JP2020500511A5 - - Google Patents
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- JP2020500511A5 JP2020500511A5 JP2019526306A JP2019526306A JP2020500511A5 JP 2020500511 A5 JP2020500511 A5 JP 2020500511A5 JP 2019526306 A JP2019526306 A JP 2019526306A JP 2019526306 A JP2019526306 A JP 2019526306A JP 2020500511 A5 JP2020500511 A5 JP 2020500511A5
- Authority
- JP
- Japan
- Prior art keywords
- residue
- tgf
- monomer
- amino acid
- substitution
- 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.)
- Granted
Links
- 239000000178 monomer Substances 0.000 claims description 80
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 58
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 58
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 58
- 238000006467 substitution reaction Methods 0.000 claims description 54
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 125000000539 amino acid group Chemical group 0.000 claims description 37
- 108020001507 fusion proteins Proteins 0.000 claims description 30
- 102000037865 fusion proteins Human genes 0.000 claims description 30
- 230000011664 signaling Effects 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- 239000004475 Arginine Substances 0.000 claims description 22
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 22
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 22
- 239000004472 Lysine Substances 0.000 claims description 21
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 21
- 235000004279 alanine Nutrition 0.000 claims description 20
- 230000002159 abnormal effect Effects 0.000 claims description 19
- 235000001014 amino acid Nutrition 0.000 claims description 17
- 150000001294 alanine derivatives Chemical class 0.000 claims description 14
- 235000018102 proteins Nutrition 0.000 claims description 13
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 13
- 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 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 12
- 229960000310 isoleucine Drugs 0.000 claims description 12
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 12
- 101500025624 Homo sapiens Transforming growth factor beta-2 Proteins 0.000 claims description 11
- 210000004027 cell Anatomy 0.000 claims description 10
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 9
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 9
- 239000004474 valine Substances 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 101500025614 Homo sapiens Transforming growth factor beta-1 Proteins 0.000 claims description 6
- 101500026551 Homo sapiens Transforming growth factor beta-3 Proteins 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
- 150000002614 leucines Chemical class 0.000 claims description 6
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 5
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 5
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 5
- 235000013922 glutamic acid Nutrition 0.000 claims description 5
- 239000004220 glutamic acid Substances 0.000 claims description 5
- 102000009027 Albumins Human genes 0.000 claims description 4
- 108010088751 Albumins Proteins 0.000 claims description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004473 Threonine Substances 0.000 claims description 4
- 235000009582 asparagine Nutrition 0.000 claims description 4
- 229960001230 asparagine Drugs 0.000 claims description 4
- 235000003704 aspartic acid Nutrition 0.000 claims description 4
- 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 4
- 208000030533 eye disease Diseases 0.000 claims description 4
- 208000037176 hereditary disorder of connective tissue Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 229930195712 glutamate Natural products 0.000 claims description 3
- 150000002519 isoleucine derivatives Chemical class 0.000 claims description 3
- 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 3
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 2
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 claims description 2
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 235000018417 cysteine Nutrition 0.000 claims description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
- 238000012217 deletion Methods 0.000 claims description 2
- 230000037430 deletion Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000007850 fluorescent dye Substances 0.000 claims description 2
- 102000034287 fluorescent proteins Human genes 0.000 claims description 2
- 108091006047 fluorescent proteins Proteins 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 239000000833 heterodimer Substances 0.000 claims description 2
- 239000012216 imaging agent Substances 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 230000001594 aberrant effect Effects 0.000 claims 3
- 229940024606 amino acid Drugs 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021214183A JP7623273B2 (ja) | 2016-11-18 | 2021-12-28 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
| JP2023160199A JP2023164748A (ja) | 2016-11-18 | 2023-09-25 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662423920P | 2016-11-18 | 2016-11-18 | |
| US62/423,920 | 2016-11-18 | ||
| PCT/US2017/062233 WO2018094173A1 (en) | 2016-11-18 | 2017-11-17 | Engineered tgf-beta monomers and their use for inhibiting tgf-beta signaling |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021214183A Division JP7623273B2 (ja) | 2016-11-18 | 2021-12-28 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020500511A JP2020500511A (ja) | 2020-01-16 |
| JP2020500511A5 true JP2020500511A5 (https=) | 2020-11-19 |
| JP7079779B2 JP7079779B2 (ja) | 2022-06-02 |
Family
ID=62146703
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019526306A Active JP7079779B2 (ja) | 2016-11-18 | 2017-11-17 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
| JP2021214183A Active JP7623273B2 (ja) | 2016-11-18 | 2021-12-28 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
| JP2023160199A Withdrawn JP2023164748A (ja) | 2016-11-18 | 2023-09-25 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021214183A Active JP7623273B2 (ja) | 2016-11-18 | 2021-12-28 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
| JP2023160199A Withdrawn JP2023164748A (ja) | 2016-11-18 | 2023-09-25 | 操作されたｔｇｆベータ単量体およびｔｇｆベータシグナル伝達のためのそれらの使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US11091523B2 (https=) |
| EP (1) | EP3541409B1 (https=) |
| JP (3) | JP7079779B2 (https=) |
| ES (1) | ES3011833T3 (https=) |
| PT (1) | PT3541409T (https=) |
| WO (1) | WO2018094173A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018094173A1 (en) * | 2016-11-18 | 2018-05-24 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Engineered tgf-beta monomers and their use for inhibiting tgf-beta signaling |
| US20220409684A1 (en) * | 2019-11-18 | 2022-12-29 | The Brigham And Women's Hospital, Inc. | Codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus type 1 virus and methods of use |
| WO2022047220A1 (en) * | 2020-08-27 | 2022-03-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Oncolytic viruses encoding recombinant tranforming growth factor (tgf)-beta monomers and uses thereof |
| WO2022139493A1 (ko) * | 2020-12-23 | 2022-06-30 | 한국과학기술연구원 | TGF-β 신호전달을 억제할 수 있는 신규한 펩타이드 및 이의 용도 |
| CN118103390A (zh) * | 2021-10-11 | 2024-05-28 | 联邦高等教育系统匹兹堡大学 | 工程化TGF-β单体及其使用方法 |
| JP2024096518A (ja) * | 2023-01-03 | 2024-07-16 | エフビーデー バイオロジクス リミテッド | 操作されたｔｇｆｂｒｉｉバリアント及びその使用方法 |
| JP2026503849A (ja) * | 2023-01-30 | 2026-01-30 | シアトル チルドレンズ ホスピタル ディー／ビー／エイ シアトル チルドレンズ リサーチ インスティテュート | 免疫細胞の機能を増強するための誘導型サイトカイン導入遺伝子 |
| KR20260019369A (ko) | 2023-05-31 | 2026-02-10 | 에프비디 바이올로직스 리미티드 | Cd47/pd-l1-표적화 단백질 복합체 및 그의 사용 방법 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
| EP1668133A4 (en) | 2003-09-05 | 2007-08-29 | Ca Nat Research Council | BISPIRALEE HYBRID PROTEIN WITH DOMAINS OF CELL RECEPTORS |
| WO2011094749A2 (en) | 2010-02-01 | 2011-08-04 | Board Of Regents, The University Of Texas System | Small molecule inhibitors that block assembly of the tgf-beta signaling complex |
| CU24181B1 (es) | 2012-11-09 | 2016-04-25 | Ct De Inmunología Molecular | POLIPÉPTIDOS DERIVADOS DEL TGFß |
| WO2018094173A1 (en) | 2016-11-18 | 2018-05-24 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Engineered tgf-beta monomers and their use for inhibiting tgf-beta signaling |
-
2017
- 2017-11-17 WO PCT/US2017/062233 patent/WO2018094173A1/en not_active Ceased
- 2017-11-17 EP EP17871472.1A patent/EP3541409B1/en active Active
- 2017-11-17 ES ES17871472T patent/ES3011833T3/es active Active
- 2017-11-17 US US16/461,747 patent/US11091523B2/en active Active
- 2017-11-17 JP JP2019526306A patent/JP7079779B2/ja active Active
- 2017-11-17 PT PT178714721T patent/PT3541409T/pt unknown
-
2021
- 2021-07-07 US US17/369,736 patent/US12428460B2/en active Active
- 2021-12-28 JP JP2021214183A patent/JP7623273B2/ja active Active
-
2023
- 2023-09-25 JP JP2023160199A patent/JP2023164748A/ja not_active Withdrawn
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