EA020510B1 - Модифицированные полипептиды рецептора активина и их применение - Google Patents
Модифицированные полипептиды рецептора активина и их применение Download PDFInfo
- Publication number
- EA020510B1 EA020510B1 EA200970810A EA200970810A EA020510B1 EA 020510 B1 EA020510 B1 EA 020510B1 EA 200970810 A EA200970810 A EA 200970810A EA 200970810 A EA200970810 A EA 200970810A EA 020510 B1 EA020510 B1 EA 020510B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino acid
- polypeptide
- sequence
- substituent
- replacement
- Prior art date
Links
- 102000018918 Activin Receptors Human genes 0.000 title claims description 11
- 108010052946 Activin Receptors Proteins 0.000 title claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 313
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 306
- 229920001184 polypeptide Polymers 0.000 claims abstract description 303
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 117
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 112
- 238000000034 method Methods 0.000 claims abstract description 71
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 69
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 69
- 239000002157 polynucleotide Substances 0.000 claims abstract description 69
- 108010056852 Myostatin Proteins 0.000 claims abstract description 67
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 claims abstract description 66
- 239000000203 mixture Substances 0.000 claims abstract description 51
- 230000000694 effects Effects 0.000 claims abstract description 49
- 108010023082 activin A Proteins 0.000 claims abstract description 41
- 108010059616 Activins Proteins 0.000 claims abstract description 30
- 239000000488 activin Substances 0.000 claims abstract description 29
- 230000027455 binding Effects 0.000 claims abstract description 28
- 239000013598 vector Substances 0.000 claims abstract description 25
- 206010028289 Muscle atrophy Diseases 0.000 claims abstract description 20
- 201000000585 muscular atrophy Diseases 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
- 150000001413 amino acids Chemical class 0.000 claims description 128
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 229910052700 potassium Inorganic materials 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 230000014509 gene expression Effects 0.000 claims description 36
- 210000003205 muscle Anatomy 0.000 claims description 33
- 102000005606 Activins Human genes 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052698 phosphorus Inorganic materials 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 238000006467 substitution reaction Methods 0.000 claims description 20
- 230000020763 muscle atrophy Effects 0.000 claims description 19
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 206010006895 Cachexia Diseases 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 102000005962 receptors Human genes 0.000 claims description 14
- 108020003175 receptors Proteins 0.000 claims description 14
- 230000000295 complement effect Effects 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 230000012010 growth Effects 0.000 claims description 8
- 206010003694 Atrophy Diseases 0.000 claims description 7
- 230000037444 atrophy Effects 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 7
- 206010002261 Androgen deficiency Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 208000030159 metabolic disease Diseases 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 5
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
- 230000004069 differentiation Effects 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 230000005486 microgravity Effects 0.000 claims description 4
- 230000002035 prolonged effect Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000010392 Bone Fractures Diseases 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 208000037157 Azotemia Diseases 0.000 claims description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 208000011623 Obstructive Lung disease Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 230000032683 aging Effects 0.000 claims description 2
- 208000003295 carpal tunnel syndrome Diseases 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 208000001076 sarcopenia Diseases 0.000 claims description 2
- 208000009852 uremia Diseases 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 51
- 230000006735 deficit Effects 0.000 claims 1
- 208000016253 exhaustion Diseases 0.000 claims 1
- 230000002503 metabolic effect Effects 0.000 claims 1
- 238000003259 recombinant expression Methods 0.000 claims 1
- 208000037765 diseases and disorders Diseases 0.000 abstract description 3
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 abstract 1
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 abstract 1
- 102100026818 Inhibin beta E chain Human genes 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 103
- 241000272814 Anser sp. Species 0.000 description 84
- 235000018102 proteins Nutrition 0.000 description 78
- 101100460719 Mus musculus Noto gene Proteins 0.000 description 74
- 101100187345 Xenopus laevis noto gene Proteins 0.000 description 74
- 235000001014 amino acid Nutrition 0.000 description 73
- 229940024606 amino acid Drugs 0.000 description 69
- 210000004027 cell Anatomy 0.000 description 63
- 239000011093 chipboard Substances 0.000 description 61
- 244000144619 Abrus precatorius Species 0.000 description 38
- 230000001052 transient effect Effects 0.000 description 37
- 238000011282 treatment Methods 0.000 description 26
- 102220099807 rs201794121 Human genes 0.000 description 25
- 239000002957 persistent organic pollutant Substances 0.000 description 24
- 230000002776 aggregation Effects 0.000 description 22
- 238000004220 aggregation Methods 0.000 description 22
- 238000002474 experimental method Methods 0.000 description 22
- 238000000746 purification Methods 0.000 description 20
- 108010076504 Protein Sorting Signals Proteins 0.000 description 18
- 230000037396 body weight Effects 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 102220604157 Adenosine deaminase_K64A_mutation Human genes 0.000 description 16
- 239000003925 fat Substances 0.000 description 16
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- DSGIVWSDDRDJIO-ZXXMMSQZSA-N Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DSGIVWSDDRDJIO-ZXXMMSQZSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 235000013305 food Nutrition 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000011813 knockout mouse model Methods 0.000 description 13
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 12
- 239000000463 material Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 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 8
- 101100203200 Danio rerio shha gene Proteins 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 238000002513 implantation Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 210000001672 ovary Anatomy 0.000 description 8
- 239000000600 sorbitol Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 210000003141 lower extremity Anatomy 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 102220511767 Calreticulin_K40A_mutation Human genes 0.000 description 6
- 238000011887 Necropsy Methods 0.000 description 6
- 244000284012 Vetiveria zizanioides Species 0.000 description 6
- 235000007769 Vetiveria zizanioides Nutrition 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000007914 intraventricular administration Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 210000001550 testis Anatomy 0.000 description 6
- 241000272525 Anas platyrhynchos Species 0.000 description 5
- 201000006935 Becker muscular dystrophy Diseases 0.000 description 5
- 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 5
- 108060003951 Immunoglobulin Proteins 0.000 description 5
- 239000003636 conditioned culture medium Substances 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 235000012631 food intake Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 102000018358 immunoglobulin Human genes 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000004471 Glycine Substances 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 208000016261 weight loss Diseases 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical class [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 238000000149 argon plasma sintering Methods 0.000 description 3
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000644 propagated effect Effects 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 2
- 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 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- -1 aspargin Chemical compound 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 108010067471 inhibin A Proteins 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002534 molecular mass spectrometry Methods 0.000 description 2
- 238000000302 molecular modelling Methods 0.000 description 2
- 201000006938 muscular dystrophy Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 238000006384 oligomerization reaction Methods 0.000 description 2
- 238000009806 oophorectomy Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-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
- SPSSULHKWOKEEL-UHFFFAOYSA-N 2,4,6-trinitrotoluene Chemical compound CC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O SPSSULHKWOKEEL-UHFFFAOYSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N 2-mercaptoethanol Substances OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101100161418 Arabidopsis thaliana AAP8 gene Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283725 Bos Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 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 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102220554990 HHIP-like protein 1_K40S_mutation Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001137510 Homo sapiens Outer dynein arm-docking complex subunit 2 Proteins 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 101710192606 Latent membrane protein 2 Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 101710167839 Morphogenetic protein Proteins 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 102000010410 Nogo Proteins Human genes 0.000 description 1
- 108010077641 Nogo Proteins Proteins 0.000 description 1
- 241000006416 Notata Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102100035706 Outer dynein arm-docking complex subunit 2 Human genes 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000028872 Progressive muscular dystrophy Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- SPUUKOIOZNVGHK-UHFFFAOYSA-N SSSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSSS SPUUKOIOZNVGHK-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101150095510 TMEM35A gene Proteins 0.000 description 1
- 101710109576 Terminal protein Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 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
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000000523 Type II Activin Receptors Human genes 0.000 description 1
- 108010041546 Type II Activin Receptors Proteins 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 241001409553 Uredo Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 235000021053 average weight gain Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 230000034127 bone morphogenesis Effects 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000337 buffer salt Substances 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
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 229940099500 cystamine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- ARYLBQOVLQRPOG-UHFFFAOYSA-L disodium;4-[4-[4-(3-carboxylatopropanoylamino)phenyl]sulfonylanilino]-4-oxobutanoate Chemical compound [Na+].[Na+].C1=CC(NC(=O)CCC(=O)[O-])=CC=C1S(=O)(=O)C1=CC=C(NC(=O)CCC([O-])=O)C=C1 ARYLBQOVLQRPOG-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000004222 ferrous gluconate Substances 0.000 description 1
- 210000002082 fibula Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 210000002758 humerus Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- ODLHGICHYURWBS-FOSILIAISA-N molport-023-220-444 Chemical compound CC(O)COC[C@@H]([C@@H]([C@H]([C@@H]1O)O)O[C@@H]2O[C@H]([C@H](O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O3)[C@@H](O)[C@@H]2O)COCC(O)C)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O)[C@H]3O[C@H]1COCC(C)O ODLHGICHYURWBS-FOSILIAISA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000025712 muscle attachment Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 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
- 210000002966 serum Anatomy 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 230000004096 skeletal muscle tissue growth Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 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
- 229940124597 therapeutic agent Drugs 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
- 210000002303 tibia Anatomy 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000000015 trinitrotoluene Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 101150103148 zar1 gene Proteins 0.000 description 1
Classifications
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P3/08—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90545907P | 2007-03-06 | 2007-03-06 | |
| US6547408P | 2008-02-11 | 2008-02-11 | |
| PCT/US2008/003119 WO2008109167A2 (en) | 2007-03-06 | 2008-03-06 | Variant activin receptor polypeptides and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200970810A1 EA200970810A1 (ru) | 2010-06-30 |
| EA020510B1 true EA020510B1 (ru) | 2014-11-28 |
Family
ID=39739001
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200970810A EA020510B1 (ru) | 2007-03-06 | 2008-03-06 | Модифицированные полипептиды рецептора активина и их применение |
| EA201490822A EA201490822A1 (ru) | 2007-03-06 | 2008-03-06 | Модифицированные полипептиды рецептора активина и их применение |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201490822A EA201490822A1 (ru) | 2007-03-06 | 2008-03-06 | Модифицированные полипептиды рецептора активина и их применение |
Country Status (29)
| Country | Link |
|---|---|
| US (5) | US7947646B2 (enExample) |
| EP (2) | EP3141605A1 (enExample) |
| JP (1) | JP5496682B2 (enExample) |
| KR (5) | KR20090127146A (enExample) |
| CN (2) | CN101679980B8 (enExample) |
| AR (1) | AR065611A1 (enExample) |
| AU (1) | AU2008223338C9 (enExample) |
| BR (1) | BRPI0808332A2 (enExample) |
| CA (1) | CA2679841C (enExample) |
| CL (2) | CL2008000664A1 (enExample) |
| CR (2) | CR11054A (enExample) |
| CY (1) | CY1118857T1 (enExample) |
| DK (1) | DK2132314T3 (enExample) |
| EA (2) | EA020510B1 (enExample) |
| ES (1) | ES2613043T3 (enExample) |
| HR (1) | HRP20170323T1 (enExample) |
| HU (1) | HUE032260T2 (enExample) |
| IL (2) | IL200605A (enExample) |
| LT (1) | LT2132314T (enExample) |
| MX (3) | MX389715B (enExample) |
| NZ (1) | NZ579369A (enExample) |
| PE (3) | PE20130615A1 (enExample) |
| PH (1) | PH12013502308A1 (enExample) |
| PL (1) | PL2132314T3 (enExample) |
| PT (1) | PT2132314T (enExample) |
| RS (1) | RS55726B1 (enExample) |
| SI (1) | SI2132314T1 (enExample) |
| TW (3) | TW201718635A (enExample) |
| WO (1) | WO2008109167A2 (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2561048T3 (es) | 2004-07-23 | 2016-02-24 | Acceleron Pharma Inc. | Polipéptidos del receptor ActRII |
| ES2533464T3 (es) | 2005-10-06 | 2015-04-10 | Eli Lilly And Company | Anticuerpos anti-miostatina |
| UA92504C2 (en) | 2005-10-12 | 2010-11-10 | Эли Лилли Энд Компани | Anti-myostatin monoclonal antibody |
| US8067562B2 (en) | 2005-11-01 | 2011-11-29 | Amgen Inc. | Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1 |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| ME00380B (me) | 2005-11-23 | 2011-10-10 | Acceleron Pharma Inc | Amtagonisti aktivin-actriia i primjene za stimulaciju rasta kosti |
| UA98308C2 (en) | 2006-09-05 | 2012-05-10 | Эли Лилли Энд Компани | Anti-myostatin antibody |
| CN104524548A (zh) | 2006-12-18 | 2015-04-22 | 阿塞勒隆制药公司 | 活化素-actrii拮抗剂及在提高红细胞水平中的用途 |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| US9526759B2 (en) | 2007-02-01 | 2016-12-27 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for treating or preventing breast cancer |
| TW201940502A (zh) | 2007-02-02 | 2019-10-16 | 美商艾瑟勒朗法瑪公司 | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 |
| KR101672156B1 (ko) | 2007-02-09 | 2016-11-02 | 악셀레론 파마 인코포레이티드 | 액티빈-ＡｃｔＲⅡＡ 길항제 및 암 환자에서 골 생장을 촉진시키기 위한 이의 용도 |
| US8501678B2 (en) | 2007-03-06 | 2013-08-06 | Atara Biotherapeutics, Inc. | Variant activin receptor polypeptides and uses thereof |
| TW201718635A (zh) * | 2007-03-06 | 2017-06-01 | 安美基公司 | 變異之活動素受體多肽及其用途 |
| CN107412734A (zh) | 2007-09-18 | 2017-12-01 | 阿塞勒隆制药公司 | 活化素‑actriia拮抗剂和减少或抑制fsh分泌的用途 |
| LT3750552T (lt) | 2008-08-14 | 2023-06-26 | Acceleron Pharma Inc. | Gdf gaudyklės |
| 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 |
| AU2016210719B2 (en) * | 2008-11-26 | 2018-03-29 | Amgen Inc. | Variants of activin IIB receptor polypeptides and uses thereof |
| KR20170105124A (ko) | 2008-11-26 | 2017-09-18 | 암젠 인크 | 액티빈 ｉｉｂ 수용체 폴리펩타이드의 변이체 및 이의 용도 |
| AU2013216639B2 (en) * | 2008-11-26 | 2016-05-05 | Amgen Inc. | Variants of activin IIB receptor polypeptides and uses thereof |
| CA2749544A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| EA027071B1 (ru) | 2009-04-27 | 2017-06-30 | Новартис Аг | АНТИТЕЛО К ActRIIB И СОДЕРЖАЩАЯ ЕГО КОМПОЗИЦИЯ |
| MX385318B (es) | 2009-06-08 | 2025-03-18 | Acceleron Pharma Inc | Metodos para aumentar adipocitos termogenicos. |
| JP2012529294A (ja) | 2009-06-12 | 2012-11-22 | アクセルロン ファーマ， インコーポレイテッド | 切断型ＡｃｔＲＩＩＢ−Ｆｃ融合タンパク質 |
| US20110129469A1 (en) | 2009-11-03 | 2011-06-02 | Acceleron Pharma Inc. | Methods for treating fatty liver disease |
| EP2501400B1 (en) | 2009-11-17 | 2017-11-01 | Acceleron Pharma, Inc. | Actriib proteins and variants and uses therefore relating to utrophin induction for muscular dystrophy therapy |
| JO3340B1 (ar) | 2010-05-26 | 2019-03-13 | Regeneron Pharma | مضادات حيوية لـعامل تمايز النمو 8 البشري |
| SG187867A1 (en) | 2010-08-16 | 2013-03-28 | Amgen Inc | Antibodies that bind myostatin, compositions and methods |
| WO2012064771A1 (en) | 2010-11-08 | 2012-05-18 | Acceleron Pharma, Inc. | Actriia binding agents and uses thereof |
| AU2010363656C1 (en) | 2010-11-12 | 2015-07-30 | Colgate-Palmolive Company | Oral care product and methods of use and manufacture thereof |
| JP6472999B2 (ja) * | 2011-07-01 | 2019-02-20 | ノバルティス アーゲー | 代謝障害を治療するための方法 |
| US8765385B2 (en) | 2011-10-27 | 2014-07-01 | Ravindra Kumar | Method of detection of neutralizing anti-actriib antibodies |
| RS56796B1 (sr) | 2011-11-14 | 2018-04-30 | Regeneron Pharma | Kompozicije i postupci za uvećanje mišićne mase i jačine mišića specifičnim antagonizovanjem gdf8 i/ili aktivina a |
| CN104379159A (zh) * | 2011-12-19 | 2015-02-25 | 安姆根公司 | 变体激活素受体多肽,单独或与化疗结合,及其用途 |
| WO2013142114A1 (en) | 2012-03-19 | 2013-09-26 | The Brigham And Women's Hosptial, Inc. | Growth differentiation factor (gdf) for treatment of diastolic heart failure |
| JP2015525230A (ja) | 2012-06-11 | 2015-09-03 | アムジエン・インコーポレーテツド | デュアル受容体アンタゴニスト性抗原結合タンパク質およびその使用 |
| JP6401172B2 (ja) | 2012-10-24 | 2018-10-10 | セルジーン コーポレイション | 貧血の治療方法 |
| RU2018145985A (ru) | 2012-11-02 | 2019-02-18 | Селджин Корпорейшн | Антагонисты активина-actrii и их применение для лечения нарушений костной ткани и других нарушений |
| AU2014212014A1 (en) | 2013-02-01 | 2015-08-27 | Amgen Inc. | Administration of an anti-activin-A compound to a subject |
| EA201591825A1 (ru) * | 2013-03-15 | 2016-05-31 | Амген Инк. | Антагонизм миостатина у субъектов - людей |
| ES2924479T3 (es) | 2013-04-08 | 2022-10-07 | Harvard College | Composiciones para rejuvenecer las células madre del músculo esquelético |
| TW201920262A (zh) | 2013-07-30 | 2019-06-01 | 美商再生元醫藥公司 | 抗活化素ａ之抗體及其用途 |
| US10017566B2 (en) | 2013-11-12 | 2018-07-10 | The Brigham And Women's Hospital, Inc. | Growth differentiation factor (GDF) for treatment of diastolic heart failure |
| KR20170035891A (ko) * | 2014-06-13 | 2017-03-31 | 산타 마리아 바이오테라퓨틱스, 인코포레이티드 | 제형화된 수용체 폴리펩타이드 및 관련 방법 |
| TN2016000553A1 (en) | 2014-06-13 | 2018-04-04 | Acceleron Pharma Inc | Methods and compositions for treating ulcers |
| MA41052A (fr) * | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| DK3227675T3 (da) | 2014-12-03 | 2023-05-30 | Celgene Corp | Activin-actrii-antagonister og anvendelser til behandling af myelodysplastisk syndrom |
| EP3229907A1 (en) * | 2014-12-08 | 2017-10-18 | Novartis AG | Myostatin or activin antagonists for the treatment of sarcopenia |
| WO2016128523A1 (en) | 2015-02-12 | 2016-08-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the responsiveness of a patient affected with malignant hematological disease to chemotherapy treatment and methods of treatment of such disease |
| US9744985B2 (en) | 2015-02-17 | 2017-08-29 | Hyundai Motor Company | Rack bar unit of vehicle steering device |
| MA41919A (fr) | 2015-04-06 | 2018-02-13 | Acceleron Pharma Inc | Hétéromultimères alk4:actriib et leurs utilisations |
| HK1250373A1 (zh) | 2015-04-06 | 2018-12-14 | Acceleron Pharma Inc. | Alk7:actriib异多聚体和其用途 |
| MD3280727T2 (ro) | 2015-04-06 | 2021-06-30 | Acceleron Pharma Inc | Proteine de fuziune ale receptorului de tip I și de tip II cu un singur braț și utilizările acestora |
| JP6877357B2 (ja) | 2015-04-15 | 2021-05-26 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｇｄｆ８阻害剤を用いて、強度及び機能を増加させる方法 |
| DK3286206T3 (da) * | 2015-04-22 | 2021-05-03 | Biogen Ma Inc | Hidtil ukendte hybride actriib-ligand-trap-proteiner til behandling af muskelsvindsygdomme |
| RU2651776C2 (ru) * | 2015-12-01 | 2018-04-23 | Общество с ограниченной ответственностью "Международный биотехнологический центр "Генериум" ("МБЦ "Генериум") | Биспецифические антитела против cd3*cd19 |
| CN116059320A (zh) | 2016-01-06 | 2023-05-05 | 哈佛学院校长同事会 | 使用gdf11的治疗防止体重增加、提高葡萄糖耐量并减轻脂肪肝 |
| HRP20241557T1 (hr) | 2016-03-10 | 2025-05-23 | Acceleron Pharma Inc. | Proteini koji vezuju receptor aktivina tipa 2 i njihova uporaba |
| US10934532B2 (en) | 2016-10-05 | 2021-03-02 | Acceleron Pharma Inc. | ALK4.ActRIIB heteromultimers |
| JOP20190085A1 (ar) * | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| WO2018089715A1 (en) | 2016-11-10 | 2018-05-17 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| KR20250059538A (ko) | 2017-11-09 | 2025-05-02 | 케로스 테라퓨틱스, 인크. | 액티빈 수용체 유형 iia 변이체 및 그의 사용 방법 |
| JP7510875B2 (ja) | 2018-01-12 | 2024-07-04 | ケロス セラピューティクス インコーポレイテッド | アクチビンｉｉｂ型受容体変異体および同変異体を含む医薬組成物 |
| US11248044B2 (en) | 2018-03-01 | 2022-02-15 | Regeneron Pharmaceuticals, Inc. | Methods for altering body composition by administering a GDF8 inhibitor and an Activin A inhibitor |
| KR20250133994A (ko) | 2018-05-09 | 2025-09-09 | 케로스 테라퓨틱스, 인크. | 액티빈 수용체 유형 iia 변이체 및 그의 사용 방법 |
| EP4121088A4 (en) | 2020-03-20 | 2024-07-03 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| KR20230004515A (ko) | 2020-03-20 | 2023-01-06 | 케로스 테라퓨틱스, 인크. | 액티빈 수용체 유형 ii 키메라 및 이의 사용 방법 |
| WO2023108137A1 (en) * | 2021-12-10 | 2023-06-15 | Biogen Ma Inc. | Modified actriib proteins and methods of use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004039948A2 (en) * | 2002-10-25 | 2004-05-13 | Wyeth | Actriib fusion polypeptides and uses therefor |
| US20060034831A1 (en) * | 2004-08-12 | 2006-02-16 | Wyeth | Combination therapy for diabetes, obesity and cardiovascular diseases using GDF-8 inhibitors |
| WO2007053775A1 (en) * | 2005-11-01 | 2007-05-10 | Amgen Inc. | Novel activin receptor and uses thereof |
| WO2008097541A2 (en) * | 2007-02-02 | 2008-08-14 | Acceleron Pharma Inc. | Variants derived from actriib and uses therefor |
Family Cites Families (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2899886A (en) * | 1959-08-18 | rodth | ||
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| JPS5349966A (en) | 1976-10-18 | 1978-05-06 | Hitachi Ltd | Manufacture of semiconductor integrated circuit |
| US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4411993A (en) | 1981-04-29 | 1983-10-25 | Steven Gillis | Hybridoma antibody which inhibits interleukin 2 activity |
| USRE32011E (en) | 1981-12-14 | 1985-10-22 | Scripps Clinic And Research Foundation | Ultrapurification of factor VIII using monoclonal antibodies |
| DE3374837D1 (en) | 1982-02-17 | 1988-01-21 | Ciba Geigy Ag | Lipids in the aqueous phase |
| US4543439A (en) | 1982-12-13 | 1985-09-24 | Massachusetts Institute Of Technology | Production and use of monoclonal antibodies to phosphotyrosine-containing proteins |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
| DE3474511D1 (en) | 1983-11-01 | 1988-11-17 | Terumo Corp | Pharmaceutical composition containing urokinase |
| US4902614A (en) | 1984-12-03 | 1990-02-20 | Teijin Limited | Monoclonal antibody to human protein C |
| US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
| US5750375A (en) | 1988-01-22 | 1998-05-12 | Zymogenetics, Inc. | Methods of producing secreted receptor analogs and biologically active dimerized polypeptide fusions |
| US5567584A (en) | 1988-01-22 | 1996-10-22 | Zymogenetics, Inc. | Methods of using biologically active dimerized polypeptide fusions to detect PDGF |
| JP2877509B2 (ja) | 1989-05-19 | 1999-03-31 | アムジエン・インコーポレーテツド | メタロプロテイナーゼ阻害剤 |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US6565841B1 (en) | 1991-03-15 | 2003-05-20 | Amgen, Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| US20050186593A1 (en) * | 1991-05-10 | 2005-08-25 | The Salk Institute For Biological Studies | Cloning and recombinant production of CRF receptor(s) |
| US6162896A (en) * | 1991-05-10 | 2000-12-19 | The Salk Institute For Biological Studies | Recombinant vertebrate activin receptors |
| US5885794A (en) * | 1991-05-10 | 1999-03-23 | The Salk Institute For Biological Studies | Recombinant production of vertebrate activin receptor polypeptides and identification of receptor DNAs in the activin/TGF-β superfamily |
| EP0521187B1 (fr) * | 1991-07-05 | 1995-11-02 | Societe Des Produits Nestle S.A. | Dispositif d'extraction de cartouches adaptable à toute machine espresso |
| DK0521510T3 (da) * | 1991-07-05 | 1997-05-12 | Nestle Sa | Stiv kaffepatron og fremgangsmåde til fremstilling heraf |
| US5470582A (en) | 1992-02-07 | 1995-11-28 | Syntex (U.S.A.) Inc. | Controlled delivery of pharmaceuticals from preformed porous polymeric microparticles |
| US6153407A (en) | 1992-07-28 | 2000-11-28 | Beth Israel Deaconess Medical Center | Erythropoietin DNA having modified 5' and 3' sequences and its use to prepare EPO therapeutics |
| US5837821A (en) | 1992-11-04 | 1998-11-17 | City Of Hope | Antibody construct |
| GB9223377D0 (en) | 1992-11-04 | 1992-12-23 | Medarex Inc | Humanized antibodies to fc receptors for immunoglobulin on human mononuclear phagocytes |
| US6607884B1 (en) | 1993-03-19 | 2003-08-19 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-8 |
| US5994618A (en) | 1997-02-05 | 1999-11-30 | Johns Hopkins University School Of Medicine | Growth differentiation factor-8 transgenic mice |
| ES2201076T3 (es) | 1993-03-19 | 2004-03-16 | The Johns Hopkins University School Of Medicine | Factor-8 de diferenciacion del crecimiento. |
| 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 |
| CA2187902A1 (en) | 1994-04-29 | 1995-11-09 | Peter Ten Dijke | Morphogenic protein-specific cell surface receptors and uses therefor |
| 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 |
| 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 |
| US6472179B2 (en) | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| ATE362534T2 (de) | 1998-11-13 | 2007-06-15 | Immunex Corp | Menschliche tslp nukleinsäuren und polypeptide |
| EP1147413B1 (en) | 1999-01-21 | 2006-04-05 | Metamorphix, Inc. | Growth differentiation factor inhibitors and uses therefor |
| JP2000262405A (ja) * | 1999-03-18 | 2000-09-26 | Soc Prod Nestle Sa | 飲料抽出用密封カートリッジ |
| JP4487376B2 (ja) | 2000-03-31 | 2010-06-23 | 味の素株式会社 | 腎疾患治療剤 |
| TWI236360B (en) * | 2000-06-30 | 2005-07-21 | Nestle Sa | Capsule cage |
| US6812339B1 (en) * | 2000-09-08 | 2004-11-02 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
| EP1190959B1 (fr) * | 2000-09-26 | 2004-03-31 | Societe Des Produits Nestle S.A. | Cartouche fermée pour la confection d'une boisson, prévue pour être extraite sous pression |
| EP1203554A1 (fr) * | 2000-11-03 | 2002-05-08 | Societe Des Produits Nestle S.A. | Dispositif pour l'extraction d'une substance alimentaire contenue dans un élément de recharge |
| TR200402491T4 (tr) * | 2000-11-28 | 2004-12-21 | Societe Des Produits Nestle S.A. | Süzme tertibatı. |
| US6786134B2 (en) * | 2002-02-07 | 2004-09-07 | The Coca-Cola Company | Coffee and tea dispenser |
| US20050188854A1 (en) * | 2002-02-07 | 2005-09-01 | The Coca-Cola Co. | Coffee and tea dispenser |
| GB0209896D0 (en) | 2002-04-30 | 2002-06-05 | Molmed Spa | Conjugate |
| FR2842092B1 (fr) * | 2002-07-12 | 2004-12-24 | Seb Sa | Machine a cafe fonctionnant avec des doses |
| KR20130036378A (ko) | 2002-12-20 | 2013-04-11 | 암겐 인코포레이티드 | 미오스타틴을 저해하는 결합제 |
| WO2004108157A2 (en) | 2003-06-02 | 2004-12-16 | Wyeth | Use of myostatin (gdf8) inhibitors in conjunction with corticosteroids for treating neuromuscular disorders |
| US20060196364A1 (en) * | 2003-07-22 | 2006-09-07 | The Coca-Cola Company | Coffee & Tea Pod |
| US8327754B2 (en) * | 2003-07-22 | 2012-12-11 | The Coca-Cola Company | Coffee and tea pod |
| EP1663182B2 (en) | 2003-09-12 | 2019-11-20 | Amgen Inc. | RAPID DISSOLUTION FORMULATION OF CINACALCET HCl |
| US7074445B2 (en) * | 2003-10-30 | 2006-07-11 | Frito-Lay North America, Inc. | Method for adhering large seasoning bits to a food substrate |
| JP2007531513A (ja) | 2003-11-13 | 2007-11-08 | ハンミ ファーム．インダストリー カンパニー リミテッド | 薬物のキャリアとして有用なＩｇＧＦｃ断片およびその製造方法 |
| US8110665B2 (en) | 2003-11-13 | 2012-02-07 | Hanmi Holdings Co., Ltd. | Pharmaceutical composition comprising an immunoglobulin FC region as a carrier |
| GB2411106B (en) * | 2004-02-17 | 2006-11-22 | Kraft Foods R & D Inc | Cartridge for the preparation of beverages |
| JP5036533B2 (ja) | 2004-04-23 | 2012-09-26 | アムジエン・インコーポレーテツド | 持続放出製剤 |
| ES2561048T3 (es) | 2004-07-23 | 2016-02-24 | Acceleron Pharma Inc. | Polipéptidos del receptor ActRII |
| GB2416480B (en) * | 2004-07-27 | 2007-12-27 | Kraft Foods R & D Inc | A system for the preparation of beverages |
| CN101103045B (zh) | 2004-09-24 | 2015-11-25 | 安姆根有限公司 | 修饰的Fc分子 |
| EP1640756A1 (en) * | 2004-09-27 | 2006-03-29 | Barco N.V. | Methods and systems for illuminating |
| KR100754667B1 (ko) | 2005-04-08 | 2007-09-03 | 한미약품 주식회사 | 비펩타이드성 중합체로 개질된 면역글로불린 Ｆｃ 단편 및이를 포함하는 약제학적 조성물 |
| HN2006031275A (es) | 2005-09-07 | 2010-10-29 | Amgen Fremont Inc | Anticuerpos monoclonales humanos para la quinasa-1 tipo receptor de activina |
| DE602005008610D1 (de) * | 2005-10-14 | 2008-09-11 | Nestec Sa | Kapsel zur Bereitung eines Getränks |
| US20080014860A1 (en) * | 2006-07-14 | 2008-01-17 | Lynn Byron Heitman | Method and apparatus for eliminating register boxes, improving penetration sealing, improving airflow and reducing the labor costs to install ceiling registers |
| CL2007002567A1 (es) | 2006-09-08 | 2008-02-01 | Amgen Inc | Proteinas aisladas de enlace a activina a humana. |
| CN104524548A (zh) | 2006-12-18 | 2015-04-22 | 阿塞勒隆制药公司 | 活化素-actrii拮抗剂及在提高红细胞水平中的用途 |
| TW201718635A (zh) | 2007-03-06 | 2017-06-01 | 安美基公司 | 變異之活動素受體多肽及其用途 |
| US8501678B2 (en) | 2007-03-06 | 2013-08-06 | Atara Biotherapeutics, Inc. | Variant activin receptor polypeptides and uses thereof |
| US8318135B2 (en) | 2007-03-19 | 2012-11-27 | National Research Council Of Canada | Antagonist of ligands and uses thereof |
| US8431175B2 (en) * | 2007-06-05 | 2013-04-30 | Nestec S.A. | Method for preparing a beverage or food liquid and system using brewing centrifugal force |
| JP5082676B2 (ja) * | 2007-08-23 | 2012-11-28 | 株式会社サタケ | 光学式穀物選別機 |
| CN107412734A (zh) | 2007-09-18 | 2017-12-01 | 阿塞勒隆制药公司 | 活化素‑actriia拮抗剂和减少或抑制fsh分泌的用途 |
| KR101871510B1 (ko) | 2008-06-26 | 2018-06-26 | 악셀레론 파마 인코포레이티드 | 액티빈-ａｃｔｒｉｉａ 길항물질을 투약하는 방법 및 치료된 환자의 모니터링 |
| US8857317B2 (en) * | 2008-07-08 | 2014-10-14 | Nestec S.A. | Portion-controlled nutrition system and method using capsules |
| US8151694B2 (en) * | 2008-08-01 | 2012-04-10 | Keurig, Incorporated | Beverage forming apparatus with centrifugal pump |
| 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 |
| LT3750552T (lt) | 2008-08-14 | 2023-06-26 | Acceleron Pharma Inc. | Gdf gaudyklės |
| ES2550307T3 (es) * | 2008-09-02 | 2015-11-06 | Nestec S.A. | Dispositivo de producción controlada de bebidas usando fuerzas centrífugas |
| KR20170105124A (ko) | 2008-11-26 | 2017-09-18 | 암젠 인크 | 액티빈 ｉｉｂ 수용체 폴리펩타이드의 변이체 및 이의 용도 |
| CA2749544A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| EA027071B1 (ru) | 2009-04-27 | 2017-06-30 | Новартис Аг | АНТИТЕЛО К ActRIIB И СОДЕРЖАЩАЯ ЕГО КОМПОЗИЦИЯ |
| MX385318B (es) | 2009-06-08 | 2025-03-18 | Acceleron Pharma Inc | Metodos para aumentar adipocitos termogenicos. |
| US20120295814A1 (en) | 2010-01-08 | 2012-11-22 | The Brigham And Women's Hospital, Inc. | CA-125 Immune Complexes as Biomarkers of Ovarian Cancer |
| MX2011011596A (es) | 2010-03-31 | 2012-02-01 | Keryx Biopharmaceuticals Inc | Perifosina y capecitabina como un tratamiento combinado para cancer. |
| WO2012064771A1 (en) | 2010-11-08 | 2012-05-18 | Acceleron Pharma, Inc. | Actriia binding agents and uses thereof |
| CN104379159A (zh) | 2011-12-19 | 2015-02-25 | 安姆根公司 | 变体激活素受体多肽,单独或与化疗结合,及其用途 |
| WO2013106715A1 (en) | 2012-01-13 | 2013-07-18 | Allergan, Inc. | Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation |
| US9401875B2 (en) | 2012-06-01 | 2016-07-26 | Nippon Telegraph And Telephone Corporation | Packet transfer processing method and packet transfer processing device |
| US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
-
2008
- 2008-03-05 TW TW105129851A patent/TW201718635A/zh unknown
- 2008-03-05 US US12/074,877 patent/US7947646B2/en active Active
- 2008-03-05 TW TW103117408A patent/TWI573802B/zh not_active IP Right Cessation
- 2008-03-05 TW TW097107642A patent/TWI454479B/zh not_active IP Right Cessation
- 2008-03-06 PE PE2012002108A patent/PE20130615A1/es not_active Application Discontinuation
- 2008-03-06 DK DK08742032.9T patent/DK2132314T3/en active
- 2008-03-06 EA EA200970810A patent/EA020510B1/ru not_active IP Right Cessation
- 2008-03-06 AU AU2008223338A patent/AU2008223338C9/en active Active
- 2008-03-06 JP JP2009552758A patent/JP5496682B2/ja active Active
- 2008-03-06 CA CA2679841A patent/CA2679841C/en active Active
- 2008-03-06 KR KR1020097020320A patent/KR20090127146A/ko not_active Ceased
- 2008-03-06 AR ARP080100918A patent/AR065611A1/es not_active Application Discontinuation
- 2008-03-06 SI SI200831764A patent/SI2132314T1/sl unknown
- 2008-03-06 MX MX2017005686A patent/MX389715B/es unknown
- 2008-03-06 KR KR1020157003616A patent/KR101633727B1/ko not_active Expired - Fee Related
- 2008-03-06 WO PCT/US2008/003119 patent/WO2008109167A2/en not_active Ceased
- 2008-03-06 EP EP16194631.4A patent/EP3141605A1/en not_active Withdrawn
- 2008-03-06 CL CL200800664A patent/CL2008000664A1/es unknown
- 2008-03-06 KR KR1020147010346A patent/KR101633728B1/ko not_active Expired - Fee Related
- 2008-03-06 MX MX2015002054A patent/MX348286B/es unknown
- 2008-03-06 CN CN200880007116.0A patent/CN101679980B8/zh not_active Expired - Fee Related
- 2008-03-06 KR KR1020127008467A patent/KR101428344B1/ko not_active Expired - Fee Related
- 2008-03-06 CN CN201610218042.1A patent/CN105924516A/zh active Pending
- 2008-03-06 PT PT87420329T patent/PT2132314T/pt unknown
- 2008-03-06 HU HUE08742032A patent/HUE032260T2/en unknown
- 2008-03-06 EP EP08742032.9A patent/EP2132314B1/en active Active
- 2008-03-06 EA EA201490822A patent/EA201490822A1/ru unknown
- 2008-03-06 ES ES08742032.9T patent/ES2613043T3/es active Active
- 2008-03-06 PE PE2008000436A patent/PE20081804A1/es not_active Application Discontinuation
- 2008-03-06 RS RS20170192A patent/RS55726B1/sr unknown
- 2008-03-06 NZ NZ579369A patent/NZ579369A/en not_active IP Right Cessation
- 2008-03-06 PL PL08742032T patent/PL2132314T3/pl unknown
- 2008-03-06 HR HRP20170323TT patent/HRP20170323T1/hr unknown
- 2008-03-06 BR BRPI0808332-0A patent/BRPI0808332A2/pt not_active IP Right Cessation
- 2008-03-06 MX MX2009009495A patent/MX2009009495A/es active IP Right Grant
- 2008-03-06 KR KR1020167016449A patent/KR20160075861A/ko not_active Abandoned
- 2008-03-06 PE PE2017001328A patent/PE20171325A1/es not_active Application Discontinuation
- 2008-03-06 LT LTEP08742032.9T patent/LT2132314T/lt unknown
-
2009
- 2009-08-27 IL IL200605A patent/IL200605A/en not_active IP Right Cessation
- 2009-10-05 CR CR11054A patent/CR11054A/es not_active Application Discontinuation
-
2011
- 2011-04-05 US US13/080,515 patent/US8716459B2/en active Active
-
2013
- 2013-11-11 PH PH12013502308A patent/PH12013502308A1/en unknown
-
2014
- 2014-03-11 US US14/204,460 patent/US9447165B2/en active Active
-
2015
- 2015-02-24 CR CR20150094A patent/CR20150094A/es unknown
- 2015-10-23 CL CL2015003139A patent/CL2015003139A1/es unknown
-
2016
- 2016-06-02 US US15/171,944 patent/US9809638B2/en active Active
- 2016-10-13 IL IL248322A patent/IL248322A0/en unknown
-
2017
- 2017-02-22 CY CY20171100238T patent/CY1118857T1/el unknown
- 2017-09-25 US US15/714,726 patent/US10407487B2/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004039948A2 (en) * | 2002-10-25 | 2004-05-13 | Wyeth | Actriib fusion polypeptides and uses therefor |
| US20040223966A1 (en) * | 2002-10-25 | 2004-11-11 | Wolfman Neil M. | ActRIIB fusion polypeptides and uses therefor |
| US20060034831A1 (en) * | 2004-08-12 | 2006-02-16 | Wyeth | Combination therapy for diabetes, obesity and cardiovascular diseases using GDF-8 inhibitors |
| WO2006020884A2 (en) * | 2004-08-12 | 2006-02-23 | Wyeth | Combination therapy for diabetes, obesity, and cardiovascular diseases using gdf-8 inhibitors |
| WO2007053775A1 (en) * | 2005-11-01 | 2007-05-10 | Amgen Inc. | Novel activin receptor and uses thereof |
| WO2008097541A2 (en) * | 2007-02-02 | 2008-08-14 | Acceleron Pharma Inc. | Variants derived from actriib and uses therefor |
Non-Patent Citations (5)
| Title |
|---|
| ATTISANO L. ET AL.: "Novel activin receptors: Distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors" CELL, CELL PRESS, CAMBRIDGE, NA, US, vol. 68, no. 1, 10 January 1992 (1992-01-10), pages 97-108, XP024244697 ISSN: 0092-8674 [retrieved on 1992-01-10] the whole document * |
| GRAY P.C. ET AL.: "Identification of a binding site on the type II activin receptor, for activin and inhibin". JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOCHEMICAL BIOLOGISTS, BIRMINGHAM,; US, vol. 275, no. 5, 4 February 2000 (2000-02-04), pages 3206-3212, XP002366136 ISSN: 0021-9258 the whole document * |
| HARRISON CRAIG A. ET AL.: "An activin mutant with disrupted ALK4 binding blocks signaling via type II receptors". JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOCHEMICAL BIOLOGISTS, BIRMINGHAM,; US, 2 July 2004 (2004-07-02), pages 28036-28044, XP002372283 ISSN: 0021-9258 cited in the application the whole document * |
| HILDEN K. ET AL.: "Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor". BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 83, no. 8, 1 January 1994 (1994-01-01), pages 2163-2170, XP002240644 ISSN: 0006-4971 the whole document * |
| OH S. PAUL ET AL.: "Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning". GENES & DEVELOPMENT 1 NOV 2002, vol. 16, no. 21, 1 November 2002 (2002-11-01), pages 2749-2754, XP002516633 ISSN: 0890-9369 cited in the application the whole document * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA020510B1 (ru) | Модифицированные полипептиды рецептора активина и их применение | |
| JP6542433B2 (ja) | 単独でのまたは化学療法と組み合わされた変異アクチビン受容体ポリペプチド、およびその使用 | |
| ES2401805T3 (es) | Antagonistas de activina-ActRlla y usos para promover el crecimiento óseo | |
| TWI432449B (zh) | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 | |
| JP2021164472A (ja) | 切断型ＡｃｔＲＩＩＢ−Ｆｃ融合タンパク質 | |
| JP2021095416A (ja) | 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 | |
| HUE032090T2 (en) | Stabilized variants of activin IIB receptor | |
| JP2013177390A (ja) | 乳癌を治療または予防するためのアクチビンＡｃｔＲＩＩａアンタゴニストおよび使用 | |
| HUE035264T2 (hu) | Pirrolo[2,3-d]pirimidinil-, pirrolo[2,3-b]pirazinil- és pirrolo[2,3-d]-piridinil- akrilamidok | |
| EP3604343B1 (en) | Fusion protein, preparation method therefor and use thereof | |
| EA024507B1 (ru) | Хорошо растворимые лептины | |
| ES2796743T3 (es) | Un polipéptido de receptor de factor de crecimiento de fibroblastos 3 (FGR3) soluble para su uso en la prevención o tratamiento de trastornos de retraso del crecimiento esquelético | |
| CA2875069C (en) | Agent for prophylactic and/or therapeutic treatment of peripheral neuropathic pain caused by anticancer agent | |
| JP2021505593A (ja) | Ｈｍ−３融合タンパク質及びその適用 | |
| US20220280594A1 (en) | Application of polypeptide or derivative thereof | |
| CA3087835A1 (en) | Modified protein | |
| ES2974646T3 (es) | Complejos peptídicos HLA-DR/CII para el tratamiento de la artritis | |
| CN109715191A (zh) | 将赘生性细胞转化成非赘生性细胞的药物缔合物及其用途 | |
| KR102127218B1 (ko) | 뇌 신경 교종 치료용 약물 제조에서의 화합물의 용도 | |
| KR20250010014A (ko) | Utr을 포함하는 핵산 작제물 및 이의 용도 | |
| EA008253B1 (ru) | Антагонисты nogo-рецептора | |
| ES2390967T3 (es) | Epítopo/péptido reconocido por LTC específico para Ep-CAM con restricción por ALH-A2402 y su utilización | |
| CN104056277A (zh) | Mlh1基因或其表达产物在dkk4高表达的结直肠癌中的应用 | |
| CN107513107A (zh) | 抗肿瘤融合蛋白及其制法和应用 | |
| EP2168589A1 (en) | INSULIN SECRETION INDUCER, AND ACCELERATOR OF INCREASE IN PANCREATIC ß-CELLS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |