JP2017522877A5 - - Google Patents

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Publication number

JP2017522877A5

JP2017522877A5 JP2017503089A JP2017503089A JP2017522877A5 JP 2017522877 A5 JP2017522877 A5 JP 2017522877A5 JP 2017503089 A JP2017503089 A JP 2017503089A JP 2017503089 A JP2017503089 A JP 2017503089A JP 2017522877 A5 JP2017522877 A5 JP 2017522877A5

Authority

JP

Japan

Prior art keywords

amino acid

fhbp

variant

substitution

acid substitution

Prior art date

2015-07-22

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

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• 150000001413 amino acids Chemical class 0.000 claims description 94
• 101710186862 Factor H binding protein Proteins 0.000 claims description 93
• 238000006467 substitution reaction Methods 0.000 claims description 84
• 235000001014 amino acid Nutrition 0.000 claims description 74
• 229940024606 amino acid Drugs 0.000 claims description 17
• 230000005875 antibody response Effects 0.000 claims description 11
• 230000002163 immunogen Effects 0.000 claims description 10
• 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 9
• 230000000844 anti-bacterial effect Effects 0.000 claims description 9
• 101000737574 Homo sapiens Complement factor H Proteins 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 7
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 7
• 102000045512 human CFH Human genes 0.000 claims description 7
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
• 239000004471 Glycine Substances 0.000 claims description 6
• 102000039446 nucleic acids Human genes 0.000 claims description 6
• 108020004707 nucleic acids Proteins 0.000 claims description 6
• 150000007523 nucleic acids Chemical class 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 238000000034 method Methods 0.000 claims description 5
• 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 5
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
• 241000588650 Neisseria meningitidis Species 0.000 claims description 4
• 239000013604 expression vector Substances 0.000 claims description 4
• 235000013922 glutamic acid Nutrition 0.000 claims description 4
• 239000004220 glutamic acid Substances 0.000 claims description 4
• 125000000291 glutamic acid group Chemical class N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 4
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 4
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 4
• 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 4
• 238000003259 recombinant expression Methods 0.000 claims description 4
• 102200128616 rs121908751 Human genes 0.000 claims description 4
• 102220466919 Runt-related transcription factor 1_R80A_mutation Human genes 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 239000004475 Arginine Substances 0.000 claims description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
• 239000004472 Lysine Substances 0.000 claims description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
• 102000018697 Membrane Proteins Human genes 0.000 claims description 2
• 108010052285 Membrane Proteins Proteins 0.000 claims description 2
• 241000588653 Neisseria Species 0.000 claims description 2
• 102220534532 Protein quaking_Q38K_mutation Human genes 0.000 claims description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 2
• 239000004473 Threonine Substances 0.000 claims description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
• ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical group O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
• 229960001230 asparagine Drugs 0.000 claims description 2
• 235000009582 asparagine Nutrition 0.000 claims description 2
• 235000003704 aspartic acid Nutrition 0.000 claims description 2
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
• 102220481542 eIF5-mimic protein 2_R41A_mutation Human genes 0.000 claims description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 2
• 125000000404 glutamine group Chemical class N[C@@H](CCC(N)=O)C(=O)* 0.000 claims description 2
• 150000002333 glycines Chemical class 0.000 claims description 2
• 238000000338 in vitro Methods 0.000 claims description 2
• 230000001939 inductive effect Effects 0.000 claims description 2
• 229960000310 isoleucine Drugs 0.000 claims description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 2
• 238000002360 preparation method Methods 0.000 claims description 2
• 102220279362 rs1554893806 Human genes 0.000 claims description 2
• 102220056952 rs730880947 Human genes 0.000 claims description 2
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims description 2
• 239000004474 valine Substances 0.000 claims description 2
• 125000002987 valine group Chemical class [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
• 230000005847 immunogenicity Effects 0.000 claims 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 description 3