AU2017268348A1 - T-cell modulatory multimeric polypeptides and methods of use thereof - Google Patents
T-cell modulatory multimeric polypeptides and methods of use thereof Download PDFInfo
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- AU2017268348A1 AU2017268348A1 AU2017268348A AU2017268348A AU2017268348A1 AU 2017268348 A1 AU2017268348 A1 AU 2017268348A1 AU 2017268348 A AU2017268348 A AU 2017268348A AU 2017268348 A AU2017268348 A AU 2017268348A AU 2017268348 A1 AU2017268348 A1 AU 2017268348A1
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- polypeptide
- amino acid
- variant
- substitution
- acid sequence
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- 229920001184 polypeptide Polymers 0.000 title claims abstract description 542
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 542
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 542
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 79
- 238000000034 method Methods 0.000 title claims abstract description 28
- 230000002519 immonomodulatory effect Effects 0.000 claims abstract description 120
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 25
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 25
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 25
- 210000004027 cell Anatomy 0.000 claims abstract description 19
- 230000000694 effects Effects 0.000 claims abstract description 9
- 150000001413 amino acids Chemical group 0.000 claims description 217
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 100
- 230000027455 binding Effects 0.000 claims description 95
- 235000001014 amino acid Nutrition 0.000 claims description 71
- 238000006467 substitution reaction Methods 0.000 claims description 54
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims description 49
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims description 48
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 44
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 40
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 40
- 229940024606 amino acid Drugs 0.000 claims description 32
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- 230000002829 reductive effect Effects 0.000 claims description 22
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- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 13
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- 108010061238 threonyl-glycine Proteins 0.000 claims 60
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- 108010076324 alanyl-glycyl-glycine Proteins 0.000 claims 35
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- ALNKNYKSZPSLBD-ZDLURKLDSA-N Cys-Thr-Gly Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ALNKNYKSZPSLBD-ZDLURKLDSA-N 0.000 claims 28
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- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 claims 24
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 claims 24
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- 108010079364 N-glycylalanine Proteins 0.000 claims 22
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- FKLSMYYLJHYPHH-UWVGGRQHSA-N Pro-Gly-Leu Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O FKLSMYYLJHYPHH-UWVGGRQHSA-N 0.000 claims 21
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 claims 21
- 102000002627 4-1BB Ligand Human genes 0.000 claims 20
- 108010082808 4-1BB Ligand Proteins 0.000 claims 20
- 108010025826 prolyl-leucyl-arginine Proteins 0.000 claims 20
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 claims 19
- SGYSTDWPNPKJPP-GUBZILKMSA-N Arg-Ala-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SGYSTDWPNPKJPP-GUBZILKMSA-N 0.000 claims 19
- SBVMXEZQJVUARN-XPUUQOCRSA-N Gly-Val-Ser Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O SBVMXEZQJVUARN-XPUUQOCRSA-N 0.000 claims 19
- UCOCBWDBHCUPQP-DCAQKATOSA-N Leu-Arg-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O UCOCBWDBHCUPQP-DCAQKATOSA-N 0.000 claims 19
- CSFVADKICPDRRF-KKUMJFAQSA-N Leu-His-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CN=CN1 CSFVADKICPDRRF-KKUMJFAQSA-N 0.000 claims 19
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 claims 19
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- KDBHVPXBQADZKY-GUBZILKMSA-N Pro-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KDBHVPXBQADZKY-GUBZILKMSA-N 0.000 claims 19
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- 108010067216 glycyl-glycyl-glycine Proteins 0.000 claims 19
- 108010089804 glycyl-threonine Proteins 0.000 claims 19
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- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 claims 17
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| US20230279075A1 (en) | 2023-09-07 |
| IL262403A (en) | 2018-12-31 |
| US20190106476A1 (en) | 2019-04-11 |
| BR112018073606A2 (pt) | 2019-02-26 |
| WO2017201210A1 (en) | 2017-11-23 |
| US11505591B2 (en) | 2022-11-22 |
| CA3019005A1 (en) | 2017-11-23 |
| EP3458096A1 (en) | 2019-03-27 |
| JP7071288B2 (ja) | 2022-05-18 |
| SG11201808552XA (en) | 2018-10-30 |
| KR20190019068A (ko) | 2019-02-26 |
| CN109475628A (zh) | 2019-03-15 |
| JP2019522465A (ja) | 2019-08-15 |
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