JPWO2021119516A5 - - Google Patents
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- JPWO2021119516A5 JPWO2021119516A5 JP2022535520A JP2022535520A JPWO2021119516A5 JP WO2021119516 A5 JPWO2021119516 A5 JP WO2021119516A5 JP 2022535520 A JP2022535520 A JP 2022535520A JP 2022535520 A JP2022535520 A JP 2022535520A JP WO2021119516 A5 JPWO2021119516 A5 JP WO2021119516A5
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- 108090000765 processed proteins & peptides Proteins 0.000 claims 36
- 125000003275 alpha amino acid group Chemical group 0.000 claims 22
- 229920001184 polypeptide Polymers 0.000 claims 21
- 102000004196 processed proteins & peptides Human genes 0.000 claims 21
- 239000003814 drug Substances 0.000 claims 14
- 230000000975 bioactive effect Effects 0.000 claims 13
- 229940079593 drug Drugs 0.000 claims 13
- 230000005714 functional activity Effects 0.000 claims 8
- 230000000873 masking effect Effects 0.000 claims 8
- 108010002350 Interleukin-2 Proteins 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 108091005804 Peptidases Proteins 0.000 claims 4
- 239000004365 Protease Substances 0.000 claims 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 230000009977 dual effect Effects 0.000 claims 4
- 238000000034 method Methods 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 2
- 206010027476 Metastases Diseases 0.000 claims 2
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 230000009401 metastasis Effects 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
Claims (20)
1)組織または患部標的部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせる働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;または
1)二重機能性部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせ保持する働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;
D2は、配列番号182~192および199~215に記載のアミノ酸配列を有するポリペプチドの群から選択されるIL-15バリアントポリペプチドであり、
D1は、配列番号14、配列番号15、配列番号16、配列番号156、および配列番号166~168に記載の各アミノ酸配列からなる群から選択されるアミノ酸配列を有するFcドメインであり、
前記D3ドメインは、IL-15に対するコグネイト受容体/結合パートナー(またはそのバリアント)であり、配列番号4に記載のアミノ酸配列または任意のその機能性断片を含む、または、配列番号5に記載のアミノ酸配列を含む、
生理活性化ポリペプチド薬構築体。 A physiologically active polypeptide drug construct comprising, from the N-terminus to the C-terminus (D1-D2-D3),
1) a D1 domain (“D1”) that is a tissue or diseased area target portion; 2) a D2 domain (“D2”) that is a physiologically active portion; and 3) a D3 domain (“D3”) that is a shielding portion. wherein D1 serves to target the bioactive moiety to the desired treatment site; D3 is capable of masking the functional activity of D2 until activated at the desired treatment site; or
1) a D1 domain (“D1”) that is a dual functional moiety; 2) a D2 domain (“D2”) that is a physiologically active moiety; and 3) a D3 domain (“D3”) that is a shielding moiety. D1 serves to target and retain the bioactive moiety at the desired treatment site; D3 is capable of masking the functional activity of D2 until it is activated at the desired treatment site. ;
D2 is an IL-15 variant polypeptide selected from the group of polypeptides having the amino acid sequences set forth in SEQ ID NOs: 182-192 and 199-215;
D1 is an Fc domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 156, and each amino acid sequence set forth in SEQ ID NO: 166 to 168;
Said D3 domain is a cognate receptor/binding partner for IL-15 (or a variant thereof) and comprises the amino acid sequence set forth in SEQ ID NO: 4 or any functional fragment thereof, or the amino acid sequence set forth in SEQ ID NO: 5. containing an array,
Bioactivated polypeptide drug construct.
1)組織または患部標的部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせる働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;または
1)二重機能性部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせ保持する働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;
D2は、配列番号232~247に記載のアミノ酸配列を有するポリペプチドの群から選択されるIL-2バリアントポリペプチドであり、
D1は、配列番号14、配列番号15、配列番号16、配列番号156、および配列番号166~168に記載の各アミノ酸配列からなる群から選択されるアミノ酸配列を有するFcドメインであり、
前記D3ドメインは、IL-2に対するコグネイト受容体/結合パートナー(またはそのバリアント)であり、配列番号10および267~270に記載のアミノ酸配列を含む、
生理活性化ポリペプチド薬構築体。 A physiologically active polypeptide drug construct comprising, from the N-terminus to the C-terminus (D1-D2-D3),
1) a D1 domain (“D1”) that is a tissue or diseased area target portion; 2) a D2 domain (“D2”) that is a physiologically active portion; and 3) a D3 domain (“D3”) that is a shielding portion. wherein D1 serves to target the bioactive moiety to the desired treatment site; D3 is capable of masking the functional activity of D2 until activated at the desired treatment site; or
1) a D1 domain (“D1”) that is a dual functional moiety; 2) a D2 domain (“D2”) that is a physiologically active moiety; and 3) a D3 domain (“D3”) that is a shielding moiety. D1 serves to target and retain the bioactive moiety at the desired treatment site; D3 is capable of masking the functional activity of D2 until it is activated at the desired treatment site. ;
D2 is an IL-2 variant polypeptide selected from the group of polypeptides having the amino acid sequence set forth in SEQ ID NOs: 232-247;
D1 is an Fc domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 156, and each amino acid sequence set forth in SEQ ID NO: 166 to 168;
said D3 domain is a cognate receptor/binding partner for IL-2 (or a variant thereof) and comprises the amino acid sequence set forth in SEQ ID NO: 10 and 267-270;
Bioactivated polypeptide drug construct.
1)組織または患部標的部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせる働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;または1) a D1 domain (“D1”) that is a tissue or diseased area target portion; 2) a D2 domain (“D2”) that is a physiologically active portion; and 3) a D3 domain (“D3”) that is a shielding portion. wherein D1 serves to target the bioactive moiety to the desired treatment site; D3 is capable of masking the functional activity of D2 until activated at the desired treatment site; or
1)二重機能性部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせ保持する働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;1) a D1 domain (“D1”) that is a dual functional moiety; 2) a D2 domain (“D2”) that is a physiologically active moiety; and 3) a D3 domain (“D3”) that is a shielding moiety. D1 serves to target and retain the bioactive moiety at the desired treatment site; D3 is capable of masking the functional activity of D2 until it is activated at the desired treatment site. ;
D2は、配列番号182~192および199~215に記載のアミノ酸配列を有するポリペプチドの群から選択されるIL-15バリアントポリペプチドでありD2 is an IL-15 variant polypeptide selected from the group of polypeptides having the amino acid sequences set forth in SEQ ID NOs: 182-192 and 199-215.
D1は、配列番号195および196に記載の重鎖および軽鎖アミノ酸配列、配列番号197および198に記載の重鎖および軽鎖アミノ酸配列、配列番号275および276に記載の重鎖および軽鎖アミノ酸配列、または配列番号277および278に記載の重鎖および軽鎖アミノ酸配列を含む抗体から選択されるアンタゴニストヒト化PD-1抗体であり、D1 is the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 195 and 196, the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 197 and 198, and the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 275 and 276. , or an antagonist humanized PD-1 antibody selected from antibodies comprising the heavy chain and light chain amino acid sequences set forth in SEQ ID NOs: 277 and 278,
前記D3ドメインは、IL-15に対するコグネイト受容体/結合パートナー(またはそのバリアント)であり、配列番号4に記載のアミノ酸配列または任意のその機能性断片を含む、または、配列番号5に記載のアミノ酸配列を含む、Said D3 domain is a cognate receptor/binding partner for IL-15 (or a variant thereof) and comprises the amino acid sequence set forth in SEQ ID NO: 4 or any functional fragment thereof, or the amino acid sequence set forth in SEQ ID NO: 5. containing an array,
生理活性化ポリペプチド薬構築体。Bioactivated polypeptide drug construct.
1)組織または患部標的部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせる働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;または1) a D1 domain (“D1”) that is a tissue or diseased area target portion; 2) a D2 domain (“D2”) that is a physiologically active portion; and 3) a D3 domain (“D3”) that is a shielding portion. wherein D1 serves to target the bioactive moiety to the desired treatment site; D3 is capable of masking the functional activity of D2 until activated at the desired treatment site; or
1)二重機能性部分であるD1ドメイン(「D1」)と、2)生理活性化部分であるD2ドメイン(「D2」)と、3)遮蔽部分であるD3ドメイン(「D3」)と、を含み、D1は、前記生理活性化部分を目的の治療部位にターゲティングさせ保持する働きをし;D3は、目的の治療部位で活性化されるまでD2の機能活性を遮蔽することが可能であり;1) a D1 domain (“D1”) that is a dual functional moiety; 2) a D2 domain (“D2”) that is a physiologically active moiety; and 3) a D3 domain (“D3”) that is a shielding moiety. D1 serves to target and retain the bioactive moiety at the desired treatment site; D3 is capable of masking the functional activity of D2 until it is activated at the desired treatment site. ;
D2は、配列番号232~247に記載のアミノ酸配列を有するポリペプチドの群から選択されるIL-2バリアントポリペプチドであり、D2 is an IL-2 variant polypeptide selected from the group of polypeptides having the amino acid sequence set forth in SEQ ID NOs: 232-247;
D1は、配列番号195および196に記載の重鎖および軽鎖アミノ酸配列、配列番号197および198に記載の重鎖および軽鎖アミノ酸配列、配列番号275および276に記載の重鎖および軽鎖アミノ酸配列、または配列番号277および278に記載の重鎖および軽鎖アミノ酸配列を含む抗体から選択されるアンタゴニストヒト化PD-1抗体であり、D1 is the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 195 and 196, the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 197 and 198, and the heavy chain and light chain amino acid sequence set forth in SEQ ID NO: 275 and 276. , or an antagonist humanized PD-1 antibody selected from antibodies comprising the heavy chain and light chain amino acid sequences set forth in SEQ ID NOs: 277 and 278,
前記D3ドメインは、IL-2に対するコグネイト受容体/結合パートナー(またはそのバリアント)であり、配列番号10および267~270に記載のアミノ酸配列を含む、said D3 domain is a cognate receptor/binding partner for IL-2 (or a variant thereof) and comprises the amino acid sequence set forth in SEQ ID NO: 10 and 267-270;
生理活性化ポリペプチド薬構築体。Bioactivated polypeptide drug construct.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962947749P | 2019-12-13 | 2019-12-13 | |
US62/947,749 | 2019-12-13 | ||
PCT/US2020/064651 WO2021119516A1 (en) | 2019-12-13 | 2020-12-11 | Cytokine-based bioactivatable drugs and methods of uses thereof |
Publications (2)
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JP2023506454A JP2023506454A (en) | 2023-02-16 |
JPWO2021119516A5 true JPWO2021119516A5 (en) | 2023-12-19 |
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JP2022535520A Pending JP2023506454A (en) | 2019-12-13 | 2020-12-11 | Cytokine-based bioactivating agents and their uses |
Country Status (9)
Country | Link |
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US (1) | US20230093155A1 (en) |
EP (1) | EP4072593A4 (en) |
JP (1) | JP2023506454A (en) |
KR (1) | KR20220115611A (en) |
CN (1) | CN115151279A (en) |
AU (1) | AU2020403148A1 (en) |
CA (1) | CA3164353A1 (en) |
MX (1) | MX2022007202A (en) |
WO (1) | WO2021119516A1 (en) |
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EP4321530A3 (en) | 2018-09-27 | 2024-05-22 | Xilio Development, Inc. | Masked cytokine polypeptides |
CN111423510B (en) * | 2019-01-10 | 2024-02-06 | 迈威(上海)生物科技股份有限公司 | Recombinant anti-human PD-1 antibody and application thereof |
AU2021206449A1 (en) | 2020-01-10 | 2022-07-21 | Bright Peak Therapeutics Ag | Modified IL-2 polypeptides and uses thereof |
CN115667523A (en) | 2020-04-10 | 2023-01-31 | 西托姆克斯治疗公司 | Activatable cytokine constructs and related compositions and methods |
WO2022012428A1 (en) * | 2020-07-14 | 2022-01-20 | 迈威(上海)生物科技股份有限公司 | Anti-pd-1 antibody and stabilized preparation thereof |
WO2022165419A1 (en) | 2021-02-01 | 2022-08-04 | Kyverna Therapeutics, Inc. | Methods for increasing t-cell function |
KR20230157448A (en) | 2021-03-16 | 2023-11-16 | 싸이톰스 테라퓨틱스, 인크. | Masked activatable cytokine constructs and related compositions and methods |
US20230056336A1 (en) * | 2021-04-15 | 2023-02-23 | Kyverna Therapeutics, Inc. | Methods and compositions for treating disease using targeted foxp3+cd4+ t cells and cellular suicide agents |
EP4366780A1 (en) * | 2021-07-09 | 2024-05-15 | Bright Peak Therapeutics AG | Synthetic il-7 and il-7 immunocytokines |
EP4366778A1 (en) * | 2021-07-09 | 2024-05-15 | Bright Peak Therapeutics AG | Antibody conjugates and manufacture thereof |
US20230181754A1 (en) * | 2021-07-09 | 2023-06-15 | Bright Peak Therapeutics Ag | Modified checkpoint inhibitors and uses thereof |
WO2023281483A1 (en) * | 2021-07-09 | 2023-01-12 | Bright Peak Therapeutics Ag | Modified tnf-antibodies and uses thereof |
US20240116997A1 (en) | 2022-02-23 | 2024-04-11 | Bright Peak Therapeutics Ag | Activatable il-18 polypeptides |
WO2023222886A1 (en) | 2022-05-20 | 2023-11-23 | Depth Charge Ltd | Antibody-cytokine fusion proteins |
WO2023230594A1 (en) * | 2022-05-27 | 2023-11-30 | Regeneron Pharmaceuticals, Inc. | Interleukin-2 proproteins and uses thereof |
US20230391844A1 (en) * | 2022-06-04 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Interleukin-2 proproteins and uses thereof |
WO2024059899A1 (en) * | 2022-09-20 | 2024-03-28 | Currus Biologics Pty Ltd | Bispecific polypeptides and uses thereof |
CN116574192A (en) * | 2023-03-30 | 2023-08-11 | 上海妙聚生物科技有限公司 | Cytokine fusion protein capable of being conditionally released and activated, and preparation and application thereof |
Family Cites Families (14)
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EP1777294A1 (en) * | 2005-10-20 | 2007-04-25 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | IL-15Ralpha sushi domain as a selective and potent enhancer of IL-15 action through IL-15Rbeta/gamma, and hyperagonist (IL15Ralpha sushi -IL15) fusion proteins |
US20070160578A1 (en) * | 2005-12-14 | 2007-07-12 | The Gov. Of The Usa As Represented By The Secretary Of The Dep. Of Health And Human Services | Expansion of natural killer and CD8 T-cells with IL-15R/ligand activator complexes |
WO2011123683A2 (en) * | 2010-04-02 | 2011-10-06 | University Of Rochester | Protease activated cytokines |
CA2970385C (en) * | 2014-12-19 | 2023-04-04 | Jiangsu Hengrui Medicine Co., Ltd. | Interleukin 15 protein complex and use thereof |
PE20191494A1 (en) * | 2017-04-03 | 2019-10-21 | Hoffmann La Roche | IMMUNOCONJUGATES OF AN ANTI-PD-1 ANTIBODY WITH A MUTANT IL-2 OR IL-15 |
WO2019166946A1 (en) * | 2018-02-28 | 2019-09-06 | Pfizer Inc. | Il-15 variants and uses thereof |
WO2019173832A2 (en) * | 2018-03-09 | 2019-09-12 | AskGene Pharma, Inc. | Novel cytokine prodrugs |
US11524991B2 (en) * | 2018-04-18 | 2022-12-13 | Xencor, Inc. | PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof |
TW202011984A (en) * | 2018-04-18 | 2020-04-01 | 美商山可爾股份有限公司 | Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof |
CN110437339B (en) * | 2018-05-04 | 2021-08-13 | 免疫靶向有限公司 | Fusion protein type prodrug with interleukin 15 as active component |
WO2019246392A1 (en) * | 2018-06-22 | 2019-12-26 | Cugene Inc. | Cytokine-based bioactivatable drugs and methods of uses thereof |
EP3893917A4 (en) * | 2018-12-14 | 2023-01-11 | Proviva Therapeutics (Hong Kong) Limited | Il-15 compositions and methods of use thereof |
CN114341189A (en) * | 2019-06-12 | 2022-04-12 | 奥美药业有限公司 | Novel IL-15 prodrug and application thereof |
EP3997115A4 (en) * | 2019-07-12 | 2023-11-22 | Proviva Therapeutics (Hong Kong) Limited | Il-2 compositions and methods of use thereof |
-
2020
- 2020-12-11 US US17/784,305 patent/US20230093155A1/en active Pending
- 2020-12-11 WO PCT/US2020/064651 patent/WO2021119516A1/en active Application Filing
- 2020-12-11 CN CN202080097196.4A patent/CN115151279A/en active Pending
- 2020-12-11 EP EP20899199.2A patent/EP4072593A4/en active Pending
- 2020-12-11 MX MX2022007202A patent/MX2022007202A/en unknown
- 2020-12-11 JP JP2022535520A patent/JP2023506454A/en active Pending
- 2020-12-11 CA CA3164353A patent/CA3164353A1/en active Pending
- 2020-12-11 KR KR1020227024242A patent/KR20220115611A/en unknown
- 2020-12-11 AU AU2020403148A patent/AU2020403148A1/en active Pending
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