JP2016508504A5 - - Google Patents

Info

Publication number

JP2016508504A5

JP2016508504A5 JP2015556210A JP2015556210A JP2016508504A5 JP 2016508504 A5 JP2016508504 A5 JP 2016508504A5 JP 2015556210 A JP2015556210 A JP 2015556210A JP 2015556210 A JP2015556210 A JP 2015556210A JP 2016508504 A5 JP2016508504 A5 JP 2016508504A5

Authority

JP

Japan

Prior art keywords

activin

residue

subject

pharmaceutical composition

seq

Prior art date

2014-02-03

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

• Espacenet
• Global Dossier
• Discuss

• 108090000765 processed proteins & peptides Proteins 0.000 claims description 66
• 238000000034 method Methods 0.000 claims description 65
• 229920001184 polypeptide Polymers 0.000 claims description 65
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 65
• 108010023082 activin A Proteins 0.000 claims description 61
• 150000001875 compounds Chemical class 0.000 claims description 61
• 239000000090 biomarker Substances 0.000 claims description 27
• 108010059616 Activins Proteins 0.000 claims description 17
• 239000000488 activin Substances 0.000 claims description 16
• 102100039939 Growth/differentiation factor 8 Human genes 0.000 claims description 14
• 108010056852 Myostatin Proteins 0.000 claims description 14
• 206010033128 Ovarian cancer Diseases 0.000 claims description 14
• 101710194452 Growth/differentiation factor 11 Proteins 0.000 claims description 13
• 102100040898 Growth/differentiation factor 11 Human genes 0.000 claims description 13
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 13
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 13
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 13
• 230000035772 mutation Effects 0.000 claims description 12
• 102100026818 Inhibin beta E chain Human genes 0.000 claims description 11
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 10
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 10
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 10
• 229960004117 capecitabine Drugs 0.000 claims description 10
• 229960004679 doxorubicin Drugs 0.000 claims description 6
• -1 doxorubicin lipid Chemical class 0.000 claims description 6
• AOJJSUZBOXZQNB-TZSSRYMLSA-N doxorubicine Natural products O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 6
• 102000005962 receptors Human genes 0.000 claims description 6
• 230000000973 chemotherapeutic effect Effects 0.000 claims description 5
• 230000001517 counterregulatory effect Effects 0.000 claims description 4
• 108090000623 proteins and genes Proteins 0.000 claims description 4
• 102220535144 Inhibin beta A chain_G280E_mutation Human genes 0.000 claims description 3
• 102200020100 rs121908514 Human genes 0.000 claims description 3
• 102200063532 rs34377097 Human genes 0.000 claims description 3
• 201000004462 Leydig Cell Tumor Diseases 0.000 claims description 2
• 210000002503 granulosa cell Anatomy 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 23
• 239000000427 antigen Substances 0.000 claims 4
• 102000036639 antigens Human genes 0.000 claims 4
• 108091007433 antigens Proteins 0.000 claims 4
• 239000012634 fragment Substances 0.000 claims 4
• 108020001507 fusion proteins Proteins 0.000 claims 2
• 102000037865 fusion proteins Human genes 0.000 claims 2
• 208000002669 Sex Cord-Gonadal Stromal Tumors Diseases 0.000 claims 1
• 239000000203 mixture Substances 0.000 claims 1
• 208000016632 ovarian clear cell cancer Diseases 0.000 claims 1
• 201000003707 ovarian clear cell carcinoma Diseases 0.000 claims 1
• 238000006467 substitution reaction Methods 0.000 description 44
• 235000001014 amino acid Nutrition 0.000 description 41
• 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 28
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 26
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 22
• 229940024606 amino acid Drugs 0.000 description 21
• 150000001413 amino acids Chemical class 0.000 description 21
• 125000003275 alpha amino acid group Chemical group 0.000 description 20
• CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 20
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 16
• 102000040430 polynucleotide Human genes 0.000 description 16
• 108091033319 polynucleotide Proteins 0.000 description 16
• 239000002157 polynucleotide Substances 0.000 description 16
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 14
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 12
• 239000000523 sample Substances 0.000 description 12
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 10
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 10
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 10
• 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 8
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 8
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 8
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 6
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 6
• 239000013642 negative control Substances 0.000 description 6
• 239000013641 positive control Substances 0.000 description 6
• 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 4
• 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 4
• 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 4
• 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 4
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
• 230000000295 complement effect Effects 0.000 description 4
• 230000037430 deletion Effects 0.000 description 4
• 238000012217 deletion Methods 0.000 description 4
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 4
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
• ZCZNGRXPMRPERV-UHFFFAOYSA-N 4,4'-diarsene-1,2-diylbis(2-aminophenol) Chemical compound C1=C(O)C(N)=CC([As]=[As]C=2C=C(N)C(O)=CC=2)=C1 ZCZNGRXPMRPERV-UHFFFAOYSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 102000025171 antigen binding proteins Human genes 0.000 description 2
• 108091000831 antigen binding proteins Proteins 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• LBELXQDPBJDSGT-NBYYMMLRSA-N n,n-diethyl-4-[(e)-2-quinolin-4-ylethenyl]aniline;hydrochloride Chemical compound Cl.C1=CC(N(CC)CC)=CC=C1\C=C\C1=CC=NC2=CC=CC=C12 LBELXQDPBJDSGT-NBYYMMLRSA-N 0.000 description 2
• OOFQRYZVURFSOS-UHFFFAOYSA-N sodium;4-[2-(7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)ethoxy]-4-oxobutanoic acid Chemical compound [Na+].OC(=O)CCC(=O)OCCN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O OOFQRYZVURFSOS-UHFFFAOYSA-N 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 208000025189 neoplasm of testis Diseases 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1