CA2986432A1 - In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps - Google Patents
In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand trapsInfo
- Publication number
- CA2986432A1 CA2986432A1 CA2986432A CA2986432A CA2986432A1 CA 2986432 A1 CA2986432 A1 CA 2986432A1 CA 2986432 A CA2986432 A CA 2986432A CA 2986432 A CA2986432 A CA 2986432A CA 2986432 A1 CA2986432 A1 CA 2986432A1
- Authority
- CA
- Canada
- Prior art keywords
- fold
- level
- seq
- certain embodiments
- supernatant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 578
- 238000012606 in vitro cell culture Methods 0.000 title claims abstract description 384
- 208000005980 beta thalassemia Diseases 0.000 title claims abstract description 97
- 108010059616 Activins Proteins 0.000 title claims abstract description 76
- 239000000488 activin Substances 0.000 title claims abstract description 76
- 102000005606 Activins Human genes 0.000 title claims abstract description 10
- 239000003446 ligand Substances 0.000 title abstract description 20
- 230000011664 signaling Effects 0.000 claims abstract description 325
- 239000003112 inhibitor Substances 0.000 claims abstract description 307
- 238000012544 monitoring process Methods 0.000 claims abstract description 14
- 210000003013 erythroid precursor cell Anatomy 0.000 claims description 421
- 239000006228 supernatant Substances 0.000 claims description 364
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 140
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 136
- 229920001184 polypeptide Polymers 0.000 claims description 134
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 119
- 210000002536 stromal cell Anatomy 0.000 claims description 119
- 238000011282 treatment Methods 0.000 claims description 104
- 230000007423 decrease Effects 0.000 claims description 77
- 102100035716 Glycophorin-A Human genes 0.000 claims description 69
- 108091005902 Hemoglobin subunit alpha Proteins 0.000 claims description 68
- 102100031690 Erythroid transcription factor Human genes 0.000 claims description 67
- 101001066265 Homo sapiens Endothelial transcription factor GATA-2 Proteins 0.000 claims description 67
- 102100027685 Hemoglobin subunit alpha Human genes 0.000 claims description 66
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 claims description 66
- 102100031785 Endothelial transcription factor GATA-2 Human genes 0.000 claims description 65
- 101001066268 Homo sapiens Erythroid transcription factor Proteins 0.000 claims description 64
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 claims description 63
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 claims description 63
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims description 62
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 claims description 62
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 62
- 101000621061 Homo sapiens Serum paraoxonase/arylesterase 2 Proteins 0.000 claims description 62
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 claims description 61
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 61
- 102100032367 C-C motif chemokine 5 Human genes 0.000 claims description 61
- 108090000397 Caspase 3 Proteins 0.000 claims description 61
- 102000003952 Caspase 3 Human genes 0.000 claims description 61
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 61
- 102000003814 Interleukin-10 Human genes 0.000 claims description 61
- 108090000174 Interleukin-10 Proteins 0.000 claims description 61
- 108010002350 Interleukin-2 Proteins 0.000 claims description 61
- 108090001005 Interleukin-6 Proteins 0.000 claims description 61
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims description 60
- 108010055166 Chemokine CCL5 Proteins 0.000 claims description 60
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 claims description 60
- 108090001007 Interleukin-8 Proteins 0.000 claims description 60
- 102100022824 Serum paraoxonase/arylesterase 2 Human genes 0.000 claims description 60
- 108010002687 Survivin Proteins 0.000 claims description 60
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 claims description 59
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 59
- 108060004872 MIF Proteins 0.000 claims description 58
- 108010031102 heme oxygenase-2 Proteins 0.000 claims description 56
- -1 Bcl-xL Proteins 0.000 claims description 44
- 238000012258 culturing Methods 0.000 claims description 37
- 101000941598 Homo sapiens Complement C5 Proteins 0.000 claims description 33
- 239000003636 conditioned culture medium Substances 0.000 claims description 33
- 108020001507 fusion proteins Proteins 0.000 claims description 31
- 102000037865 fusion proteins Human genes 0.000 claims description 31
- 108020003175 receptors Proteins 0.000 claims description 28
- 210000001185 bone marrow Anatomy 0.000 claims description 14
- 230000004043 responsiveness Effects 0.000 claims description 13
- 210000005259 peripheral blood Anatomy 0.000 claims description 7
- 239000011886 peripheral blood Substances 0.000 claims description 7
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 6
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims description 6
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 claims description 4
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 claims 5
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 claims 5
- 108010057429 activin receptor type II-A Proteins 0.000 description 109
- 235000001014 amino acid Nutrition 0.000 description 107
- 150000007523 nucleic acids Chemical group 0.000 description 106
- 102100021886 Activin receptor type-2A Human genes 0.000 description 80
- 230000001965 increasing effect Effects 0.000 description 79
- 230000003247 decreasing effect Effects 0.000 description 77
- 210000004027 cell Anatomy 0.000 description 76
- 238000003556 assay Methods 0.000 description 71
- 150000001413 amino acids Chemical class 0.000 description 67
- 102100026818 Inhibin beta E chain Human genes 0.000 description 66
- 229940024606 amino acid Drugs 0.000 description 65
- 108090000623 proteins and genes Proteins 0.000 description 64
- 239000000203 mixture Substances 0.000 description 63
- 102000004169 proteins and genes Human genes 0.000 description 62
- 235000018102 proteins Nutrition 0.000 description 60
- 102100031506 Complement C5 Human genes 0.000 description 58
- 108700000707 bcl-2-Associated X Proteins 0.000 description 57
- 102000055102 bcl-2-Associated X Human genes 0.000 description 57
- 102000000588 Interleukin-2 Human genes 0.000 description 56
- 102000004889 Interleukin-6 Human genes 0.000 description 56
- 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 description 56
- 108700012411 TNFSF10 Proteins 0.000 description 56
- 102000039446 nucleic acids Human genes 0.000 description 56
- 108020004707 nucleic acids Proteins 0.000 description 56
- 102000004890 Interleukin-8 Human genes 0.000 description 55
- 102000034655 MIF Human genes 0.000 description 55
- 108050008367 Transmembrane emp24 domain-containing protein 7 Proteins 0.000 description 55
- 102100028008 Heme oxygenase 2 Human genes 0.000 description 54
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 54
- 101000891649 Homo sapiens Transcription elongation factor A protein-like 1 Proteins 0.000 description 53
- 230000027455 binding Effects 0.000 description 53
- 108020004999 messenger RNA Proteins 0.000 description 45
- 239000002299 complementary DNA Substances 0.000 description 34
- 101000596402 Mus musculus Neuronal vesicle trafficking-associated protein 1 Proteins 0.000 description 29
- 101000800539 Mus musculus Translationally-controlled tumor protein Proteins 0.000 description 29
- 102100028588 Protein ZNRD2 Human genes 0.000 description 29
- 101000781972 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Protein wos2 Proteins 0.000 description 29
- 101001009610 Toxoplasma gondii Dense granule protein 5 Proteins 0.000 description 29
- 102100040250 Transcription elongation factor A protein-like 1 Human genes 0.000 description 29
- 230000001419 dependent effect Effects 0.000 description 29
- 230000035772 mutation Effects 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 25
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 24
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 24
- 108091028043 Nucleic acid sequence Proteins 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 24
- 239000002243 precursor Substances 0.000 description 20
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 19
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 18
- 230000000875 corresponding effect Effects 0.000 description 18
- 238000002560 therapeutic procedure Methods 0.000 description 18
- 108700028369 Alleles Proteins 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 108010054147 Hemoglobins Proteins 0.000 description 13
- 102000001554 Hemoglobins Human genes 0.000 description 13
- 101000937269 Homo sapiens Activin receptor type-2B Proteins 0.000 description 13
- 210000003743 erythrocyte Anatomy 0.000 description 13
- 102000045412 human ACVR2B Human genes 0.000 description 13
- 101000970954 Homo sapiens Activin receptor type-2A Proteins 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 230000003833 cell viability Effects 0.000 description 12
- 230000004069 differentiation Effects 0.000 description 11
- 230000000925 erythroid effect Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 238000011529 RT qPCR Methods 0.000 description 10
- 239000000090 biomarker Substances 0.000 description 10
- 238000003501 co-culture Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 108010068323 Hemoglobin E Proteins 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 description 7
- 235000004279 alanine Nutrition 0.000 description 7
- 230000004075 alteration Effects 0.000 description 7
- 208000022806 beta-thalassemia major Diseases 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000004475 Arginine Substances 0.000 description 6
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- 230000004988 N-glycosylation Effects 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 235000018417 cysteine Nutrition 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 239000008215 water for injection Substances 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 108010044495 Fetal Hemoglobin Proteins 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 230000001464 adherent effect Effects 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000010437 erythropoiesis Effects 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 210000000689 upper leg Anatomy 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
- 101710199554 A protein Proteins 0.000 description 4
- 102220479051 CD59 glycoprotein_L79D_mutation Human genes 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 4
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 4
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 4
- 238000002655 chelation therapy Methods 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000012252 genetic analysis Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000000816 peptidomimetic Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 102220525561 Coiled-coil domain-containing protein 200_A24N_mutation Human genes 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108091006020 Fc-tagged proteins Proteins 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 3
- 101000896234 Homo sapiens Baculoviral IAP repeat-containing protein 5 Proteins 0.000 description 3
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 3
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 3
- 101000886562 Homo sapiens Growth/differentiation factor 8 Proteins 0.000 description 3
- 101001079615 Homo sapiens Heme oxygenase 2 Proteins 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 206010041660 Splenomegaly Diseases 0.000 description 3
- 208000002903 Thalassemia Diseases 0.000 description 3
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 3
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 108010023082 activin A Proteins 0.000 description 3
- 108010023079 activin B Proteins 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 229960000187 tissue plasminogen activator Drugs 0.000 description 3
- 102000018918 Activin Receptors Human genes 0.000 description 2
- 108010052946 Activin Receptors Proteins 0.000 description 2
- 102100027647 Activin receptor type-2B Human genes 0.000 description 2
- 206010060935 Alloimmunisation Diseases 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102220578645 Chorion-specific transcription factor GCMb_N65A_mutation Human genes 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 101150050927 Fcgrt gene Proteins 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 206010053759 Growth retardation Diseases 0.000 description 2
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 2
- 108010027616 Hemoglobin A2 Proteins 0.000 description 2
- 108091005886 Hemoglobin subunit gamma Proteins 0.000 description 2
- 102100038617 Hemoglobin subunit gamma-2 Human genes 0.000 description 2
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 2
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 2
- 101000793880 Homo sapiens Caspase-3 Proteins 0.000 description 2
- 101000944380 Homo sapiens Cyclin-dependent kinase inhibitor 1 Proteins 0.000 description 2
- 101001009007 Homo sapiens Hemoglobin subunit alpha Proteins 0.000 description 2
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 2
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 2
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 2
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 2
- 101000950847 Homo sapiens Macrophage migration inhibitory factor Proteins 0.000 description 2
- 101001011645 Homo sapiens Muellerian-inhibiting factor Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 101000851526 Homo sapiens Transmembrane emp24 domain-containing protein 7 Proteins 0.000 description 2
- 101000830565 Homo sapiens Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 206010065973 Iron Overload Diseases 0.000 description 2
- 206010023126 Jaundice Diseases 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 208000005230 Leg Ulcer Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 2
- 108010015920 Type I Activin Receptors Proteins 0.000 description 2
- 102000002138 Type I Activin Receptors Human genes 0.000 description 2
- 102000000523 Type II Activin Receptors Human genes 0.000 description 2
- 108010041546 Type II Activin Receptors Proteins 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 108010057453 activin receptor type II-B Proteins 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000022809 beta-thalassemia intermedia Diseases 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 231100000001 growth retardation Toxicity 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 230000011132 hemopoiesis Effects 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 description 2
- 208000020451 hereditary persistence of fetal hemoglobin Diseases 0.000 description 2
- 102000047803 human BIRC5 Human genes 0.000 description 2
- 102000045341 human CCL5 Human genes 0.000 description 2
- 102000049765 human CDKN1A Human genes 0.000 description 2
- 102000046438 human CXCL10 Human genes 0.000 description 2
- 102000056732 human GATA2 Human genes 0.000 description 2
- 102000044241 human GYPA Human genes 0.000 description 2
- 102000043559 human ICAM1 Human genes 0.000 description 2
- 102000052620 human IL10 Human genes 0.000 description 2
- 102000052611 human IL6 Human genes 0.000 description 2
- 102000057097 human MIF Human genes 0.000 description 2
- 102000046909 human PON2 Human genes 0.000 description 2
- 102000044949 human TNFSF10 Human genes 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 108010019691 inhibin beta A subunit Proteins 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 108091008104 nucleic acid aptamers Proteins 0.000 description 2
- 125000001151 peptidyl group Chemical group 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 208000002815 pulmonary hypertension Diseases 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010911 splenectomy Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-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
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 102100034134 Activin receptor type-1B Human genes 0.000 description 1
- 102100034135 Activin receptor type-1C Human genes 0.000 description 1
- 101710173005 Activin receptor type-1C Proteins 0.000 description 1
- 102220556625 Acyl-coenzyme A thioesterase 11_K55A_mutation Human genes 0.000 description 1
- 206010001367 Adrenal insufficiency Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 102100027453 Bcl2-associated agonist of cell death Human genes 0.000 description 1
- 101710081085 Bcl2-associated agonist of cell death Proteins 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 101000937267 Bos taurus Activin receptor type-2B Proteins 0.000 description 1
- 108010008978 Chemokine CXCL10 Proteins 0.000 description 1
- 102220578642 Chorion-specific transcription factor GCMb_K74M_mutation Human genes 0.000 description 1
- 108010028773 Complement C5 Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
- 108010016777 Cyclin-Dependent Kinase Inhibitor p27 Proteins 0.000 description 1
- 102000000577 Cyclin-Dependent Kinase Inhibitor p27 Human genes 0.000 description 1
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 1
- 101150082208 DIABLO gene Proteins 0.000 description 1
- 102100037024 E3 ubiquitin-protein ligase XIAP Human genes 0.000 description 1
- 102220575187 Egl nine homolog 1_F82A_mutation Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 101710100588 Erythroid transcription factor Proteins 0.000 description 1
- TZXKOCQBRNJULO-UHFFFAOYSA-N Ferriprox Chemical compound CC1=C(O)C(=O)C=CN1C TZXKOCQBRNJULO-UHFFFAOYSA-N 0.000 description 1
- 206010016880 Folate deficiency Diseases 0.000 description 1
- 101710082961 GATA-binding factor 2 Proteins 0.000 description 1
- 108010028165 GATA1 Transcription Factor Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000007366 Genu Valgum Diseases 0.000 description 1
- 102100033299 Glia-derived nexin Human genes 0.000 description 1
- 108091005250 Glycophorins Proteins 0.000 description 1
- 101710163784 Growth-regulated alpha protein Proteins 0.000 description 1
- 108010045100 HSP27 Heat-Shock Proteins Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102100039165 Heat shock protein beta-1 Human genes 0.000 description 1
- 108091005880 Hemoglobin F Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 description 1
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 1
- 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 description 1
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 1
- 101000893545 Homo sapiens Growth/differentiation factor 11 Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 102000039989 IL-17 family Human genes 0.000 description 1
- 108091069193 IL-17 family Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 206010062061 Knee deformity Diseases 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 102100037791 Macrophage migration inhibitory factor Human genes 0.000 description 1
- 101710119980 Macrophage migration inhibitory factor Proteins 0.000 description 1
- 108010036176 Melitten Proteins 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 206010027540 Microcytosis Diseases 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 206010049088 Osteopenia Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102220496976 Platelet-activating factor acetylhydrolase 2, cytoplasmic_L79A_mutation Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102220542870 Presenilins-associated rhomboid-like protein, mitochondrial_L79E_mutation Human genes 0.000 description 1
- 102220495689 Putative uncharacterized protein FLJ43944_R40A_mutation Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010005113 Serpin E2 Proteins 0.000 description 1
- 102000005821 Serpin E2 Human genes 0.000 description 1
- 102000043168 TGF-beta family Human genes 0.000 description 1
- 108091085018 TGF-beta family Proteins 0.000 description 1
- 108010000449 TNF-Related Apoptosis-Inducing Ligand Receptors Proteins 0.000 description 1
- 206010043391 Thalassaemia beta Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 102220610602 Vasoactive intestinal polypeptide receptor 1_R64E_mutation Human genes 0.000 description 1
- 102220610616 Vasoactive intestinal polypeptide receptor 1_R64K_mutation Human genes 0.000 description 1
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 1
- 208000022440 X-linked sideroblastic anemia 1 Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000017515 adrenocortical insufficiency Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000006288 alpha thalassemia Diseases 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003173 antianemic agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000018678 bone mineralization Effects 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960001489 deferasirox Drugs 0.000 description 1
- FMSOAWSKCWYLBB-VBGLAJCLSA-N deferasirox Chemical compound C1=CC(C(=O)O)=CC=C1N(N\C(N\1)=C\2C(C=CC=C/2)=O)C/1=C\1C(=O)C=CC=C/1 FMSOAWSKCWYLBB-VBGLAJCLSA-N 0.000 description 1
- 229960003266 deferiprone Drugs 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 210000000267 erythroid cell Anatomy 0.000 description 1
- 229940125367 erythropoiesis stimulating agent Drugs 0.000 description 1
- 210000002375 erythropoietic cell Anatomy 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
- 238000002474 experimental method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000046768 human CCL2 Human genes 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000006278 hypochromic anemia Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000007898 magnetic cell sorting Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- VDXZNPDIRNWWCW-UHFFFAOYSA-N melitten Chemical compound NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000008383 multiple organ dysfunction Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220288227 rs141863326 Human genes 0.000 description 1
- 102200145357 rs1555341957 Human genes 0.000 description 1
- 102200044417 rs28931612 Human genes 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 201000005665 thrombophilia Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/18—Erythrocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0641—Erythrocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/4833—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
-
- 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
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Analytical Chemistry (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Physics & Mathematics (AREA)
- Virology (AREA)
- Pathology (AREA)
- Endocrinology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562164367P | 2015-05-20 | 2015-05-20 | |
| US62/164,367 | 2015-05-20 | ||
| US201662320032P | 2016-04-08 | 2016-04-08 | |
| US62/320,032 | 2016-04-08 | ||
| PCT/US2016/033187 WO2016187378A1 (en) | 2015-05-20 | 2016-05-19 | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2986432A1 true CA2986432A1 (en) | 2016-11-24 |
Family
ID=57320751
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2986432A Pending CA2986432A1 (en) | 2015-05-20 | 2016-05-19 | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US10548976B2 (enExample) |
| EP (2) | EP4190805A3 (enExample) |
| JP (2) | JP2018522579A (enExample) |
| CN (1) | CN108350057A (enExample) |
| CA (1) | CA2986432A1 (enExample) |
| HK (1) | HK1252174A1 (enExample) |
| MA (1) | MA42160A (enExample) |
| WO (1) | WO2016187378A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2890217C (en) | 2012-11-02 | 2021-07-20 | Yifu FANG | Activin-actrii antagonists and uses for treating bone and other disorders |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| LT3227675T (lt) | 2014-12-03 | 2023-06-12 | Celgene Corporation | Aktivino actrii antagonistai ir naudojimas mielodisplastiniam sindromui gydyti |
| EP4190805A3 (en) | 2015-05-20 | 2023-08-16 | Celgene Corporation | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
| CN110461349B (zh) | 2016-11-10 | 2024-08-13 | 科乐斯疗法公司 | 激活素受体iia型变体及其使用方法 |
| CN110099995A (zh) * | 2017-01-06 | 2019-08-06 | 奥林巴斯株式会社 | 细胞观察系统 |
| EP3706777B1 (en) | 2017-11-09 | 2024-05-22 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| CA3087008A1 (en) | 2018-01-12 | 2019-07-18 | Keros Therapeutics, Inc. | Activin receptor type iib variants and methods of use thereof |
| JP7405772B2 (ja) | 2018-05-09 | 2023-12-26 | 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ｉｉａ型受容体変異体および同変異体を含む医薬組成物 |
| JP7388679B2 (ja) * | 2019-05-28 | 2023-11-29 | 学校法人 東洋大学 | 熱中症マーカー及びその利用 |
| IL296394A (en) * | 2020-03-20 | 2022-11-01 | Keros Therapeutics Inc | Type ii activin receptor chimeras and methods of using them |
| EP4121088A4 (en) | 2020-03-20 | 2024-07-03 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| US20230174620A1 (en) * | 2020-04-28 | 2023-06-08 | Acceleron Pharma Inc. | Actrii proteins and use in treating post-capillary pulmonary hypertension |
| BR112022025644A2 (pt) * | 2020-06-23 | 2023-03-07 | Acceleron Pharma Inc | Proteínas actrii para tratamento de hipertensão arterial pulmonar (pah) |
| US12186370B1 (en) | 2020-11-05 | 2025-01-07 | Celgene Corporation | ACTRIIB ligand trap compositions and uses thereof |
| WO2022098877A1 (en) * | 2020-11-06 | 2022-05-12 | Acceleron Pharma Inc. | Formulations comprising actrii polypeptide variants |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE452181T1 (de) | 1999-02-04 | 2010-01-15 | Pluristem Ltd | Verfahren und vorrichtung zur haltung und expansion von hematopoietischen stammzellen und/oder vorläuferzellen |
| EP2141243A3 (en) | 2000-10-16 | 2010-01-27 | Brystol-Myers Squibb Company | Protein scaffolds for antibody mimics and other binding proteins |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| DE60236861D1 (de) | 2001-04-26 | 2010-08-12 | Amgen Mountain View Inc | Kombinatorische bibliotheken von monomerdomänen |
| DK2332977T3 (en) | 2004-07-23 | 2016-02-29 | Acceleron Pharma Inc | ActRII receptor polypeptides |
| AU2005307789A1 (en) | 2004-11-16 | 2006-05-26 | Avidia Research Institute | Protein scaffolds and uses thereof |
| CA3045808C (en) | 2005-11-23 | 2022-08-16 | Acceleron Pharma, Inc. | Activin-actriia antagonists and uses for promoting bone growth |
| MX373050B (es) | 2006-12-18 | 2020-05-21 | Acceleron Pharma Inc | Antagonistas de activina-actrii y usos para incrementar los niveles de globulos rojos. |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| RU2473362C2 (ru) | 2007-02-01 | 2013-01-27 | Акселерон Фарма Инк. | АНТАГОНИСТЫ АКТИВИНА-ActRIIa-Fc И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ ИЛИ ПРОФИЛАКТИКИ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ |
| TW201907946A (zh) | 2007-02-02 | 2019-03-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 |
| WO2008100384A2 (en) | 2007-02-09 | 2008-08-21 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for promoting bone growth in cancer patients |
| CN101861161B (zh) | 2007-09-18 | 2017-04-19 | 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 |
| WO2009158025A2 (en) | 2008-06-26 | 2009-12-30 | Acceleron Pharma Inc. | Methods for dosing an actriib antagonist and monitoring of treated patients |
| TW201919685A (zh) * | 2008-08-14 | 2019-06-01 | 美商艾瑟勒朗法瑪公司 | 使用ｇｄｆ阱以增加紅血球水平 |
| 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 |
| CA2749544A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| CA2764890A1 (en) | 2009-06-08 | 2010-12-16 | Acceleron Pharma Inc. | Methods for increasing thermogenic adipocytes |
| CN104805105A (zh) | 2009-06-12 | 2015-07-29 | 阿塞勒隆制药公司 | 截短的actriib-fc融合蛋白 |
| RU2642302C1 (ru) | 2009-08-13 | 2018-01-24 | Акселерон Фарма Инк. | Комбинированное применение ловушек gdf и активаторов рецепторов эритропоэтина для повышения содержания эритроцитов |
| CA2773494A1 (en) | 2009-09-09 | 2011-03-17 | Acceleron Pharma Inc. | Actriib antagonists and dosing and uses thereof |
| ES2869864T3 (es) | 2009-11-03 | 2021-10-26 | Acceleron Pharma Inc | Procedimientos para el tratamiento de la enfermedad del hígado graso |
| 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 |
| EA202090053A3 (ru) | 2011-10-17 | 2020-06-30 | Акселерон Фарма, Инк. | Способы и композиции для лечения неэффективного эритропоэза |
| US20150276766A1 (en) | 2012-10-24 | 2015-10-01 | Celgene Corporation | Biomarker for use in treating anemia |
| US20150266950A1 (en) | 2012-10-24 | 2015-09-24 | Celgene Corporation | Methods for treating anemia |
| CA2890217C (en) | 2012-11-02 | 2021-07-20 | Yifu FANG | Activin-actrii antagonists and uses for treating bone and other disorders |
| AP2016009549A0 (en) | 2014-04-18 | 2016-11-30 | Acceleron Pharma Inc | Methods for increasing red blood cell levels and treating sickle-cell disease |
| AP2017009674A0 (en) | 2014-06-13 | 2017-01-31 | 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 |
| MA41119A (fr) | 2014-12-03 | 2017-10-10 | Acceleron Pharma Inc | Méthodes de traitement de syndromes myélodysplasiques et d'anémie sidéroblastique |
| LT3227675T (lt) | 2014-12-03 | 2023-06-12 | Celgene Corporation | Aktivino actrii antagonistai ir naudojimas mielodisplastiniam sindromui gydyti |
| JP6976859B2 (ja) | 2015-05-13 | 2021-12-08 | セルジーン コーポレイション | ＡｃｔＲＩＩリガンドトラップを用いたβ−サラセミアの治療 |
| EP4190805A3 (en) | 2015-05-20 | 2023-08-16 | Celgene Corporation | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
| EP3380121B1 (en) | 2015-11-23 | 2023-12-20 | Acceleron Pharma Inc. | Actrii antagonist for use in treating eye disorders |
| AU2017296040C1 (en) | 2016-07-15 | 2023-06-22 | Acceleron Pharma Inc. | Compositions and methods for treating pulmonary hypertension |
| CA3031909A1 (en) | 2016-07-27 | 2018-02-01 | Acceleron Pharma Inc. | Methods and compositions for treating myelofibrosis |
| US20200101134A1 (en) | 2017-06-14 | 2020-04-02 | Celgene Corporation | Methods for treating myeloproliferative neoplasm-associated myelofibrosis and anemia |
-
2016
- 2016-05-19 EP EP22201847.5A patent/EP4190805A3/en not_active Withdrawn
- 2016-05-19 EP EP16797267.8A patent/EP3298034A4/en not_active Withdrawn
- 2016-05-19 CA CA2986432A patent/CA2986432A1/en active Pending
- 2016-05-19 HK HK18111575.0A patent/HK1252174A1/zh unknown
- 2016-05-19 JP JP2018512825A patent/JP2018522579A/ja active Pending
- 2016-05-19 US US15/574,897 patent/US10548976B2/en not_active Expired - Fee Related
- 2016-05-19 MA MA042160A patent/MA42160A/fr unknown
- 2016-05-19 CN CN201680042691.9A patent/CN108350057A/zh active Pending
- 2016-05-19 WO PCT/US2016/033187 patent/WO2016187378A1/en not_active Ceased
-
2019
- 2019-12-11 US US16/711,039 patent/US20200101157A1/en not_active Abandoned
-
2021
- 2021-09-29 JP JP2021158571A patent/JP2022023072A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HK1252174A1 (zh) | 2019-05-17 |
| EP3298034A1 (en) | 2018-03-28 |
| EP4190805A3 (en) | 2023-08-16 |
| EP3298034A4 (en) | 2019-02-13 |
| US20200101157A1 (en) | 2020-04-02 |
| JP2018522579A (ja) | 2018-08-16 |
| US20180161426A1 (en) | 2018-06-14 |
| CN108350057A (zh) | 2018-07-31 |
| JP2022023072A (ja) | 2022-02-07 |
| US10548976B2 (en) | 2020-02-04 |
| WO2016187378A1 (en) | 2016-11-24 |
| EP4190805A2 (en) | 2023-06-07 |
| MA42160A (fr) | 2018-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20200101157A1 (en) | Vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps | |
| JP6501362B2 (ja) | エリスロフェロンおよびｅｒｆｅポリペプチドならびに鉄代謝を調節する方法 | |
| Garbers et al. | Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding | |
| Zhou et al. | A novel osteoblast-derived C-type lectin that inhibits osteoclast formation | |
| Ohnuma et al. | Regulation of pulmonary graft-versus-host disease by IL-26+ CD26+ CD4 T lymphocytes | |
| Dingenouts et al. | Mononuclear cells and vascular repair in HHT | |
| MXPA03006100A (es) | Metodos para tratar enfermedades auto inmunes en un sujeto y examenes de diagnostico en tubo de ensayo. | |
| Yasuoka et al. | The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration | |
| US20040072259A1 (en) | Methods and products for manipulating hematopoietic stem cells | |
| Dobashi et al. | Growth hormone restores glucocorticoid‐induced T cell suppression | |
| EP1517703B1 (en) | Placental growth factor as a target for the treatment of osteoporosis | |
| JP2023526590A (ja) | ＡｃｔＲＩＩＢリガンドトラップ及びｍＴＯＲ阻害剤を使用して貧血を治療するための方法及び組成物 | |
| Chakrabarti et al. | Control of islet intercellular adhesion molecule-1 expression by interferon-α and hypoxia | |
| US20170166648A1 (en) | Inhibitors of the cd95 signaling pathway for treatment of mds | |
| US20110039791A1 (en) | Acetylcholinesterase (ache)-derived peptide as an inducer of granulocytopoiesis, uses and methods thereof | |
| Socie | Recent advances in paroxysmal nocturnal hemoglobinuria: from the biology to the clinic | |
| Su | Role of impaired lipid metabolism and immune dysregulation in the pathogenesis of cardiovascular disease | |
| JP2025519561A (ja) | Ｇｐｃｒ阻害剤及びその使用 | |
| Barnes | C-mpl expression in osteoclast progenitors: a novel role for Thrombopoietin in regulating osteoclast development | |
| WO2002044345A1 (en) | Methods and products for manipulating hematopoietic stem cells | |
| WO2019099615A1 (en) | Use of copeptin to modulate the immune response and hematopoiesis, and stimulate bone growth | |
| Menon | ROLES FOR AN EPO-RECEPTOR PY343-STAT5 SIGNALING AXIS IN STRESS ERYTHROPOIESIS | |
| Hatano et al. | Regulation of Pulmonary Graft-versus-Host Disease by IL-26+ CD26+ CD4 T Lymphocytes | |
| Engel | Caveolin‐1 and CD40L‐CD40‐TRAF interactions in vascular and metabolic disease | |
| Bambara et al. | Soluble TNF-Like Cytokine (TL1A) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210510 |
|
| EEER | Examination request |
Effective date: 20210510 |
|
| EEER | Examination request |
Effective date: 20210510 |
|
| EEER | Examination request |
Effective date: 20210510 |
|
| EEER | Examination request |
Effective date: 20210510 |
|
| EEER | Examination request |
Effective date: 20210510 |