AU2003216345A1 - Follistatin domain containing proteins - Google Patents
Follistatin domain containing proteins Download PDFInfo
- Publication number
- AU2003216345A1 AU2003216345A1 AU2003216345A AU2003216345A AU2003216345A1 AU 2003216345 A1 AU2003216345 A1 AU 2003216345A1 AU 2003216345 A AU2003216345 A AU 2003216345A AU 2003216345 A AU2003216345 A AU 2003216345A AU 2003216345 A1 AU2003216345 A1 AU 2003216345A1
- Authority
- AU
- Australia
- Prior art keywords
- protein
- gdf
- follistatin
- proteins
- disorder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 108090000623 proteins and genes Proteins 0.000 title claims description 323
- 102000004169 proteins and genes Human genes 0.000 title claims description 306
- 108010014612 Follistatin Proteins 0.000 title claims description 139
- 102000016970 Follistatin Human genes 0.000 title description 123
- 238000000034 method Methods 0.000 claims description 69
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 67
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 208000035475 disorder Diseases 0.000 claims description 38
- 230000004048 modification Effects 0.000 claims description 33
- 238000012986 modification Methods 0.000 claims description 33
- 210000003205 muscle Anatomy 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 29
- 101001021404 Homo sapiens G-protein coupled receptor-associated sorting protein 2 Proteins 0.000 claims description 18
- 102100020722 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 Human genes 0.000 claims description 14
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 230000013595 glycosylation Effects 0.000 claims description 12
- 238000006206 glycosylation reaction Methods 0.000 claims description 12
- 230000000087 stabilizing effect Effects 0.000 claims description 12
- 108010088751 Albumins Proteins 0.000 claims description 11
- 102000009027 Albumins Human genes 0.000 claims description 11
- 208000021642 Muscular disease Diseases 0.000 claims description 10
- 239000000872 buffer Substances 0.000 claims description 10
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 206010028289 Muscle atrophy Diseases 0.000 claims description 9
- -1 agrins Proteins 0.000 claims description 9
- 208000030159 metabolic disease Diseases 0.000 claims description 9
- 201000000585 muscular atrophy Diseases 0.000 claims description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- 102100029379 Follistatin-related protein 3 Human genes 0.000 claims description 8
- 208000008589 Obesity Diseases 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 8
- 230000008901 benefit Effects 0.000 claims description 7
- 201000006938 muscular dystrophy Diseases 0.000 claims description 7
- 230000003442 weekly effect Effects 0.000 claims description 7
- 101000840577 Homo sapiens Insulin-like growth factor-binding protein 7 Proteins 0.000 claims description 6
- 101000588007 Homo sapiens SPARC-like protein 1 Proteins 0.000 claims description 6
- 102100029228 Insulin-like growth factor-binding protein 7 Human genes 0.000 claims description 6
- 108010056852 Myostatin Proteins 0.000 claims description 6
- 208000010316 Myotonia congenita Diseases 0.000 claims description 6
- 108010077077 Osteonectin Proteins 0.000 claims description 6
- 102100037599 SPARC Human genes 0.000 claims description 6
- 102100031581 SPARC-like protein 1 Human genes 0.000 claims description 6
- 210000000988 bone and bone Anatomy 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 210000000577 adipose tissue Anatomy 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 230000020763 muscle atrophy Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 208000026062 Tissue disease Diseases 0.000 claims description 4
- 201000001421 hyperglycemia Diseases 0.000 claims description 4
- 230000006320 pegylation Effects 0.000 claims description 4
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 208000035810 Denervation atrophy Diseases 0.000 claims description 3
- 238000009007 Diagnostic Kit Methods 0.000 claims description 3
- 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 claims description 3
- 208000001441 Familial Periodic Paralyses Diseases 0.000 claims description 3
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 claims description 3
- 206010028372 Muscular weakness Diseases 0.000 claims description 3
- 206010028424 Myasthenic syndrome Diseases 0.000 claims description 3
- 206010028629 Myoglobinuria Diseases 0.000 claims description 3
- 206010052181 Oculopharyngeal dystrophy Diseases 0.000 claims description 3
- 201000009110 Oculopharyngeal muscular dystrophy Diseases 0.000 claims description 3
- 230000009693 chronic damage Effects 0.000 claims description 3
- 201000011474 congenital myopathy Diseases 0.000 claims description 3
- 201000009338 distal myopathy Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 claims description 3
- 206010016208 familial periodic paralysis Diseases 0.000 claims description 3
- 230000004927 fusion Effects 0.000 claims description 3
- 230000036473 myasthenia Effects 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 206010030875 ophthalmoplegia Diseases 0.000 claims description 3
- 230000001314 paroxysmal effect Effects 0.000 claims description 3
- 230000000750 progressive effect Effects 0.000 claims description 3
- 208000001076 sarcopenia Diseases 0.000 claims description 3
- 230000008736 traumatic injury Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 102100020921 Follistatin Human genes 0.000 claims 16
- 108010012820 Follistatin-Related Proteins Proteins 0.000 claims 4
- 102000004472 Myostatin Human genes 0.000 claims 4
- 125000000837 carbohydrate group Chemical group 0.000 claims 2
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 claims 1
- 201000006815 congenital muscular dystrophy Diseases 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 267
- 210000004027 cell Anatomy 0.000 description 45
- 230000000694 effects Effects 0.000 description 41
- 102000004196 processed proteins & peptides Human genes 0.000 description 35
- 210000002966 serum Anatomy 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 34
- 150000001413 amino acids Chemical class 0.000 description 34
- 125000003275 alpha amino acid group Chemical group 0.000 description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 239000002773 nucleotide Substances 0.000 description 25
- 125000003729 nucleotide group Chemical group 0.000 description 25
- 239000011324 bead Substances 0.000 description 24
- 239000012634 fragment Substances 0.000 description 24
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 24
- 239000000499 gel Substances 0.000 description 21
- 101100264016 Mus musculus Wfikkn2 gene Proteins 0.000 description 19
- 230000027455 binding Effects 0.000 description 19
- 239000013598 vector Substances 0.000 description 19
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 description 17
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- 230000000875 corresponding effect Effects 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 15
- 238000004885 tandem mass spectrometry Methods 0.000 description 15
- 230000001225 therapeutic effect Effects 0.000 description 15
- 238000001262 western blot Methods 0.000 description 15
- 239000003636 conditioned culture medium Substances 0.000 description 14
- 150000002500 ions Chemical class 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 13
- 102000004877 Insulin Human genes 0.000 description 12
- 108090001061 Insulin Proteins 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 235000018417 cysteine Nutrition 0.000 description 12
- 239000003102 growth factor Substances 0.000 description 12
- 229940125396 insulin Drugs 0.000 description 12
- 101100264015 Homo sapiens WFIKKN2 gene Proteins 0.000 description 11
- 230000004071 biological effect Effects 0.000 description 11
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 210000002027 skeletal muscle Anatomy 0.000 description 11
- 108010059616 Activins Proteins 0.000 description 10
- 102000005606 Activins Human genes 0.000 description 10
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 10
- 239000000488 activin Substances 0.000 description 10
- 150000001720 carbohydrates Chemical group 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 239000012133 immunoprecipitate Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 229910052709 silver Inorganic materials 0.000 description 10
- 239000004332 silver Substances 0.000 description 10
- 239000012521 purified sample Substances 0.000 description 9
- 230000001177 retroviral effect Effects 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 108060001084 Luciferase Proteins 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000004949 mass spectrometry Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000003381 stabilizer Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- 239000004473 Threonine Substances 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- 229920000936 Agarose Polymers 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 208000029578 Muscle disease Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 6
- 102000004142 Trypsin Human genes 0.000 description 6
- 108090000631 Trypsin Proteins 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 210000001789 adipocyte Anatomy 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 230000004190 glucose uptake Effects 0.000 description 6
- 239000000710 homodimer Substances 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 239000012588 trypsin Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000869690 Homo sapiens Protein S100-A8 Proteins 0.000 description 5
- 102100032442 Protein S100-A8 Human genes 0.000 description 5
- 229940122055 Serine protease inhibitor Drugs 0.000 description 5
- 101710102218 Serine protease inhibitor Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 238000001261 affinity purification Methods 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 102000047114 human GPRASP2 Human genes 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000003001 serine protease inhibitor Substances 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 101001062529 Homo sapiens Follistatin-related protein 3 Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 101100373101 Mus musculus Wfikkn1 gene Proteins 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229940009098 aspartate Drugs 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 101150004578 gdf-8 gene Proteins 0.000 description 4
- 230000014101 glucose homeostasis Effects 0.000 description 4
- 229930195712 glutamate Natural products 0.000 description 4
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 238000001114 immunoprecipitation Methods 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 101100348617 Candida albicans (strain SC5314 / ATCC MYA-2876) NIK1 gene Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102000004420 Creatine Kinase Human genes 0.000 description 3
- 108010042126 Creatine kinase Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 3
- 101000886562 Homo sapiens Growth/differentiation factor 8 Proteins 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 230000004988 N-glycosylation Effects 0.000 description 3
- 102000000001 Netrin domains Human genes 0.000 description 3
- 108050008395 Netrin domains Proteins 0.000 description 3
- 230000004989 O-glycosylation Effects 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 101100007329 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS1 gene Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 101710087237 Whey acidic protein Proteins 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000001246 colloidal dispersion Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 230000001002 morphogenetic effect Effects 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 210000003098 myoblast Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 210000000229 preadipocyte Anatomy 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000003656 tris buffered saline Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 102000001690 Factor VIII Human genes 0.000 description 2
- 108010054218 Factor VIII Proteins 0.000 description 2
- 208000036119 Frailty Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 241000713858 Harvey murine sarcoma virus Species 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 102400000401 Latency-associated peptide Human genes 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- 208000029725 Metabolic bone disease Diseases 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 101001075141 Mus musculus Growth/differentiation factor 8 Proteins 0.000 description 2
- 208000011623 Obstructive Lung disease Diseases 0.000 description 2
- 206010049088 Osteopenia Diseases 0.000 description 2
- 241001504519 Papio ursinus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000037429 base substitution Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000022811 deglycosylation Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 201000003617 glucocorticoid-induced osteoporosis Diseases 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000002710 gonadal effect Effects 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 235000018343 nutrient deficiency Nutrition 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- KYBXNPIASYUWLN-WUCPZUCCSA-N (2s)-5-hydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CC[C@@H](C(O)=O)N1 KYBXNPIASYUWLN-WUCPZUCCSA-N 0.000 description 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- 102100031928 40S ribosomal protein S29 Human genes 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- 101150079978 AGRN gene Proteins 0.000 description 1
- 208000011732 Abnormal glucose homeostasis Diseases 0.000 description 1
- 102100040026 Agrin Human genes 0.000 description 1
- 108700019743 Agrin Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 241000714235 Avian retrovirus Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101000984722 Bos taurus Pancreatic trypsin inhibitor Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 101000942967 Homo sapiens Leukemia inhibitory factor Proteins 0.000 description 1
- 101000855019 Homo sapiens WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102100026019 Interleukin-6 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 101800001155 Latency-associated peptide Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100281691 Mus musculus Fstl3 gene Proteins 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100026918 Phospholipase A2 Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 102100026159 Tomoregulin-1 Human genes 0.000 description 1
- 101710175559 Tomoregulin-1 Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 108010023082 activin A Proteins 0.000 description 1
- 238000003450 affinity purification method Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 239000001055 blue pigment Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 210000004900 c-terminal fragment Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 229930183167 cerebroside Natural products 0.000 description 1
- 150000001784 cerebrosides Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000002468 fat body Anatomy 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 108091005995 glycated hemoglobin Proteins 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 102000028718 growth factor binding proteins Human genes 0.000 description 1
- 108091009353 growth factor binding proteins Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 230000002621 immunoprecipitating effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000009753 muscle formation Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 230000007672 negative regulation of muscle organ development Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108010093173 ribosomal protein S29 Proteins 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/06—Anabolic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4743—Insulin-like growth factor binding protein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Child & Adolescent Psychology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35784602P | 2002-02-21 | 2002-02-21 | |
| US60/357,846 | 2002-02-21 | ||
| US43464502P | 2002-12-20 | 2002-12-20 | |
| US60/434,645 | 2002-12-20 | ||
| PCT/US2003/005150 WO2003072714A2 (en) | 2002-02-21 | 2003-02-21 | Follistatin domain containing proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2003216345A1 true AU2003216345A1 (en) | 2003-09-09 |
Family
ID=27767537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003216345A Withdrawn AU2003216345A1 (en) | 2002-02-21 | 2003-02-21 | Follistatin domain containing proteins |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US7572763B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1572934A4 (cg-RX-API-DMAC7.html) |
| JP (2) | JP4429728B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR20040096592A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2003216345A1 (cg-RX-API-DMAC7.html) |
| BR (1) | BR0307871A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2476654A1 (cg-RX-API-DMAC7.html) |
| MX (1) | MXPA04008149A (cg-RX-API-DMAC7.html) |
| NO (1) | NO20043564L (cg-RX-API-DMAC7.html) |
| PL (1) | PL374966A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2003072714A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200526779A (en) * | 2001-02-08 | 2005-08-16 | Wyeth Corp | Modified and stabilized GDF propeptides and uses thereof |
| US7320789B2 (en) * | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| JP4429729B2 (ja) * | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | Ｇａｓｐ１；フォリスタチンドメイン含有タンパク質 |
| JP4429728B2 (ja) | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | フォリスタチン（ｆｏｌｌｉｓｔａｔｉｎ）ドメイン含有タンパク質 |
| US7193069B2 (en) | 2002-03-22 | 2007-03-20 | Research Association For Biotechnology | Full-length cDNA |
| DE60331778D1 (de) * | 2002-09-16 | 2010-04-29 | Univ Johns Hopkins | Metalloproteaseaktivierung von myostatin und verfahren zur modulation der myostatinaktivität |
| AR047392A1 (es) | 2002-10-22 | 2006-01-18 | Wyeth Corp | Neutralizacion de anticuerpos contra gdf 8 y su uso para tales fines |
| US20040223966A1 (en) * | 2002-10-25 | 2004-11-11 | Wolfman Neil M. | ActRIIB fusion polypeptides and uses therefor |
| JP5568208B2 (ja) * | 2003-01-14 | 2014-08-06 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | 癌治療感作物質 |
| JP5110877B2 (ja) * | 2003-06-02 | 2012-12-26 | ワイス・エルエルシー | 神経筋障害を処置するための、コルチコステロイドと組み合わせたミオスタチン（ｇｄｆ８）インヒビターの使用 |
| EP2289908B1 (en) * | 2003-07-11 | 2013-08-07 | Evotec International GmbH | Use of DG177 secreted protein products for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome |
| AU2005219441A1 (en) | 2004-03-02 | 2005-09-15 | Acceleron Pharma Inc. | ALK7 and myostatin inhibitors and uses thereof |
| US8420603B2 (en) * | 2004-05-14 | 2013-04-16 | Abraxis Bioscience, Llc | SPARC and methods of use thereof |
| AU2006249235B2 (en) | 2004-05-14 | 2010-11-11 | Abraxis Bioscience, Llc | Sparc and methods of use thereof |
| US9045553B2 (en) | 2004-05-27 | 2015-06-02 | Acceleron Pharma, Inc. | Cerberus/Coco derivatives and uses thereof |
| JP2008500373A (ja) * | 2004-05-27 | 2008-01-10 | アクセルロン ファーマ インコーポレーテッド | ケルベロス（Ｃｅｒｂｅｒｕｓ）／ココ（Ｃｏｃｏ）誘導体およびそれらの使用 |
| EP1778275A2 (en) * | 2004-08-12 | 2007-05-02 | Wyeth | Combination therapy for diabetes, obesity, and cardiovascular diseases using gdf-8 inhibitors |
| TWI364458B (en) | 2004-08-27 | 2012-05-21 | Wyeth Res Ireland Ltd | Production of tnfr-lg |
| US7294484B2 (en) | 2004-08-27 | 2007-11-13 | Wyeth Research Ireland Limited | Production of polypeptides |
| US7335491B2 (en) | 2004-08-27 | 2008-02-26 | Wyeth Research Ireland Limited | Production of anti-abeta |
| NZ538097A (en) * | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| MX2007011405A (es) * | 2005-03-23 | 2007-10-11 | Wyeth Corp | Deteccion de una respuesta inmune para agentes moduladores de crecimiento y la diferenciacion del factor 8 (gdf 8). |
| CN101147068A (zh) * | 2005-03-23 | 2008-03-19 | 惠氏公司 | Gdf-8调节剂的检测 |
| AU2006283725B2 (en) | 2005-08-19 | 2012-02-16 | The Trustees Of The University Of Pennsylvania | Antagonist antibodies against GDF-8 and uses in treatment of ALS and other GDF-8-associated disorders |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| JP2009531459A (ja) * | 2006-03-28 | 2009-09-03 | ワイス | 骨障害の治療のためのｇｄｆ−９／ｂｍｐ−１５モジュレータ |
| JP2010512326A (ja) | 2006-12-08 | 2010-04-22 | アクセルロン ファーマ， インコーポレイテッド | Ｃｅｒｂｅｒｕｓ、Ｃｏｃｏおよびこれらの誘導体の使用 |
| US8895016B2 (en) * | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| TWI782836B (zh) | 2007-02-02 | 2022-11-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ActRIIB的變體與其用途 |
| PE20091163A1 (es) | 2007-11-01 | 2009-08-09 | Wyeth Corp | Anticuerpos para gdf8 |
| US20100015144A1 (en) | 2008-06-26 | 2010-01-21 | Acceleron Pharma Inc. | Methods for dosing an activin-actriia antagonist and monitoring of treated patients |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| EP2606119A1 (en) | 2010-08-20 | 2013-06-26 | Wyeth LLC | Cell culture of growth factor-free adapted cells |
| KR20140077977A (ko) | 2011-10-21 | 2014-06-24 | 화이자 인코포레이티드 | 철을 첨가하여 세포 배양을 개선하는 방법 |
| US20180193306A1 (en) | 2012-03-23 | 2018-07-12 | Cardero Therapeutics, Inc. | Compounds and compositions for the treatment of muscular disorders and bone disorders |
| EP2861617A1 (en) | 2012-06-15 | 2015-04-22 | Pfizer Inc. | Improved antagonist antibodies against gdf-8 and uses therefor |
| AU2013313282B2 (en) | 2012-08-01 | 2018-02-01 | Ikaika Therapeutics, Llc | Mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (LTBP4) |
| WO2014066486A2 (en) * | 2012-10-24 | 2014-05-01 | Celgene Corporation | Biomarker for use in treating anemia |
| US20150266950A1 (en) | 2012-10-24 | 2015-09-24 | Celgene Corporation | Methods for treating anemia |
| AU2013337677B2 (en) | 2012-11-02 | 2018-06-28 | Celgene Corporation | Activin-ActRII antagonists and uses for treating bone and other disorders |
| EA201590719A1 (ru) | 2013-01-25 | 2015-12-30 | Шир Хьюман Дженетик Терапис, Инк. | Фоллистатин в лечении мышечной дистрофии дюшенна |
| JP2014151438A (ja) * | 2013-02-04 | 2014-08-25 | Koito Mfg Co Ltd | レーザー溶着方法 |
| GB201308117D0 (en) * | 2013-05-06 | 2013-06-12 | Univ Leuven Kath | Inhibitor of calcifying disorders |
| US10010498B2 (en) | 2014-06-04 | 2018-07-03 | Acceleron Pharma Inc. | Methods for treatment of amyotrophic lateral sclerosis with follistatin fusion proteins |
| JP6568110B2 (ja) | 2014-06-04 | 2019-08-28 | アクセルロン ファーマ， インコーポレイテッド | フォリスタチンポリペプチドによる障害の処置のための方法および組成物 |
| JP2018510637A (ja) | 2015-03-26 | 2018-04-19 | アクセルロン ファーマ， インコーポレイテッド | フォリスタチン関連融合タンパク質およびその使用 |
| EA201990226A1 (ru) | 2016-07-27 | 2019-08-30 | Акселерон Фарма Инк. | Способы и композиции для лечения миелофиброза |
| WO2018218273A1 (en) * | 2017-05-29 | 2018-12-06 | Paranta Biosciences Limited | Method of treating hypertension and kidney disease |
| KR101822633B1 (ko) * | 2017-08-22 | 2018-01-26 | (주)진셀팜 | 폴리스타틴 유래 생리활성 펩타이드, 및 이의 용도 |
| BR112020016923A2 (pt) * | 2018-02-20 | 2020-12-15 | Epirium Bio Inc. | Método para reverter ou atenuar lesão, ou fraqueza ou perda óssea, ou para evitar fraturas em um indivíduo, e, composição |
| KR20210117271A (ko) | 2018-12-21 | 2021-09-28 | 노쓰웨스턴유니버시티 | 근막 손상 예방 및 치료를 위한 아넥신의 사용근각 손상 예방 및 치료를 위한 아넥신의 사용 |
| US20220062299A1 (en) | 2018-12-26 | 2022-03-03 | Northwestern University | Use of glucocorticoid steroids in preventing and treating conditions of muscle wasting, aging and metabolic disorder |
| MX2019015589A (es) * | 2019-12-19 | 2021-06-21 | Centro De Investig Y Asistencia En Tecnologia Y Diseno Del Estado De Jalisco A C | Molécula sintética de adn con potenciador autorregulado por hipoxia y/o inflamación para uso como agente terapéutico de enfermedades inflamatorias y degeneración tisular. |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| JPS5896026A (ja) | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| EP0098110B1 (en) | 1982-06-24 | 1989-10-18 | NIHON CHEMICAL RESEARCH KABUSHIKI KAISHA also known as JAPAN CHEMICAL RESEARCH CO., LTD | Long-acting composition |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US5116944A (en) | 1989-12-29 | 1992-05-26 | Neorx Corporation | Conjugates having improved characteristics for in vivo administration |
| US6162896A (en) * | 1991-05-10 | 2000-12-19 | The Salk Institute For Biological Studies | Recombinant vertebrate activin receptors |
| DK0590058T3 (da) * | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
| US20030074680A1 (en) * | 1993-03-19 | 2003-04-17 | Johns Hopkins University School Of Medicine | Growth differentiation factor-8 |
| ES2201076T3 (es) * | 1993-03-19 | 2004-03-16 | The Johns Hopkins University School Of Medicine | Factor-8 de diferenciacion del crecimiento. |
| US5994618A (en) * | 1997-02-05 | 1999-11-30 | Johns Hopkins University School Of Medicine | Growth differentiation factor-8 transgenic mice |
| US6673534B1 (en) * | 1995-10-26 | 2004-01-06 | The Johns Hopkins University School Of Medicine | Methods for detection of mutations in myostatin variants |
| US6465239B1 (en) * | 1993-03-19 | 2002-10-15 | The John Hopkins University School Of Medicine | Growth differentiation factor-8 nucleic acid and polypeptides from aquatic species and non-human transgenic aquatic species |
| US7393682B1 (en) | 1993-03-19 | 2008-07-01 | The Johns Hopkins University School Of Medicine | Polynucleotides encoding promyostatin polypeptides |
| US6607884B1 (en) * | 1993-03-19 | 2003-08-19 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-8 |
| ES2213745T3 (es) * | 1993-05-12 | 2004-09-01 | Genetics Institute, Llc | Composiciones de bmp-11. |
| DE69434739T2 (de) * | 1993-08-26 | 2007-05-10 | Genetics Institute, LLC, Cambridge | Menschliche Knochen-morphogenetische Proteine zur Verwendung bei neuronaler Rehgeneration |
| US7332575B2 (en) * | 1994-03-18 | 2008-02-19 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-8 nucleic acid and polypeptide from aquatic species, and transgenic aquatic species |
| ATE305036T1 (de) | 1994-07-08 | 2005-10-15 | Univ Johns Hopkins Med | Wachstums-differenzierungsfaktor-11 |
| US6008434A (en) | 1994-07-08 | 1999-12-28 | Johns Hopkins University School Of Medicine | Growth differentiation factor-11 transgenic mice |
| US5723125A (en) * | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
| AU6274298A (en) | 1997-02-05 | 1998-08-25 | Johns Hopkins University School Of Medicine, The | Growth differentiation factor-8 |
| US6548644B1 (en) * | 1997-03-10 | 2003-04-15 | Immunex Corporation | Site protected protein modification |
| US6696260B1 (en) | 1997-08-01 | 2004-02-24 | The Johns Hopkins University School Of Medicine | Methods to identify growth differentiation factor (GDF) binding proteins |
| US6891082B2 (en) * | 1997-08-01 | 2005-05-10 | The Johns Hopkins University School Of Medicine | Transgenic non-human animals expressing a truncated activintype II receptor |
| US6656475B1 (en) * | 1997-08-01 | 2003-12-02 | The Johns Hopkins University School Of Medicine | Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same |
| AU8921698A (en) * | 1997-08-29 | 1999-03-16 | Human Genome Sciences, Inc. | Follistatin-3 |
| WO1999024057A2 (en) | 1997-11-07 | 1999-05-20 | Genetics Inst | Neuronal uses of bmp-11 |
| US5942420A (en) * | 1997-11-17 | 1999-08-24 | Millennium Biotherapeutics, Inc. | Molecules of the follistatin-related protein family and uses therefor |
| US6369201B1 (en) * | 1998-02-19 | 2002-04-09 | Metamorphix International, Inc. | Myostatin multimers |
| US6004937A (en) | 1998-03-09 | 1999-12-21 | Genetics Institute, Inc. | Use of follistatin to modulate growth and differentiation factor 8 [GDF-8] and bone morphogenic protein 11 [BMP-11] |
| US6368597B1 (en) * | 1998-05-06 | 2002-04-09 | Matamorphix, Inc. | Methods of treating diabetes |
| EP1105477A1 (en) | 1998-08-20 | 2001-06-13 | Regeneron Pharmaceuticals, Inc. | Dcr5, a bmp-binding protein, and applications thereof |
| JP2002527065A (ja) * | 1998-10-15 | 2002-08-27 | ザイモジェネティクス，インコーポレイティド | フォリスタチン関連タンパク質ｚｆｓｔａ２ |
| DE60027135T2 (de) | 1999-01-21 | 2007-01-11 | Metamorphix, Inc. | Inhibitoren für wachstumdifferenzierungsfaktor und ihre anwendungen |
| AU6098300A (en) | 1999-07-16 | 2001-02-05 | Human Genome Sciences, Inc. | Follistatin-3 |
| US7098372B1 (en) * | 1999-09-13 | 2006-08-29 | Wyeth | Pharmaceutical compositions and methods of using secreted frizzled related protein |
| WO2001032871A2 (en) * | 1999-11-03 | 2001-05-10 | Zymogenetics, Inc. | Follistatin-related protein zfsta4 |
| AU2001241817A1 (en) | 2000-02-29 | 2001-09-12 | Zymogenetics Inc. | Kunitz domain polypeptide zkun8 |
| CA2401552A1 (en) * | 2000-03-03 | 2001-09-15 | Curagen Corporation | Proteins named fctrx and nucleic acids encoding same |
| EP1983055A1 (en) * | 2000-04-12 | 2008-10-22 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7037501B2 (en) * | 2001-01-04 | 2006-05-02 | Regents Of The University Of Minnesota | Myostatin immnoconjugate |
| TW200526779A (en) | 2001-02-08 | 2005-08-16 | Wyeth Corp | Modified and stabilized GDF propeptides and uses thereof |
| US7320789B2 (en) | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| JP4429729B2 (ja) * | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | Ｇａｓｐ１；フォリスタチンドメイン含有タンパク質 |
| JP4429728B2 (ja) | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | フォリスタチン（ｆｏｌｌｉｓｔａｔｉｎ）ドメイン含有タンパク質 |
| DE60331778D1 (de) * | 2002-09-16 | 2010-04-29 | Univ Johns Hopkins | Metalloproteaseaktivierung von myostatin und verfahren zur modulation der myostatinaktivität |
| AR047392A1 (es) * | 2002-10-22 | 2006-01-18 | Wyeth Corp | Neutralizacion de anticuerpos contra gdf 8 y su uso para tales fines |
| US20040223966A1 (en) | 2002-10-25 | 2004-11-11 | Wolfman Neil M. | ActRIIB fusion polypeptides and uses therefor |
| EA009056B1 (ru) | 2002-12-20 | 2007-10-26 | Амген, Инк. | Связывающие агенты, ингибирующие миостатин |
| CN101147068A (zh) * | 2005-03-23 | 2008-03-19 | 惠氏公司 | Gdf-8调节剂的检测 |
| MX2007011405A (es) * | 2005-03-23 | 2007-10-11 | Wyeth Corp | Deteccion de una respuesta inmune para agentes moduladores de crecimiento y la diferenciacion del factor 8 (gdf 8). |
-
2003
- 2003-02-21 JP JP2003571402A patent/JP4429728B2/ja not_active Expired - Fee Related
- 2003-02-21 AU AU2003216345A patent/AU2003216345A1/en not_active Withdrawn
- 2003-02-21 EP EP03743174A patent/EP1572934A4/en not_active Withdrawn
- 2003-02-21 PL PL03374966A patent/PL374966A1/xx not_active Application Discontinuation
- 2003-02-21 US US10/369,738 patent/US7572763B2/en not_active Expired - Fee Related
- 2003-02-21 BR BR0307871-0A patent/BR0307871A/pt not_active IP Right Cessation
- 2003-02-21 CA CA002476654A patent/CA2476654A1/en not_active Abandoned
- 2003-02-21 WO PCT/US2003/005150 patent/WO2003072714A2/en not_active Ceased
- 2003-02-21 MX MXPA04008149A patent/MXPA04008149A/es active IP Right Grant
- 2003-02-21 KR KR10-2004-7012978A patent/KR20040096592A/ko not_active Withdrawn
-
2004
- 2004-08-26 NO NO20043564A patent/NO20043564L/no not_active Application Discontinuation
-
2009
- 2009-06-02 US US12/476,489 patent/US20100047259A1/en not_active Abandoned
- 2009-09-14 JP JP2009212564A patent/JP2009286804A/ja active Pending
-
2010
- 2010-09-17 US US12/884,371 patent/US20110020372A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20100047259A1 (en) | 2010-02-25 |
| EP1572934A4 (en) | 2007-12-19 |
| MXPA04008149A (es) | 2005-06-17 |
| NO20043564L (no) | 2004-11-03 |
| JP2005531505A (ja) | 2005-10-20 |
| US7572763B2 (en) | 2009-08-11 |
| CA2476654A1 (en) | 2003-09-04 |
| KR20040096592A (ko) | 2004-11-16 |
| WO2003072714A2 (en) | 2003-09-04 |
| PL374966A1 (en) | 2005-11-14 |
| EP1572934A2 (en) | 2005-09-14 |
| JP4429728B2 (ja) | 2010-03-10 |
| BR0307871A (pt) | 2005-04-12 |
| JP2009286804A (ja) | 2009-12-10 |
| US20110020372A1 (en) | 2011-01-27 |
| US20030180306A1 (en) | 2003-09-25 |
| WO2003072714A3 (en) | 2006-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7956038B2 (en) | GASP1: a follistatin domain containing protein | |
| US7572763B2 (en) | Follistatin domain containing proteins | |
| EP1397492B1 (en) | Modified and stabilized gdf propeptides and uses thereof | |
| AU2002243852A1 (en) | Modified and stabilized GDF propeptides and uses thereof | |
| ZA200406542B (en) | Gasp 1 : A follistatin domain containing protein | |
| EP1790726B1 (en) | Modified and stabilized GDF propeptides and uses thereof | |
| HK1062457B (en) | Modified and stabilized gdf propeptides and uses thereof | |
| HK1104578A (en) | Modified and stabilized gdf propeptides and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK12 | Application lapsed section 141(1)/reg 8.3(2) - applicant filed a written notice of withdrawal |