HRP20171193T1 - Proizvodnja vezivnih molekula - Google Patents
Proizvodnja vezivnih molekula Download PDFInfo
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- HRP20171193T1 HRP20171193T1 HRP20171193TT HRP20171193T HRP20171193T1 HR P20171193 T1 HRP20171193 T1 HR P20171193T1 HR P20171193T T HRP20171193T T HR P20171193TT HR P20171193 T HRP20171193 T HR P20171193T HR P20171193 T1 HRP20171193 T1 HR P20171193T1
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- Croatia
- Prior art keywords
- cells
- sequences
- repertoire
- population
- antibodies
- Prior art date
Links
- 238000000034 method Methods 0.000 claims 14
- 210000003719 b-lymphocyte Anatomy 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 7
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 239000000427 antigen Substances 0.000 claims 5
- 102000036639 antigens Human genes 0.000 claims 5
- 108091007433 antigens Proteins 0.000 claims 5
- 230000003321 amplification Effects 0.000 claims 4
- 238000003199 nucleic acid amplification method Methods 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 2
- 238000004458 analytical method Methods 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 210000001165 lymph node Anatomy 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 238000012163 sequencing technique Methods 0.000 claims 2
- 210000000952 spleen Anatomy 0.000 claims 2
- 230000009261 transgenic effect Effects 0.000 claims 2
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 claims 1
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 230000022534 cell killing Effects 0.000 claims 1
- 210000004748 cultured cell Anatomy 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 238000011990 functional testing Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 238000011830 transgenic mouse model Methods 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/06—Biochemical methods, e.g. using enzymes or whole viable microorganisms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1018—Orthomyxoviridae, e.g. influenza virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B30/00—Methods of screening libraries
- C40B30/04—Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (12)
1. Postupak za proizvodnju najmanje dva antitijela koja se vezuju za odabrani antigen ili epitop od interesa, pri čemu navedeni postupak sadrži najmanje slijedeće korake:
a) osiguravanje populacije B stanica koje eksprimiraju ograničeni VL repertoar koji ne sadrži više od 10 različitih VL regija, pri čemu uglavnom sve od navedenih B stanica nose najmanje jedan VL, pri čemu je navedena populacija B stanica dobivena od transgenične ne-humane životinje koja nosi ograničeni VL repertoar, pri čemu se navedeni ograničeni VL repertoar sastoji od manje od 10 VL, pri čemu je navedena ne-humana životinja imunizirana s navedenim antigenom, i pri čemu navedena populacija B stanica sadrži B satanice dobivene iz slezine i/ili najmanje jednog limfnog čvora,
b) dobivanje nukleinskih kiselina iz navedenih B stanica,
c) po izboru, amplifikacija sekvenci nukleinske kiseline koje kodiraju varijabilne regije teškog lanca imunoglobulina u navedenom uzorku,
d) najmanje djelomično sekvenciranje uglavnom svih dobivenih nukleinskih kiselina iz koraka b) ili proizvoda amplifikacije iz koraka c),
e) provođenje analize učestalosti VH sekvenci iz koraka d), koje sadrže CDR3 sekvence teškog lanca,
f) odabir 20 najčešćih VH sekvenci,
g) osiguravanje stanice domaćina s najmanje jednim vektorom koji sadrži najmanje jednu od navedenih VH sekvenci i najmanje jednu VL sekvencu navedenog ograničenog VL repertoara,
h) kultiviranje navedenih stanica domaćina i omogućavanje ekspresije VH i VL polipeptida,
i) dobivanje navedenih antitijela.
2. Postupak za proizvodnju najmanje dva antitijela koja se vezuju za odabrani antigen ili epitop od interesa, pri čemu navedeni postupak sadrži najmanje slijedeće korake:
a) osiguravanje populacije B stanica koje eksprimiraju ograničeni VL repertoar koji ne sadrži više od 10 različitih VL regija, pri čemu u osnovi sve od navedenih B stanica nose najmanje jedan VL, pri čemu je navedena populacija B stanica dobivena iz transgenične ne-humane životinje koja nosi ograničeni VL repertoar, pri čemu se navedeni ograničeni VL repertoar sastoji od manje od 10 VL, pri čemu je navedena ne-humana životinja imunizirana s navedenim antigenom, i pri čemu navedena populacija B stanica sadrži B stanica dobivene iz slezine i/ili najmanje jednog limfnog čvora,
b) dobivanje nukleinskih kiselina iz navedenih B stanica,
c) izborno, amplifikaciju sekvenci nukleinske kiseline koje kodiraju varijabilne regije teškog lanca imunoglobulina u navedenom uzorku,
d) najmanje djelomično sekvenciranje uglavnom svih dobivenih nukleinskih kiselina iz koraka b) ili proizvoda amplifikacije iz koraka c),
e) izvođenje analize učestalosti VH sekvenci iz koraka d), koje sadrže CDR3 sekvence teškog lanca,
f) selekciju 20 najčešćih VH sekvenci,
g) osiguravanje stanica domaćina s najmanje jednim vektorom koji sadrži najmanje jednu od navedenih VH sekvenci, pri čemu navedene stanice domaćini sadrže sekvencu nukleinske kiseline koja kodira zajednički laki lanac koji je sposoban da se uparuje s navedenim VH,
h) kultiviranje navedenih stanica domaćina i omogućavanje ekspresije VH i VL polipeptida,
i) dobivanje navedenih antitijela.
3. Postupak sukladno patentnom zahtjevu 1 ili 2, koji dalje sadrži uzimanje uzorka od navedenih kultiviranih stanica, pri čemu uzorak sadrži najmanje jedno od navedenih antitijela, i podvrgavanje uzorka barem jednom funkcionalnom testu, i odabir najmanje jedne stanice koja eksprimira protitijelo s željenom specifičnosti vezivanja, afinitetom, neutralizujućim djelovanjem, aktivnošću ubijanja tumorskih stanica i/ili inhibicijskom aktivnošću proliferacije.
4. Postupak sukladno patentnom zahtjevu 1 ili 2 ili 3, da nadalje sadrži navedene stanice domaćina za ekspresiju spomenutog najmanje jednog VH i VL u obliku imunoglobulina.
5. Postupak sukladno patentnom zahtjevu 4, naznačen time što navedeni u obliku imunoglobulina sadrži najmanje jedno monospecifično antitijelo, i/ili najmanje jedno bispecifično antitijelo.
6. Postupak sukladan bilo kojem od patentnih zahtjeva 1-5, naznačen time što se navedeni ograničeni VL repertoar sastoji od jednog VL.
7. Postupak sukladan bilo kojem od patentnih zahtjeva 1-6, naznačen time što se navedeni ograničeni VL repertoar sastoji od jednog redizajniranog humanog VL, poželjno humanog lakog lanca IGKV1-39.
8. Postupak sukladan bilo kojem od patentnih zahtjeva 1-7, naznačen time što je navedena populacija B stanica dobivena iz transgeničnog miša koji je imuniziran antigenom.
9. Postupak sukladno patentnom zahtjevu 1, naznačen time što je odabrano 50 najčešćih VH sekvenci.
10. Postupak sukladno patentnom zahtjevu 1, naznačen time što je odabrano 100 najčešćih VH sekvenci.
11. Postupak sukladno patentnom zahtjevu 1, naznačen time što je odabrano 200 najčešćih VH sekvenci.
12. Postupak sukladno bilo kojem od patentnih zahtjeva 1-11, koji dodatno sadrži pripremu smjese antitijela, poželjno sadrži bispecifična antitijela.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161539116P | 2011-09-26 | 2011-09-26 | |
| EP12186010.0A EP2604625B1 (en) | 2011-09-26 | 2012-09-26 | Generation of binding molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20171193T1 true HRP20171193T1 (hr) | 2017-12-01 |
Family
ID=47010271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20171193TT HRP20171193T1 (hr) | 2011-09-26 | 2017-08-02 | Proizvodnja vezivnih molekula |
Country Status (16)
| Country | Link |
|---|---|
| US (5) | US9145588B2 (hr) |
| EP (3) | EP3263597A1 (hr) |
| AU (4) | AU2012233037B2 (hr) |
| CA (1) | CA2791109C (hr) |
| CY (1) | CY1119717T1 (hr) |
| DK (1) | DK2604625T3 (hr) |
| ES (1) | ES2636239T3 (hr) |
| HK (1) | HK1247938A1 (hr) |
| HR (1) | HRP20171193T1 (hr) |
| HU (1) | HUE034386T2 (hr) |
| LT (1) | LT2604625T (hr) |
| ME (1) | ME02817B (hr) |
| PL (1) | PL2604625T3 (hr) |
| PT (1) | PT2604625T (hr) |
| RS (1) | RS56302B1 (hr) |
| SI (1) | SI2604625T1 (hr) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| EP2450377A1 (en) | 2006-09-07 | 2012-05-09 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza virus H5N1 and uses thereof |
| EP3916011A1 (en) | 2009-06-26 | 2021-12-01 | Regeneron Pharmaceuticals, Inc. | Readily isolated bispecific antibodies with native immunoglobulin format |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| RU2724663C2 (ru) | 2010-02-08 | 2020-06-25 | Ридженерон Фармасьютикалз, Инк. | Мышь с общей легкой цепью |
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| CA2791109C (en) | 2011-09-26 | 2021-02-16 | Merus B.V. | Generation of binding molecules |
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| AU2013249985B2 (en) | 2012-04-20 | 2017-11-23 | Merus N.V. | Methods and means for the production of Ig-like molecules |
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| JP6771385B2 (ja) | 2014-02-28 | 2020-10-21 | メルス ナムローゼ フェンノートシャップ | 二重特異性抗体および医薬組成物 |
| KR102601491B1 (ko) | 2014-03-21 | 2023-11-13 | 리제너론 파마슈티칼스 인코포레이티드 | 단일 도메인 결합 단백질을 생산하는 비-인간 동물 |
| GB201500464D0 (en) | 2015-01-12 | 2015-02-25 | Crescendo Biolog Ltd | Method of producing optimised therapeutic molecules |
| CN107438622A (zh) | 2015-03-19 | 2017-12-05 | 瑞泽恩制药公司 | 选择结合抗原的轻链可变区的非人动物 |
| CA2991880A1 (en) | 2015-07-10 | 2017-01-19 | Merus N.V. | Human cd3 binding antibody |
| SI3365373T1 (sl) | 2015-10-23 | 2021-08-31 | Merus N.V. | Vezne molekule, ki zaviranjo rast raka |
| WO2017165464A1 (en) | 2016-03-21 | 2017-09-28 | Elstar Therapeutics, Inc. | Multispecific and multifunctional molecules and uses thereof |
| CA3026088A1 (en) | 2016-06-03 | 2017-12-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing exogenous terminal deoxynucleotidyltransferase |
| WO2018151820A1 (en) | 2017-02-16 | 2018-08-23 | Elstar Therapeutics, Inc. | Multifunctional molecules comprising a trimeric ligand and uses thereof |
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- 2012-09-26 SI SI201231020T patent/SI2604625T1/sl unknown
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| US20130096020A1 (en) | 2013-04-18 |
| EP2604625B1 (en) | 2017-06-28 |
| ME02817B (me) | 2018-01-20 |
| CA2791109A1 (en) | 2013-03-26 |
| HUE034386T2 (en) | 2018-02-28 |
| US20200247908A1 (en) | 2020-08-06 |
| ES2636239T3 (es) | 2017-10-05 |
| AU2012233037B2 (en) | 2015-10-29 |
| US9908946B2 (en) | 2018-03-06 |
| US20230160105A1 (en) | 2023-05-25 |
| US10647781B2 (en) | 2020-05-12 |
| EP2604625A1 (en) | 2013-06-19 |
| CA2791109C (en) | 2021-02-16 |
| RS56302B1 (sr) | 2017-12-29 |
| US20160130367A1 (en) | 2016-05-12 |
| CY1119717T1 (el) | 2018-09-05 |
| LT2604625T (lt) | 2017-09-25 |
| AU2020244368A1 (en) | 2020-10-29 |
| AU2016200316A1 (en) | 2016-02-11 |
| AU2018201328A1 (en) | 2018-03-15 |
| AU2012233037A1 (en) | 2013-04-11 |
| SI2604625T1 (sl) | 2017-11-30 |
| US9145588B2 (en) | 2015-09-29 |
| HK1247938A1 (zh) | 2018-10-05 |
| PT2604625T (pt) | 2017-08-11 |
| EP4086282A1 (en) | 2022-11-09 |
| AU2018201328B2 (en) | 2020-07-02 |
| AU2016200316B2 (en) | 2017-11-23 |
| EP3263597A1 (en) | 2018-01-03 |
| PL2604625T3 (pl) | 2017-12-29 |
| DK2604625T3 (en) | 2017-08-21 |
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