HRP20210759T1 - Poboljšana molekula polipeptida dvostruke specifičnosti - Google Patents
Poboljšana molekula polipeptida dvostruke specifičnosti Download PDFInfo
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- HRP20210759T1 HRP20210759T1 HRP20210759TT HRP20210759T HRP20210759T1 HR P20210759 T1 HRP20210759 T1 HR P20210759T1 HR P20210759T T HRP20210759T T HR P20210759TT HR P20210759 T HRP20210759 T HR P20210759T HR P20210759 T1 HRP20210759 T1 HR P20210759T1
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims 34
- 229920001184 polypeptide Polymers 0.000 title claims 31
- 102000004196 processed proteins & peptides Human genes 0.000 title claims 31
- 230000009977 dual effect Effects 0.000 title claims 11
- 108091008874 T cell receptors Proteins 0.000 claims 7
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 7
- 210000004027 cell Anatomy 0.000 claims 6
- 230000035772 mutation Effects 0.000 claims 6
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- -1 CD11c Proteins 0.000 claims 3
- 239000013604 expression vector Substances 0.000 claims 3
- 101710160107 Outer membrane protein A Proteins 0.000 claims 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 2
- 239000012636 effector Substances 0.000 claims 2
- 230000030279 gene silencing Effects 0.000 claims 2
- 210000002865 immune cell Anatomy 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 claims 1
- 108010009992 CD163 antigen Proteins 0.000 claims 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims 1
- 102100032912 CD44 antigen Human genes 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 claims 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 1
- 102100035716 Glycophorin-A Human genes 0.000 claims 1
- 102000006354 HLA-DR Antigens Human genes 0.000 claims 1
- 108010058597 HLA-DR Antigens Proteins 0.000 claims 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims 1
- 101000980744 Homo sapiens C-C chemokine receptor type 3 Proteins 0.000 claims 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 claims 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims 1
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 claims 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims 1
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 claims 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 claims 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 claims 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 claims 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 claims 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims 1
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims 1
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 claims 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims 1
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 claims 1
- 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 claims 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims 1
- 101000971513 Homo sapiens Natural killer cells antigen CD94 Proteins 0.000 claims 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims 1
- 101000897042 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 claims 1
- 101001071312 Homo sapiens Platelet glycoprotein IX Proteins 0.000 claims 1
- 101001070790 Homo sapiens Platelet glycoprotein Ib alpha chain Proteins 0.000 claims 1
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims 1
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 claims 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims 1
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims 1
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims 1
- 102000009438 IgE Receptors Human genes 0.000 claims 1
- 108010073816 IgE Receptors Proteins 0.000 claims 1
- 102100021317 Inducible T-cell costimulator Human genes 0.000 claims 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 claims 1
- 102100022338 Integrin alpha-M Human genes 0.000 claims 1
- 102100022297 Integrin alpha-X Human genes 0.000 claims 1
- 102100025390 Integrin beta-2 Human genes 0.000 claims 1
- 102100032999 Integrin beta-3 Human genes 0.000 claims 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 claims 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims 1
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 claims 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims 1
- 102100025136 Macrosialin Human genes 0.000 claims 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 claims 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims 1
- 102100021462 Natural killer cells antigen CD94 Human genes 0.000 claims 1
- 102000003729 Neprilysin Human genes 0.000 claims 1
- 108090000028 Neprilysin Proteins 0.000 claims 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims 1
- 102100021969 Nucleotide pyrophosphatase Human genes 0.000 claims 1
- 102100036851 Platelet glycoprotein IX Human genes 0.000 claims 1
- 102100034173 Platelet glycoprotein Ib alpha chain Human genes 0.000 claims 1
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims 1
- 102100025831 Scavenger receptor cysteine-rich type 1 protein M130 Human genes 0.000 claims 1
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 claims 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims 1
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 230000000447 dimerizing effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000833 heterodimer Substances 0.000 claims 1
- 239000012642 immune effector Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
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- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (15)
1. Molekula polipeptida dvostruke specifičnosti koja obuhvaća prvi polipeptidni lanac i drugi polipeptidni lanac, pri čemu:
a) prvi polipeptidni lanac sadrži
ai) prvu varijabilnu domenu (VD1) antitijela,
aii) prvu varijabilnu domenu (VR1) T-staničnog receptora (TCR) i
aiii) prvi povezivač (LINK1) koji povezuje spomenute domene;
b) drugi polipeptidni lanac sadrži
bi) drugu varijabilnu domenu (VR2) TCR-a,
bi) drugu varijabilnu domenu (VD2) antitijela, i
biii) drugi povezivač (LINK2) koji povezuje spomenute domene;
pri čemu se spomenuta prva varijabilna domena (VD1) i spomenuta druga varijabilna domena (VD2) povezuju kako bi se stvorilo prvo vezno mjesto (VD1)(VD2) koje specifično veže površinski antigen ljudske imunološke efektorske stanice;
pri čemu je prva varijabilna domena (VR1) jedna od TCR Vα domene i TCR Vβ domene, a druga varijabilna domena (VR2) je druga od TCR Vα domene i TCR Vβ domene, spomenuta prva varijabilna domena (VR1 ) i spomenuta druga varijabilna domena (VR2) povezuju se da bi stvorile drugo vezno mjesto (VR1) (VR2) koje se specifično veže za MHC-povezani peptidni epitop;
pri čemu su spomenuta dva polipeptidna lanca spojena s humanim IgG zglobnim domenama i/ili humanim IgG Fc domenama ili njihovim dimerizirajućim dijelovima;
pri čemu su navedena dva polipeptidna lanca povezana kovalentnim i/ili nekovalentnim vezama između spomenutih zglobnih domena i/ili Fc-domena;
pri čemu je spomenuta polipeptidna molekula dvostruke specifičnosti sposobna istodobno vezati molekulu stanične površine i MHC-povezani peptidni epitop; i
pri čemu je redoslijed varijabilnih domena u dva polipeptidna lanca odabran između VD1-VR1 i VR2-VD2 ili VD2-VR2 i VR1-VD1.
2. Molekula polipeptida dvostruke specifičnosti u skladu s patentnim zahtjevom 1, pri čemu sekvence linkera LINK1 i/ili LINK2 sadrže najmanje jedan motiv sekvence odabran između GGGS, GGGGS, TVLRT, TVSSAS i TVLSSAS.
3. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 1 ili 2, pri čemu spomenuti prvi i drugi polipeptidni lanac nadalje sadrže najmanje zglobnu domenu i Fc domenu ili njihove dijelove izvedene iz humanog IgG1, IgG2 ili IgG4, pri čemu navedena Fc domena poželjno sadrži barem jednu mutaciju efektorske funkcije prigušivanja u slijedu SEQ ID br. 50 (ELLGGP) humanog IgG1, po mogućnosti gdje je navedena mutacija utišavanja efektorske funkcije generirana jednom ili više mutacija E1P, L2V, L3A i bez ostatka na položaju 4 SEQ ID br. 50.
4. Molekula polipeptida dvostruke specifičnosti u skladu s patentnim zahtjevom 3, pri čemu navedena Fc domena sadrži CH3 domenu koja sadrži barem jednu mutaciju koja olakšava stvaranje heterodimera, po mogućnosti, gdje spomenute mutacije sadrže odgovarajuće mutacije.
5. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 3 ili 4, pri čemu navedena Fc domena sadrži CH2 i CH3 domenu(e) koje sadrže najmanje dva dodatna ostatka cisteina.
6. Molekula polipeptida dvostruke specifičnosti u skladu s bilo kojim od patentnih zahtjeva 1 do 5, pri čemu spomenute domene izvedene od antitijela VD1 i VD2 prikazuju konstruirani disulfidni most koji uvodi kovalentnu vezu između VD1 i VD2 i gdje se navedeni cisteini uvode u okvirno područje (FR) 4 u slučaj VL i okvirno područje 2 u slučaju VH.
7. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 1 do 6, pri čemu je poznato da spomenuta molekula površinske stanice inducira aktivaciju imunoloških stanica ili je barem jedna odabrana iz skupine koju čine CD3, CD4, CD7, CD8, CD10 , CD11b, CD11c, CD14, CD16, CD18, CD22, CD25, CD28, CD32a, CD32b, CD33, CD41, CD41b, CD42a, CD42b, CD44, CD45RA, CD49, CD55, CD56, CD61, CD64, CD68, CD94, CD90 , CD117, CD123, CD125, CD134, CD137, CD152, CD163, CD193, CD203c, CD235a, CD278, CD279, CD287, Nkp46, NKG2D, GITR, FcεRI, TCRα/β i TCRγ/δ, HLA-DR, po mogućnosti molekula stanične površine je CD3γ, CD3δ ili CD3ε.
8. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 1 do 7, pri čemu prvi polipeptidni lanac sadrži SEQ ID br. 28, SEQ ID br. 29 i SEQ ID br. 30; a drugi polipeptidni lanac sadrži SEQ ID br. 31, SEQ ID br. 32 i SEQ ID br. 30.
9. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem zahtjevu od 3 do 8, pri čemu Fc regija u prvom polipeptidnom lancu sadrži SEQ ID br. 26 ili SEQ ID br. 47 (Fc1), a Fc regija u drugom polipeptidnom lancu SEQ ID br. 27 ili SEQ ID br. 48 (Fc2).
10. Molekula polipeptida dvostruke specifičnosti prema zahtjevu 1, pri čemu prvi lanac polipeptida sadrži SEQ ID br. 16, SEQ ID br. 43, SEQ ID br. 45, SEQ ID br. 51, SEQ ID br. 53, SEQ ID br. 55, ili SEQ ID br. 57, a pri čemu drugi polipeptidni lanac sadrži SEQ ID br. 17, SEQ ID 44, SEQ ID br. 46, SEQ ID br. 52, SEQ ID br. 54, SEQ ID br. 56, ili SEQ ID br. 58.
11. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 1 do 10, pri čemu je spomenuto prvo mjesto vezanja (VD1)(VD2) koje veže stanični površinski antigen spomenutih imunih stanica humanizirano; i/ili navedeno drugo vezno mjesto (VR1)(VR2) koje veže spomenuti MHC-povezani peptidni epitop je zrelo u afinitetu i/ili sazrelo za stabilnost.
12. Nukleinska kiselina koja kodira prvi polipeptidni lanac i/ili drugi polipeptidni lanac prema bilo kojem od zahtjeva 1 do 11, ili ekspresijski vektor koji sadrži najmanje jednu od spomenutih nukleinskih kiselina.
13. Stanica domaćin koja sadrži i po potrebi eksprimira vektor kako je definirano u zahtjevu 12.
14. Farmaceutski pripravak, koji sadrži molekulu polipeptida dvostruke specifičnosti prema bilo kojem zahtjevu od 1 do 11, nukleinsku kiselinu ili ekspresijski vektor prema zahtjevu 12 ili stanicu prema zahtjevu 13, zajedno s jednim ili više farmaceutski prihvatljivih nosača ili pomoćnih tvari.
15. Polipeptidna molekula dvostruke specifičnosti prema bilo kojem od zahtjeva 1 do 11, nukleinska kiselina ili ekspresijski vektor prema zahtjevu 12, stanica prema zahtjevu 13 ili farmaceutski pripravak prema zahtjevu 14, za uporabu u medicini, poželjno za upotrebu u prevenciji ili liječenju zaraznih bolesti.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762532713P | 2017-07-14 | 2017-07-14 | |
| DE102017115966.5A DE102017115966A1 (de) | 2017-07-14 | 2017-07-14 | Polypeptidmolekül mit verbesserter zweifacher Spezifität |
| DE102017119866 | 2017-08-30 | ||
| US201862658318P | 2018-04-16 | 2018-04-16 | |
| DE102018108995 | 2018-04-16 | ||
| EP18740829.9A EP3652215B1 (en) | 2017-07-14 | 2018-07-13 | Improved dual specificity polypeptide molecule |
| PCT/EP2018/069157 WO2019012141A1 (en) | 2017-07-14 | 2018-07-13 | IMPROVED POLYPEPTIDE MOLECULE WITH DOUBLE SPECIFICITY |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20210759T1 true HRP20210759T1 (hr) | 2021-06-11 |
Family
ID=70848164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20210759TT HRP20210759T1 (hr) | 2017-07-14 | 2021-05-12 | Poboljšana molekula polipeptida dvostruke specifičnosti |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JP2021019626A (hr) |
| CL (2) | CL2020000098A1 (hr) |
| HR (1) | HRP20210759T1 (hr) |
| IL (2) | IL272046A (hr) |
| PH (2) | PH12020500095A1 (hr) |
| ZA (1) | ZA202000636B (hr) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2968520T1 (sl) * | 2013-03-14 | 2022-01-31 | Macrogenics, Inc. | Bispecifične molekule, ki so imunoreaktivne z imunskimi efektorskimi celicami, ki izražajo aktivacijski receptor |
-
2020
- 2020-01-13 CL CL2020000098A patent/CL2020000098A1/es unknown
- 2020-01-13 CL CL2020000097A patent/CL2020000097A1/es unknown
- 2020-01-14 IL IL272046A patent/IL272046A/en unknown
- 2020-01-14 IL IL272045A patent/IL272045A/en unknown
- 2020-01-14 PH PH12020500095A patent/PH12020500095A1/en unknown
- 2020-01-14 PH PH12020500098A patent/PH12020500098A1/en unknown
- 2020-01-30 ZA ZA2020/00636A patent/ZA202000636B/en unknown
- 2020-10-23 JP JP2020177784A patent/JP2021019626A/ja active Pending
-
2021
- 2021-05-12 HR HRP20210759TT patent/HRP20210759T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2021019626A (ja) | 2021-02-18 |
| IL272045A (en) | 2020-03-31 |
| ZA202000636B (en) | 2021-07-28 |
| IL272046A (en) | 2020-03-31 |
| CL2020000098A1 (es) | 2020-05-29 |
| CL2020000097A1 (es) | 2020-05-29 |
| PH12020500098A1 (en) | 2020-12-07 |
| PH12020500095A1 (en) | 2020-12-07 |
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