259-63. doi: 10.1097/00075197-200405000-00004. cited by applicant
      ScholarRock Announcement (2015) “Scholar Rock Presents First Data for Niche Modulator Inhibiting Myostatin Activation and Announces SRK-015 as Lead Drug Program” (1 pg.). cited by applicant
      Rose et al., (2009) “Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy” Hum Mol Genet. Mar. 15, 2009; 18(6): 997-1005, Published online Dec. 12, 2008. doi: 10.1093/hmg/ddn426. cited by applicant
      ScholarRock.com (2016) “Scholar Rock discovered SRK-015, a selective and local inhibitor or latent myostatin activation for the treatment of primary myopathies” (1 pg.). cited by applicant
      Sgoutas et al., (1992) “Effect of Lyophilization on Determinations of Lipoprotein(a) in Serum”, Clin Chem., 38(7):1355-1360. cited by applicant
      Shorrock et al., (2016) “Development and Translation of Therapies for Spinal Muscular Atrophy” EMJ Neurol. 4[1]:64-73. cited by applicant
      Singapore Patent Application No. 11201805709R, filed Jan. 6, 2017, by Scholar Rock, Inc.: International Search Report and Written Opinion, dated Oct. 11, 2019 (12 pgs.). cited by applicant
      SMA Annual Conference “The 2016 Annual SMA Conference is here”, https://www.curesma.org/the-2016-annual-sma-conference-is-here/ (3 pgs.). cited by applicant
      SMA Researcher Meeting Summary: The Changing Landscape of SMA 2016 (5 pgs.). cited by applicant
      Smith et al., (2013) “Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders”, Curr Opin Support Palliat Care, 7(4):352-360. cited by applicant
      Smith et al., (2015) “Myostatin Neutralization Results in Preservation of Muscle Mass and Strength in Preclinical Models of Tumor-Induced Muscle Wasting”, Mol Cancer Ther., 14(7): 1661-1670. cited by applicant
      Spinraza (Nusinersen) FDA label, Dec. 2016 (13 pgs.). cited by applicant
      Sumner et al. (2016) “Spinal Muscular Atrophy, Disease Mechanisms and Therapy”, Academic Press, pp. 6, 15-19 and 351-356. Publication details included (22 pgs). cited by applicant
      Sumner et al., (2009) “Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice”, Human Molecular Genetics, 18(17):3145-3152. cited by applicant
      Sumner et al., (2016) “Spinal Muscular Atrophy, Disease Mechanisms and Therapy”, First edition, Academic Press, Chapters 15, 16, 21, and 23. Publication details included (91 pgs.). cited by applicant
      Suragani et al., (2014) “Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis”, Nature Medicine, 20(4):408-414. cited by applicant
      Szlama et al., (2013) “Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2”, FEBS Journal, 280(16):3822-3839. cited by applicant
      Unkown (2000) American Spinal Injury Association (ASIA) Impairment Scale, Standard Neurological Classification of Spinal Cord Injury (2 pgs.). cited by applicant
      Unknown (2013) “Myostatin Propeptide Human, Chicken Polyclonal Antibody”, BioVendor, Research and Diagnostic Products, Data Sheet (2 pgs.). cited by applicant
      Wagner, (2020) “The elusive promise of myostatin inhibition for muscular dystrophy”, Current Opinion in Neurology, 33(5):621-628. cited by applicant
      Walker et al., Biochemistry and Biology of GDF11 and Myostatin: similarities, differences and questions for future investigation, Cir. Res. 118(7): 1125-1142, published Apr. 1, 2016. cited by applicant
      Walter et al., (2021) “Improving Care and Empowering Adults Living with SMA: A Call to Action in the New Treatment Era”, Journal of Neuromuscular Diseases, DOI 10.3233/JND-200611 (9 pgs.). cited by applicant
      Wang (2000) “Lyophilization and development of solid protein pharmaceuticals”, International Journal of Pharmaceutics, 203(1-2):1-60. cited by applicant
      Whittemore et al., (2003) “Inhibition of myostatin in adult mice increases skeletal muscle mass and strength”, Biochem Biophys Res Commun, 300(4):965-971. cited by applicant
      Wintgens et al., (2012) “Plasma myostatin measured by a competitive ELISA using a highly specific antiserum”, Clin Chim Acta., 413(15-16):1288-1294. cited by applicant
      Wolfman et al., (2003) “Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases”, Proc Natl Acad Sci U.S.A., 100(26):15842-15846. cited by applicant
      Zhao et al., (2016) “Pharmacokinetics, pharmacodynamics, and efficacy of a small molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy”, Human Molecular Genetics, 25(10):1885-1899. cited by applicant
      Amthor et al. “Lack of myostatin results in excessive muscle growth but impaired force generation,” Proc Natl Acad Sci U S A. Feb. 6, 2007;104(6):1835-40. cited by applicant
      Benjamini et al. (1991) Immunology: A Short Course, 2nd edition, p. 40 only. cited by applicant
      Castellana et al. “Resurrection of a clinical antibody: template proteogenomic de novo proteomic sequencing and reverse engineering of an anti-lymphotoxin-α antibody”, Proteomics. Feb. 2011;11(3):395-405. cited by applicant
      Deguise et al. (2017) “New insights into SMA pathogenesis: immune dysfunction and neuroinflammation,” Ann Clin Transl Neurol. 4(7):522-53. cited by applicant
      Extended European Search Report in EP23158609.0, dated Aug. 8, 2023, 27 pages. cited by applicant
      Jablonka et al. (2022) “Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders,” Neurol Res Pract. 4(7):522-530. cited by applicant
      Rindt et al. (2012) “Transgenic inactivation of murine myostatin does not decrease the severity of disease in a model of Spinal Muscular Atrophy,” Neuromuscul Disord. 22(3):277-85. cited by applicant
      Suh et al. (2020) “GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone,” Proc Natl Acad Sci U S A. 3;117(9):4910-4920. cited by applicant
    • Primary Examiner:
      Howard, Zachary C
    • Attorney, Agent or Firm:
      Finnegan, Henderson, Farabow, Garrett, & Dunner, LLP
    • Accession Number:
      edspgr.11925683