JP2010518079A5 - - Google Patents

Info

Publication number

JP2010518079A5

JP2010518079A5 JP2009549079A JP2009549079A JP2010518079A5 JP 2010518079 A5 JP2010518079 A5 JP 2010518079A5 JP 2009549079 A JP2009549079 A JP 2009549079A JP 2009549079 A JP2009549079 A JP 2009549079A JP 2010518079 A5 JP2010518079 A5 JP 2010518079A5

Authority

JP

Japan

Prior art keywords

actriia

fusion protein

pharmaceutical composition

amino acid

acid sequence

Prior art date

2008-02-01

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.)

Granted

Links

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• 102000037865 fusion proteins Human genes 0.000 claims description 128
• 108020001507 fusion proteins Proteins 0.000 claims description 128
• 239000008194 pharmaceutical composition Substances 0.000 claims description 68
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 64
• 150000001413 amino acids Chemical class 0.000 claims description 34
• 229920001184 polypeptide Polymers 0.000 claims description 31
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 31
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 31
• 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 28
• 239000005557 antagonist Substances 0.000 claims description 22
• 125000005629 sialic acid group Chemical group 0.000 claims description 20
• 239000000539 dimer Substances 0.000 claims description 16
• 210000002966 serum Anatomy 0.000 claims description 16
• 230000002265 prevention Effects 0.000 claims description 13
• 206010065687 Bone loss Diseases 0.000 claims description 12
• 206010028980 Neoplasm Diseases 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 208000034578 Multiple myelomas Diseases 0.000 claims description 10
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 10
• 208000006386 Bone Resorption Diseases 0.000 claims description 8
• 241000282412 Homo Species 0.000 claims description 8
• 230000008468 bone growth Effects 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 239000002250 absorbent Substances 0.000 claims description 6
• 239000000488 activin Substances 0.000 claims description 6
• 230000024279 bone resorption Effects 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 230000001737 promoting effect Effects 0.000 claims description 6
• 210000002027 skeletal muscle Anatomy 0.000 claims description 6
• 238000002560 therapeutic procedure Methods 0.000 claims description 6
• 102000005606 Activins Human genes 0.000 claims description 4
• 108010059616 Activins Proteins 0.000 claims description 4
• 229940122361 Bisphosphonate Drugs 0.000 claims description 4
• 102000008108 Osteoprotegerin Human genes 0.000 claims description 4
• 108010035042 Osteoprotegerin Proteins 0.000 claims description 4
• 102000014128 RANK Ligand Human genes 0.000 claims description 4
• 108010025832 RANK Ligand Proteins 0.000 claims description 4
• 125000000539 amino acid group Chemical group 0.000 claims description 4
• 150000004663 bisphosphonates Chemical class 0.000 claims description 4
• 210000004027 cell Anatomy 0.000 claims description 4
• 229940127089 cytotoxic agent Drugs 0.000 claims description 4
• 239000003446 ligand Substances 0.000 claims description 4
• 125000003473 lipid group Chemical group 0.000 claims description 4
• XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 claims description 4
• 230000011664 signaling Effects 0.000 claims description 4
• 239000002246 antineoplastic agent Substances 0.000 claims description 2
• 210000004899 c-terminal region Anatomy 0.000 claims description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 2
• 239000002254 cytotoxic agent Substances 0.000 claims description 2
• 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
• 235000004252 protein component Nutrition 0.000 claims description 2
• 238000001959 radiotherapy Methods 0.000 claims description 2
• 238000007920 subcutaneous administration Methods 0.000 claims description 2
• 239000000203 mixture Substances 0.000 claims 2
• 238000010521 absorption reaction Methods 0.000 claims 1
• 238000000034 method Methods 0.000 description 65
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 229920002684 Sepharose Polymers 0.000 description 2
• 230000018678 bone mineralization Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 238000001542 size-exclusion chromatography Methods 0.000 description 2
• 238000005277 cation exchange chromatography Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 238000011100 viral filtration Methods 0.000 description 1