HRP20200093T1 - Humanizirane neljudske životinje s ograničenim lokusima imunoglobulinskog teškog lanca - Google Patents
Humanizirane neljudske životinje s ograničenim lokusima imunoglobulinskog teškog lanca Download PDFInfo
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- HRP20200093T1 HRP20200093T1 HRP20200093TT HRP20200093T HRP20200093T1 HR P20200093 T1 HRP20200093 T1 HR P20200093T1 HR P20200093T T HRP20200093T T HR P20200093TT HR P20200093 T HRP20200093 T HR P20200093T HR P20200093 T1 HRP20200093 T1 HR P20200093T1
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- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 title claims 18
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 title claims 18
- 108090000623 proteins and genes Proteins 0.000 claims 54
- 241000699666 Mus <mouse, genus> Species 0.000 claims 41
- 239000012634 fragment Substances 0.000 claims 11
- 102000004169 proteins and genes Human genes 0.000 claims 11
- 239000000427 antigen Substances 0.000 claims 9
- 102000036639 antigens Human genes 0.000 claims 9
- 108091007433 antigens Proteins 0.000 claims 9
- 238000000034 method Methods 0.000 claims 8
- 241001529936 Murinae Species 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 6
- 108700031127 mouse Adam6a Proteins 0.000 claims 6
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 3
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 3
- 230000003053 immunization Effects 0.000 claims 3
- 108020004414 DNA Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 230000004048 modification Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical group 0.000 claims 2
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims 1
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- 210000000628 antibody-producing cell Anatomy 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 210000004408 hybridoma Anatomy 0.000 claims 1
- 230000028993 immune response Effects 0.000 claims 1
- 238000002649 immunization Methods 0.000 claims 1
- 238000003780 insertion Methods 0.000 claims 1
- 230000037431 insertion Effects 0.000 claims 1
- 210000001165 lymph node Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000004044 response Effects 0.000 claims 1
- 210000000952 spleen Anatomy 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Humanized animals, e.g. knockin
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
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- A01K2207/00—Modified animals
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- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
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- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
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- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- C12N2800/00—Nucleic acids vectors
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- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
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Claims (14)
1. Miš koji u svom genomu sadrži:
(a) nepreuređenu humanu genomsku sekvencu koja obuhvaća jedan humani segment gena VH, jedan ili više humanih segmenata gena DH i jedan ili više humanih segmenata gena JH, naznačeno time, što su jedan humani segment gena VH, jedan ili više humanih segmenata gena DH i jedan ili više humanih segmenata gena JH operativno povezani s genom konstantne regije mišjeg imunoglobulinskog teškog lanca i naznačeno time, što jedan humani segment gena VH jest VH1-2, VH1-69, VH2-26, VH2-70 ili njegova polimorfna varijanta; i
(b) sekvencu koja šifrira mišji protein ADAM6a ili njegov funkcionalni fragment i sekvencu koja šifrira mišji protein ADAM6b ili njegov funkcionalni fragment, naznačeno time, što su mišji protein ADAM6a ili njegov funkcionalni fragment i mišji protein ADAM6b ili njegov funkcionalni protein funkcionalni u mužjaka miša, naznačeno time, što se predmetne šifrirajuće sekvence nalaze u položaju izvan lokusa ADAM6 miša divljeg tipa
tako da, kao odgovor na izlaganje antigenu, B stanice miša izražavaju varijabilne domene humanog teškog lanca izražene iz sekvence varijabilne regije humanog teškog lanca uključujući segment gena VH koji je identičan ili somatski hipermutirana verzija VH1-2, VH1-69, VH2-26, VH2-70 ili njegove polimorfne varijante; naznačeno time, što predmetni miš ne posjeduje funkcionalni endogeni gen ADAM6.
2. Miš prema patentnom zahtjevu 1, naznačen time, što:
(I) jedan humani segment gena VH je polimorfna varijanta VH1-2, VH1-69, VH2-26, VH2-70;
(II) šifrirajuće sekvence su prisutne na položaju u genomu miša izvan endogenog lokusa imunoglobulinskog teškog lanca;
(III) šifrirajuće sekvence su postavljene podređeno ili neposredno uz nepreuređenu humanu genomsku sekvencu;
(IV) nepreuređena humana genomska sekvenca nalazi se na endogenom lokusu imunoglobulinskog teškog lanca;
(V) nepreuređena humana genomska sekvenca nalazi se na endogenom lokusu imunoglobulinskog lakog lanca, a šifrirajuće sekvence nalaze se na položaju u genomu miša izvan endogenog lokusa imunoglobulinskog teškog lanca;
(VI) miš sadrži deleciju svih ili suštinski svih endogenih segmenata gena VH; ili
(VII) gen konstantne regije mišjeg imunoglobulinskog lakog lanca se nalazi na endogenom lokusu imunoglobulinskog teškog lanca.
3. Miš prema patentnom zahtjevu 1, naznačen time, što:
(I) jedan humani segment gena VH je VH1-69; ili
(II) jedan humani segment gena VH je VH1-2.
4. Miš prema patentnom zahtjevu 1, naznačen time, što:
(I) nepreuređena humana genomska sekvenca sadrži humani segment gena VH1-69, dvadeset sedam humanih segmenata gena DH i šest humanih segmenata gena JH; ili
(II) nepreuređena humana genomska sekvenca sadrži humani segment gena VH1-2, dvadeset sedam humanih segmenata gena DH i šest humanih segmenata gena JH.
5. Miš prema patentnom zahtjevu 1 ili 4, koji dodatno u svom genomu sadrži jedan ili više humanih segmenata gena Vκ i jedan ili više humanih segmenata Jκ, opcionalno naznačeno time, što se jedan ili više humanih segmenata gena Vκ i jedan ili više humanih segmenata gena Jκ nalaze na endogenom lokusu imunoglobulinskog lakog lanca.
6. Miš koji u svom genomu sadrži sekvencu nukleinske kiseline koja sadrži jedan humani segment gena VH, najmanje jedan humani segment gena DH i najmanje jedan humani segment gena JH, naznačeno time, što su jedan humani segment gena VH, jedan ili više humanih segmenata gena DH i jedan ili više humanih segmenata gena JH operativno povezani s genom konstantne regije mišjeg imunoglobulinskog teškog lanca i naznačeno time, što jedan humani segment gena VH jest VH1-2, VH1-69, VH2-26, VH2-70 ili njegova polimorfna varijanta, naznačeno time, što miš ne posjeduje funkcionalni endogeni gen ADAM6 i naznačeno time, što miš sadrži sekvence ektopijskog mišjeg ADAM6 koje šifriraju protein ADAM6a ili njegov funkcionalni fragment i protein ADAM6b ili njegov funkcionalni fragment.
7. Miš prema patentnom zahtjevu 6, naznačen time, što:
(I) sekvence ektopijskog mišjeg ADAM6 se nalaze na endogenom imunoglobulinskom lokusu; Ili
(II) sekvence ektopijskog mišjeg ADAM6 se nalaze u genomu miša na položaju izvan endogenog imunoglobulinskog lokusa.
8. Stanica ili tkivo dobiveno iz miša prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, što stanica ili miš sadrži
(a) nepreuređenu humanu genomsku sekvencu koja sadrži jedan humani segment gena VH, jedan ili više humanih segmenata gena DH i jedan ili više humanih segmenata gena JH, naznačeno time, što su jedan humani segment gena VH, jedan ili više humanih segmenata gena DH i jedan ili više humanih segmenata gena JH operativno povezani s genom konstantne regije mišjeg imunoglobulinskog teškog lanca i naznačeno time, što jedan humani segment gena VH jest VH1-2, VH1-69, VH2-26, VH2-70 ili njegova polimorfna varijanta; i
(b) sekvencu koja šifrira mišji protein ADAM6a ili njegov funkcionalni fragment i sekvencu koja šifrira mišji protein ADAM6b ili njegov funkcionalni fragment, naznačeno time, što su mišji protein ADAM6a ili njegov funkcionalni fragment i mišji protein ADAM6b ili njegov funkcionalni protein funkcionalni u mužjaka miša, naznačeno time, što se predmetne šifrirajuće sekvence nalaze u položaju izvan lokusa ADAM6 miša divljeg tipa
9. Metoda za proizvodnju humanog antitijela koje sadrži imunoglobulinski teški lanac dobiven iz jednog humanog segmenta gena VH, pri čemu se metoda sastoji od
(a) imunizacije miša prema bilo kojem patentnom zahtjevu od 1 do 7 pomoću interesnog antigena;
(b) omogućavanja predmetnom mišu da razvije imunološki odgovor na interesni antigen; i
(c) identifikacije ili izolacije sekvence varijabilne regije imunoglobulinskog teškog lanca koja šifrira varijabilnu domenu imunoglobulinskog teškog lanca antitijela koje stvara miš, naznačeno time, što se antitijelo vezuje za interesni antigen.
10. Metoda prema patentnom zahtjevu 9, naznačena time, što:
(I) varijabilna domena imunoglobulinskog teškog lanca je najmanje 75 %, najmanje 80 %, najmanje 85 %, najmanje 95 % ili najmanje 98 % identična SEQ ID NO: 5;
(II) varijabilna domena imunoglobulinskog teškog lanca sadrži SEQ ID NO: 5;
(III) varijabilna domena imunoglobulinskog teškog lanca je najmanje 75 %, najmanje 80 %, najmanje 85 %, najmanje 95 % ili najmanje 98 % identična SEQ ID NO: 64;
(IV) varijabilna domena imunoglobulinskog teškog lanca sadrži SEQ ID NO: 64.
11. Metoda za modifikaciju mišjeg lokusa imunoglobulinskog teškog lanca radi dobivanja miša čiji genom sadrži lokus imunoglobulinskog teškog lanca uključujući jedan humani segment VH, pri čemu se metoda sastoji od:
(a) postizanja prve modifikacije lokusa mišjeg imunoglobulinskog teškog lanca koja uključuje umetanje jednog humanog segmenta VH i dovodi do smanjenja ili eliminacije aktivnosti endogenog mišjeg ADAM6 kod mužjaka miša, naznačeno time, što jedan humani segment gena VH jest VH1-2, VH1-69, VH2-26, VH2-70 ili njegova polimorfna varijanta; i
(b) postizanja druge modifikacija miša radi vraćanja aktivnosti ADAM6 kod miša, koje se sastoji od izražavanja sekvence koja šifrira mišji protein ADAM6a ili njegov funkcionalni fragment naznačeno time, što su mišji protein ADAM6a ili njegov funkcionalni fragment i mišji protein ADAM6b ili njegov funkcionalni fragment funkcionalni kod mužjaka miša.
12. Metoda za dobivanje antitijela koje specifično djeluje protiv antigena, pri čemu se metoda sastoji od sljedećih koraka:
(a) imunizacije miša prema bilo kojem patentnom zahtjevu od 1 do 7 pomoću antigena;
(b) izolacije najmanje jedne stanice iz miša koja proizvodi antitijelo koje specifično djeluje protiv antigena; i
(c) uzgajanja najmanje jedne stanice koja proizvodi antitijelo iz koraka (b) i dobivanja predmetnog antitijela.
13. Metoda prema patentnom zahtjevu 12, naznačena time, što:
(I) uzgajanje iz koraka (c) se obavlja na najmanje jednoj hibridoma stanici proizvedenoj iz najmanje jedne stanice dobivene u koraku (b);
(II) najmanje jedna stanica dobivena u koraku (b) se dobiva iz slezene, limfnog čvora ili koštane srži miša iz koraka (a); Ili
(III) imunizacija pomoću antigena iz koraka (a) obavlja se pomoću proteina, DNK, kombinacije DNK i proteina ili stanica koje izražavaju antigen.
14. Upotreba miša prema bilo kojem patentnom zahtjevu od 1 do 7, radi dobivanja sekvence nukleinske kiseline koja šifrira varijabilnu domenu humanog imunoglobulinskog teškog lanca.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261658466P | 2012-06-12 | 2012-06-12 | |
| US201261663131P | 2012-06-22 | 2012-06-22 | |
| PCT/US2013/029624 WO2013187953A1 (en) | 2012-06-12 | 2013-03-07 | Humanized non-human animals with restricted immunoglobulin heavy chain loci |
| EP13710268.7A EP2858487B1 (en) | 2012-06-12 | 2013-03-07 | Humanized non-human animals with restricted immunoglobulin heavy chain loci |
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| HRP20200093T1 true HRP20200093T1 (hr) | 2020-04-03 |
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| HRP20200093TT HRP20200093T1 (hr) | 2012-06-12 | 2020-01-21 | Humanizirane neljudske životinje s ograničenim lokusima imunoglobulinskog teškog lanca |
| HRP20211126TT HRP20211126T1 (hr) | 2012-06-12 | 2021-07-14 | Humanizirane nehumane životinje s ograničenim lokusima imunoglobulinskog teškog lanca |
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| EP (3) | EP2858487B1 (hr) |
| JP (5) | JP2015519076A (hr) |
| KR (8) | KR102650439B1 (hr) |
| CN (1) | CN104540383B (hr) |
| AU (5) | AU2013204582B2 (hr) |
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| SG (3) | SG10201913429WA (hr) |
| SI (2) | SI3597037T1 (hr) |
| WO (1) | WO2013187953A1 (hr) |
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2016
- 2016-03-11 AU AU2016201612A patent/AU2016201612A1/en not_active Abandoned
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2017
- 2017-11-30 JP JP2017230304A patent/JP6697430B2/ja active Active
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2018
- 2018-03-01 AU AU2018201501A patent/AU2018201501B2/en active Active
- 2018-12-17 US US16/222,951 patent/US10542735B2/en active Active
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2019
- 2019-12-04 US US16/703,116 patent/US11559050B2/en active Active
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2020
- 2020-01-10 CY CY20201100023T patent/CY1122482T1/el unknown
- 2020-01-21 HR HRP20200093TT patent/HRP20200093T1/hr unknown
- 2020-03-27 AU AU2020202185A patent/AU2020202185B2/en active Active
- 2020-04-15 US US16/849,782 patent/US11666040B2/en active Active
- 2020-04-24 JP JP2020077376A patent/JP7106596B2/ja active Active
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2021
- 2021-07-14 HR HRP20211126TT patent/HRP20211126T1/hr unknown
- 2021-07-20 CY CY20211100661T patent/CY1124320T1/el unknown
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2022
- 2022-04-25 JP JP2022071670A patent/JP2022090103A/ja active Pending
- 2022-12-22 AU AU2022291579A patent/AU2022291579A1/en active Pending
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2023
- 2023-04-20 US US18/137,110 patent/US20240065238A1/en active Pending
- 2023-09-11 JP JP2023147111A patent/JP2023165683A/ja active Pending
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