HRP20191333T1 - Glodavci koji izražavaju sekvence imunoglobulina osjetljive na ph vrijednost - Google Patents
Glodavci koji izražavaju sekvence imunoglobulina osjetljive na ph vrijednost Download PDFInfo
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- HRP20191333T1 HRP20191333T1 HRP20191333TT HRP20191333T HRP20191333T1 HR P20191333 T1 HRP20191333 T1 HR P20191333T1 HR P20191333T T HRP20191333T T HR P20191333TT HR P20191333 T HRP20191333 T HR P20191333T HR P20191333 T1 HRP20191333 T1 HR P20191333T1
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- 241000283984 Rodentia Species 0.000 title claims 43
- 108060003951 Immunoglobulin Proteins 0.000 title claims 18
- 102000018358 immunoglobulin Human genes 0.000 title claims 18
- 235000014304 histidine Nutrition 0.000 claims 61
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 59
- 108020004705 Codon Proteins 0.000 claims 57
- 150000007523 nucleic acids Chemical group 0.000 claims 34
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 33
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 23
- 108090000623 proteins and genes Proteins 0.000 claims 22
- 210000004602 germ cell Anatomy 0.000 claims 21
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 17
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 17
- 238000003780 insertion Methods 0.000 claims 17
- 230000037431 insertion Effects 0.000 claims 17
- 238000006467 substitution reaction Methods 0.000 claims 17
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 11
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims 10
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 claims 10
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 claims 10
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 claims 10
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims 10
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 claims 10
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 10
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 claims 8
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims 7
- 238000000034 method Methods 0.000 claims 6
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 5
- 239000000427 antigen Substances 0.000 claims 4
- 108091007433 antigens Proteins 0.000 claims 4
- 102000036639 antigens Human genes 0.000 claims 4
- 150000002411 histidines Chemical class 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 3
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 claims 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 2
- 241000699800 Cricetinae Species 0.000 claims 1
- 101150097493 D gene Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
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Claims (18)
1. Genetski modificirani glodavac koji u svojoj zametnoj liniji sadrži lokus imunoglobulina koji sadrži nepreuređenu humanu sekvencu varijabilne regije imunoglobulina operativno povezanu sa sekvencom konstantne regije imunoglobulina, naznačen time, što nepreuređena humana sekvenca varijabilne regije imunoglobulina sadrži supstituciju najmanje jednog nehistidinskog kodona histidinskim kodonom ili umetanje najmanje jednog histidinskog kodona, u sekvenci nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR), naznačeno time, što histidinski kodon nije šifriran odgovarajućim humanim segmentom gena zametne linije divljeg tipa.
2. Glodavac prema patentnom zahtjevu 1, naznačen time, što:
(I) glodavac sadrži prvi i drugi varijabilni lokus imunoglobulina, naznačen time, što najmanje prvi ili najmanje drugi varijabilni lokus imunoglobulina sadrži nepreuređenu humanu sekvencu gena varijabilne regije imunoglobulina koja sadrži umetanje najmanje jednog histidinskog kodona ili supstituciju najmanje jednog nehistidinskog kodona najmanje jednim histidinskim kodonom; ili
(II) umetanje histidinskog kodona je u CDR-u odabranom iz CDR1 teškog lanca, CDR2 teškog lanca, CDR3 teškog lanca, CDR1 lakog lanca, CDR2 lakog lanca, CDR3 lakog lanca i njihove kombinacije; ili
(III) nepreuređena humana sekvenca gena varijabilne regije imunoglobulina u varijabilnom lokusu imunoglobulina sadrži klaster od 2, 3, 4 ili 5 histidina koji su supstitucije histidinskog kodona nehistidinskim kodonom i/ili umetanja histidinskih kodona.
3. Glodavac prema patentnom zahtjevu 2(I), naznačen time, što prvi i drugi varijabilni lokus imunoglobulina svaki sadrži nepreuređenu humanu sekvencu gena varijabilne regije imunoglobulina koja sadrži supstituciju najmanje jednog nehistidinskog kodona najmanje jednim histidinskim kodonom ili umetanje najmanje jednog histidinskog kodona.
4. Glodavac prema patentnom zahtjevu 3, naznačen time, što:
(I) prvi varijabilni lokus imunoglobulina je nepreuređeni humani varijabilni lokus imunoglobulinskog teškog lanca (nepreuređeni segmenti V, D, J); ili
(II) drugi varijabilni lokus imunoglobulina je nepreuređeni humani lokus imunoglobulinskog lakog lanca (nepreuređeni segmenti V, J).
5. Glodavac prema patentnom zahtjevu 4 (I), naznačen time, što:
(a) nepreuređeni humani varijabilni lokus imunoglobulinskog teškog lanca sadrži nepreuređene humane segmente V, D i J;
(b) nepreuređeni humani lokus imunoglobulinskog teškog lanca sadrži nepreuređene humane segmente V, sintetički segment D koji sadrži sponu i humani segment J, opcionalno naznačen time, što sintetički segment D sadrži najmanje jedan histidinski kodon;
(c) drugi varijabilni lokus imunoglobulina sadrži preuređenu varijabilnu sekvencu gena imunoglobulinskog lakog lanca (preuređena sekvenca VJ); ili
(d) nepreuređeni humani lokus imunoglobulinskog teškog lanca sadrži humane segmente gena D koji su invertirani u pogledu smjera lokusa imunoglobulinskog teškog lanca.
6. Glodavac prema patentnom zahtjevu 2(I), naznačen time, što je najmanje jedan prvi varijabilni lokus imunoglobulina ili drugi varijabilni lokus imunoglobulina operativno povezan s endogenom glodarskom sekvencom nukleinske kiseline konstantne regije na endogenom glodarskom lokusu imunoglobulina.
7. Glodavac prema patentnom zahtjevu 5(a), naznačen time, što su nepreuređeni humani segmenti V, D, J operativno povezani s endogenom nehumanom sekvencom nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca, opcionalno operativno povezani s endogenom glodarskom sekvencom nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca na endogenom glodarskom lokusu imunoglobulina.
8. Genetski modificirani glodavac, koji sadrži
humanu nepreuređenu sekvencu varijabilne regije imunoglobulinskog teškog lanca koja sadrži humane segmente VH, D i JH, naznačeno time, što je humana nepreuređena sekvenca varijabilne regije imunoglobulinskog teškog lanca operativno povezana sa sekvencom gena konstantne regije imunoglobulinskog teškog lanca, naznačeno time, što jedan ili više humanih segmenata gena VH, D i JH sadrže najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom i/ili najmanje jedno umetanje histidinskog kodona, u sekvenci nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR), naznačeno time, što supstituirani ili umetnuti histidinski kodon nije šifriran odgovarajućim humanim segmentom gena zametne linije divljeg tipa; i
humanu nepreuređenu sekvencu nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca koja sadrži humane segmente VL i J, naznačeno time, što je humana nepreuređena sekvenca nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca operativno povezana sa sekvencom gena konstantne regije imunoglobulinskog lakog lanca, naznačeno time, što jedan ili više segmenata gena VL i JL sadrže najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom i/ili najmanje jedno umetanje histidinskog kodona, u sekvenci nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR), naznačeno time, što supstituirani ili umetnuti histidinski kodon humane nepreuređene sekvence nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca nije šifriran odgovarajućim humanim segmentom gena zametne linije divljeg tipa.
9. Genetski modificirani glodavac prema patentnom zahtjevu 8, naznačen time, što:
(I) humana nepreuređena sekvenca nukleinske kiseline varijabilne regije imunoglobulinskog teškog lanca je operativno povezana s glodarskom sekvencom nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca, opcionalno naznačeno time, što je glodarska sekvenca nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca operativno povezana s humanom nepreuređenom sekvencom nukleinske kiseline varijabilne regije imunoglobulinskog teškog lanca na endogenom glodarskom lokusu imunoglobulina; i/ili
(II) naznačen time, što je glodarska sekvenca nukleinske kiseline konstantne regije imunoglobulinskog lakog lanca operativno povezana s humanom nepreuređenom sekvencom nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca na endogenom glodarskom lokusu imunoglobulina u zametnoj liniji glodavca.
10. Genetski modificirani glodavac prema patentnom zahtjevu 8 ili 9, naznačen time, što nepreuređena sekvenca nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca sadrži najviše dva humana segmenta gena VL, naznačene time, što svaki od najviše dva humana segmenta gena VL sadrži supstituciju najmanje jednog nehistidinskog ostatka histidinskim ostatkom.
11. Genetski modificirani glodavac, koji sadrži
humanu nepreuređenu sekvencu varijabilne regije imunoglobulinskog teškog lanca koja sadrži humane nepreuređene segmente VH, D i JH, naznačeno time, što je humana nepreuređena sekvenca varijabilne regije imunoglobulinskog teškog lanca operativno povezana sa sekvencom gena konstantne regije imunoglobulinskog teškog lanca, naznačeno time, što jedan ili više humanih segmenata gena VH, D i JH sadrže najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom i/ili najmanje jedno umetanje histidinskog kodona, u sekvenci nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR), naznačeno time, što supstituirani ili umetnuti histidinski kodon nije šifriran odgovarajućim humanim segmentom gena zametne linije divljeg tipa; i
jednu preuređenu humanu sekvencu nukleinske kiseline varijabilne regije VJ imunoglobulinskog lakog lanca koja sadrži humane segmente VL i JL, naznačeno time, što je jedna preuređena humana sekvenca nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca operativno povezana sa sekvencom gena konstantne regije imunoglobulinskog lakog lanca, naznačeno time, što preuređena sekvenca VJ sadrži najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom ili najmanje jedno umetanje histidinskog kodona, u sekvenci nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR), naznačeno time, što histidinski kodon humane preuređene sekvence nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca nije šifriran odgovarajućim humanim segmentom gena zametne linije divljeg tipa.
12. Genetski modificirani glodavac prema patentnom zahtjevu 11, naznačen time, što:
(I) humana nepreuređena sekvenca nukleinske kiseline varijabilne regije imunoglobulinskog teškog lanca je operativno povezana sa glodarskom sekvencom nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca, opcionalno naznačeno time, što je glodarska sekvenca nukleinske kiseline konstantne regije imunoglobulinskog teškog lanca operativno povezana s humanom nepreuređenom sekvencom nukleinske kiseline varijabilne regije imunoglobulinskog teškog lanca na endogenom glodarskom lokusu imunoglobulina u zametnoj liniji glodavca i/ili
(II) naznačen time, što je glodarska sekvenca konstantne regije imunoglobulinskog lakog lanca operativno povezana s humanom preuređenom sekvencom nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca na endogenom glodarskom lokusu imunoglobulina u zametnoj liniji glodavca.
13. Genetski modificirani glodavac, naznačen time, što životinja u svojoj zametnoj liniji sadrži
najmanje jedno umetanje histidinskog kodona ili najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom u nepreuređenoj sekvenci gena varijabilne regije imunoglobulinskog teškog lanca koja je operativno povezana s genom konstantne regije teškog lanca na lokusu imunoglobulinskog teškog lanca, naznačeno time, što je histidinski kodon lokusa imunoglobulinskog teškog lanca sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim segmentom gena zametne linije divljeg tipa; i
najmanje jedno umetanje histidinskog kodona ili najmanje jedna supstitucija nehistidinskog kodona histidinskim kodonom u nepreuređenu sekvencu gena varijabilne regije imunoglobulinskog lakog lanca koja je operativno povezana s genom konstantne regije lakog lanca na lokusu imunoglobulinskog lokusa, naznačeno time, što je histidinski kodon lokusa imunoglobulinskog lakog lanca sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim segmentom gena zametne linije divljeg tipa.
14. Metoda za dobivanje glodavca koji proizvodi varijabilne domene antitijela s histidinima šifriranim modificiranim histidinskim kodonima, koja se sastoji od:
modificiranja zametne linije glodavca kako bi sadržavala najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom ili najmanje jedno umetanje histidinskog kodona u nepreuređenu humanu sekvencu gena varijabilne regije imunoglobulinskog teškog lanca koja sadrži nepreuređene humane segmente VH, D i JH, naznačeno time, što je histidinski kodon sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim humanim segmentom gena zametne linije divljeg tipa; i/ili
modificiranja zametne linije glodavca kako bi sadržavala najmanje jednu supstituciju nehistidinskog kodona histidinskim kodonom ili najmanje jedno umetanje histidinskog kodona, u nepreuređenu humanu sekvencu gena varijabilne regije imunoglobulinskog lakog lanca koja sadrži nepreuređene humane segmente VL i JL, naznačeno time, što je histidinski kodon sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim humanim segmentom gena zametne linije divljeg tipa.
15. Metoda prema patentnom zahtjevu 14, naznačena time, što se metoda sastoji od:
(I) genetskog modificiranja zametne linije glodavca kako bi sadržavala humanu nepreuređenu sekvencu varijabilne regije imunoglobulinskog teškog lanca koja sadrži humane segmente VH, D i JH i provedbe supstitucije ili umetanja histidina u nepreuređene humane segmente VH, D i JH; i/ili
(II) genetskog modificiranja zametne linije glodavca kako bi sadržavala humanu nepreuređenu sekvencu nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca koja sadrži humane segmente VL i JL i provedbe supstitucije ili umetanja histidina u nepreuređenu humanu sekvencu nukleinske kiseline varijabilne regije imunoglobulinskog lakog lanca.
16. Metoda za dobivanje glodavca koji proizvodi varijabilne domene antitijela s histidinom šifriranim modificiranim histidinskim kodonima, koja se sastoji od:
modificiranja glodavca kako bi sadržavao najmanje jednu supstituciju histidinskog kodona nehistidinskim kodonom ili najmanje jedno umetanje histidinskog kodona u nepreuređenu sekvencu gena varijabilne regije imunoglobulinskog teškog lanca nepreuređenog varijabilnog lokusa imunoglobulinskog teškog lanca koji sadrži segmente VH, D i JH,
naznačena time, što je histidinski kodon sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim humanim segmentom gena zametne linije divljeg tipa; i
modificiranja glodavca kako bi sadržavao najmanje jednu supstituciju histidinskog kodona nehistidinskim kodonom ili najmanje jedno umetanje histidinskog kodona u jednu preuređenu varijabilnu sekvencu imunoglobulinskog lakog lanca koja sadrži preuređene sekvence segmenata VL i JL u zametnoj liniji, naznačeno time, što je histidinski kodon sekvenca nukleinske kiseline koja šifrira regiju koja određuje komplementarnost (CDR) i nije šifrirana odgovarajućim segmentom gena zametne linije divljeg tipa.
17. Glodavac prema bilo kojem patentnom zahtjevu od 1 do 13 ili dobiven pomoću metode prema bilo kojem patentnom zahtjevu od 14 do 16, naznačen time, što je glodavac odabran iz miša, štakora ili hrčka.
18. Metoda za proizvodnju antitijela koje ispoljava vezivanje za interesni antigen ovisno o pH vrijednosti koja se sastoji od imunizacije glodavca prema bilo kojem patentnom zahtjevu od 1 do 13 ili dobivenog pomoću metode prema bilo kojem patentnom zahtjevu od 14 do 16 s interesnim antigenom i odabira antitijela koje se vezuje za interesni antigen pri neutralnoj pH vrijednosti uz ispoljavanje smanjenog vezivanja za antigen pri kiseloj pH vrijednosti.
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| EP13714127.1A EP2825037B1 (en) | 2012-03-16 | 2013-03-15 | Rodents expressing ph-sensitive immunoglobulin sequences |
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Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
| MX369784B (es) | 2007-09-26 | 2019-11-21 | Chugai Pharmaceutical Co Ltd | Metodo de modificacion del punto isoelectrico de anticuerpos mediante la sustitucion de aminoacidos en region de determinacion de complementariedad (cdr). |
| DK2708559T3 (en) | 2008-04-11 | 2018-06-14 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of repeatedly binding two or more antigen molecules |
| CN108715614A (zh) | 2010-11-30 | 2018-10-30 | 中外制药株式会社 | 与多分子的抗原重复结合的抗原结合分子 |
| BR112013021526B1 (pt) | 2011-02-25 | 2021-09-21 | Chugai Seiyaku Kabushiki Kaisha | Polipeptídio variante, métodos para manter ou diminuir as atividades de ligação a fcgriia (tipo r) e fcgriia (tipo h) e aumentar a atividade de ligação a fcgriib de um polipeptídio e para a supressão da produção de um anticorpo contra um polipeptídio compreendendo a região fc do anticorpo, métodos para a produção do referido polipeptídio com atividades de ligação mantidas ou diminuídas e aumentada e para a produção suprimida de um anticorpo, composição farmacêutica e uso de um polipeptídio |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| BR112014013081A2 (pt) | 2011-11-30 | 2020-10-20 | Chugai Seiyaku Kabushiki Kaisha | veículo contendo fármaco em célula para formação de um complexo imune |
| US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
| EP2883449B1 (en) | 2012-03-16 | 2018-02-07 | Regeneron Pharmaceuticals, Inc. | Histidine engineered light chain antibodies and genetically modified rodents for generating the same |
| US9301510B2 (en) * | 2012-03-16 | 2016-04-05 | Regeneron Pharmaceuticals, Inc. | Mice that produce antigen-binding proteins with pH-dependent binding characteristics |
| BR112014022855A2 (pt) | 2012-03-16 | 2017-07-18 | Regeneron Pharma | animal não humano geneticamente modificado, mamífero geneticamente modificado, e, método para fabricar um animal não humano |
| CA2881679C (en) | 2012-08-13 | 2021-01-26 | Regeneron Pharmaceuticals, Inc. | Anti-pcsk9 antibodies with ph-dependent binding characteristics |
| CA2882272C (en) | 2012-08-24 | 2023-08-29 | Chugai Seiyaku Kabushiki Kaisha | Fc.gamma.riib-specific fc region variant |
| ES2876009T3 (es) | 2012-12-27 | 2021-11-11 | Chugai Pharmaceutical Co Ltd | Polipéptido heterodimerizado |
| DK2840892T3 (en) * | 2013-02-20 | 2018-07-23 | Regeneron Pharma | Non-human animals with modified heavy chain immunoglobulin sequences |
| AU2014250434B2 (en) | 2013-04-02 | 2019-08-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
| US9738702B2 (en) * | 2014-03-14 | 2017-08-22 | Janssen Biotech, Inc. | Antibodies with improved half-life in ferrets |
| JP6227191B1 (ja) | 2014-12-19 | 2017-11-08 | 中外製薬株式会社 | 抗ミオスタチン抗体、変異Ｆｃ領域を含むポリペプチド、および使用方法 |
| LT3233921T (lt) | 2014-12-19 | 2021-12-10 | Chugai Seiyaku Kabushiki Kaisha | Anti-c5 antikūnai ir panaudojimo būdai |
| EP3247723A1 (en) * | 2015-01-22 | 2017-11-29 | Chugai Seiyaku Kabushiki Kaisha | A combination of two or more anti-c5 antibodies and methods of use |
| KR102605798B1 (ko) | 2015-02-05 | 2023-11-23 | 추가이 세이야쿠 가부시키가이샤 | 이온 농도 의존적 항원 결합 도메인을 포함하는 항체, Fc 영역 개변체, IL-8에 결합하는 항체, 및 그들의 사용 |
| EP3271403A1 (en) * | 2015-03-19 | 2018-01-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| WO2016179518A2 (en) | 2015-05-06 | 2016-11-10 | Janssen Biotech, Inc. | Prostate specific membrane antigen (psma) bispecific binding agents and uses thereof |
| JP7141336B2 (ja) | 2015-12-25 | 2022-09-22 | 中外製薬株式会社 | 抗ミオスタチン抗体および使用方法 |
| MX2018008701A (es) * | 2016-01-13 | 2019-06-06 | Regeneron Pharma | Roedores que tienen una region de diversidad de cadena pesada modificada geneticamente. |
| EP3457840B1 (en) | 2016-05-20 | 2024-04-10 | Regeneron Pharmaceuticals, Inc. | Methods for breaking immunological tolerance using multiple guide rnas |
| CN113907043B (zh) | 2016-06-03 | 2023-08-01 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
| JP6527643B2 (ja) | 2016-08-05 | 2019-06-05 | 中外製薬株式会社 | Ｉｌ−８関連疾患の治療用又は予防用組成物 |
| WO2019190922A1 (en) | 2018-03-24 | 2019-10-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals for generating therapeutic antibodies against peptide-mhc complexes, methods of making and uses thereof |
| AU2019242586A1 (en) | 2018-03-26 | 2020-10-01 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| BR112020018691A2 (pt) * | 2018-03-26 | 2021-01-05 | Regeneron Pharmaceuticals, Inc. | Anticorpos anti-pfrh5 e fragmentos de ligação ao antígeno dos mesmos |
| CN108486126A (zh) * | 2018-03-27 | 2018-09-04 | 重庆金迈博生物科技有限公司 | 一种核酸分子及其在人源化抗体中的应用 |
| SI3629720T1 (sl) | 2018-06-14 | 2022-04-29 | Regeneron Pharmaceuticals, Inc. | Nehumane živali zmožne prerazporeditve DH-DH v kodirnih zaporedjih težke verige imunoglobulina |
| EP4211155A1 (en) | 2020-09-11 | 2023-07-19 | Regeneron Pharmaceuticals, Inc. | Identification and production of antigen-specific antibodies |
| EP4262373A1 (en) | 2020-12-16 | 2023-10-25 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized fc alpha receptors |
| US20220195014A1 (en) | 2020-12-23 | 2022-06-23 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses thereof |
| WO2024056044A1 (en) * | 2022-09-16 | 2024-03-21 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals and methods for producing heavy-chain antibodies |
Family Cites Families (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| DE69130561T2 (de) | 1990-02-16 | 1999-06-24 | Boston Biomed Res Inst | Hybride Reagenzien mit der Fähigkeit, Moleküle selektiv in Zellen freizusetzen |
| US6255458B1 (en) * | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5667988A (en) | 1992-01-27 | 1997-09-16 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| US7067284B1 (en) | 1992-01-27 | 2006-06-27 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| NZ255101A (en) | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| US5999908A (en) | 1992-08-06 | 1999-12-07 | Abelow; Daniel H. | Customer-based product design module |
| CA2219486A1 (en) * | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| JP2007312792A (ja) | 1995-08-29 | 2007-12-06 | Kirin Pharma Co Ltd | キメラ動物およびその作製法 |
| CN101333516A (zh) | 1995-08-29 | 2008-12-31 | 麒麟医药株式会社 | 嵌合体动物及其制备方法 |
| CZ294425B6 (cs) | 1997-04-14 | 2005-01-12 | Micromet Ag | Způsob výroby anti-humánního antigenového receptoru, anti-humánní antigenový receptor, řetězec VH a VL, souprava pro selekci anti-humánních antigenových receptorů a farmaceutická kompozice, obsahující uvedený receptor |
| ES2246069T3 (es) | 1997-05-02 | 2006-02-01 | Genentech, Inc. | Procedimiento de preparacion de anticuerpos multiespecificos que tienen componentes comunes y multimericos. |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6774279B2 (en) | 1997-05-30 | 2004-08-10 | Carnegie Institution Of Washington | Use of FLP recombinase in mice |
| CA2305712A1 (en) | 1997-10-03 | 1999-04-15 | Chugai Seiyaku Kabushiki Kaisha | Natural humanized antibody |
| GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
| WO2002020767A2 (en) | 2000-09-08 | 2002-03-14 | Massachusetts Institute Of Technology | G-csf analog compositions and methods |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
| WO2003031656A1 (en) | 2001-10-05 | 2003-04-17 | United States Environmental Protection Agency | Genetic testing for male factor infertility |
| US7435871B2 (en) | 2001-11-30 | 2008-10-14 | Amgen Fremont Inc. | Transgenic animals bearing human Igλ light chain genes |
| EP1512015B1 (en) | 2002-06-12 | 2009-03-25 | Genencor International, Inc. | Methods for improving a binding characteristic of a molecule |
| US20060141456A1 (en) | 2002-06-12 | 2006-06-29 | Cynthia Edwards | Methods and compositions for milieu-dependent binding of a targeted agent to a target |
| CA2872136C (en) | 2002-07-18 | 2017-06-20 | Merus B.V. | Recombinant production of mixtures of antibodies |
| EP1439234A1 (en) | 2003-01-08 | 2004-07-21 | ARTEMIS Pharmaceuticals GmbH | Targeted transgenesis using the rosa26 locus |
| DE602004021095D1 (de) | 2003-01-21 | 2009-06-25 | Chugai Pharmaceutical Co Ltd | Verfahren zum screening der leichten kette eines antikörpers |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| CA2527694C (en) | 2003-05-30 | 2015-07-14 | Hendricus Renerus Jacobus Mattheus Hoogenboom | Fab library for the preparation of anti vegf and anti rabies virus fabs |
| WO2005007696A2 (en) | 2003-07-15 | 2005-01-27 | Therapeutic Human Polyclonals, Inc. | Humanized immunoglobulin loci |
| CN1560081A (zh) | 2004-02-17 | 2005-01-05 | 大连帝恩生物工程有限公司 | 用能产生人IgGl重链－κ轻链小鼠作为制备人源化单克隆抗体和应用 |
| EP1737890A2 (en) | 2004-03-24 | 2007-01-03 | Xencor, Inc. | Immunoglobulin variants outside the fc region |
| US20050260711A1 (en) | 2004-03-30 | 2005-11-24 | Deepshikha Datta | Modulating pH-sensitive binding using non-natural amino acids |
| CN101724071A (zh) * | 2004-10-08 | 2010-06-09 | 杜门蒂斯有限公司 | 抗肿瘤坏死因子受体1的单域抗体及其使用方法 |
| DK2767161T3 (en) | 2004-10-19 | 2018-05-07 | Regeneron Pharma | Method of generating an animal homozygous for genetic modification |
| KR20070090890A (ko) | 2004-10-22 | 2007-09-06 | 메디뮨 인코포레이티드 | Ｈｍｇｂ1에 대한 고 친화성 항체 및 이의 사용 방법 |
| RU2290442C2 (ru) * | 2005-03-21 | 2006-12-27 | Всероссийский государственный научно-исследовательский институт животноводства (ВИЖ) | Способ трансформации стволовых клеток семенников животных in vivo |
| PL1861116T3 (pl) * | 2005-03-25 | 2016-02-29 | Regeneron Pharma | Formulacje antagonistów VEGF |
| JP2008538912A (ja) | 2005-04-29 | 2008-11-13 | イナート・ファルマ | 遺伝子導入動物および組換え抗体の製造方法 |
| JP2009518320A (ja) | 2005-12-05 | 2009-05-07 | シュムフォウエン アクティーゼルスカブ | 抗オルトポックスウイルス組換えポリクローナル抗体 |
| WO2007117410A2 (en) | 2006-03-31 | 2007-10-18 | Medarex, Inc. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| MX2008014804A (es) | 2006-06-02 | 2009-01-27 | Regeneron Pharma | Anticuerpos de afinidad elevada a receptor de il-6 humano. |
| CN101522716B (zh) | 2006-10-02 | 2013-03-20 | 瑞泽恩制药公司 | 抗人il-4受体的高亲和力人抗体 |
| US7608693B2 (en) | 2006-10-02 | 2009-10-27 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human IL-4 receptor |
| AU2007306340A1 (en) * | 2006-10-11 | 2008-04-17 | Ablynx N.V. | Amino acid sequences that bind to serum proteins in a manner that is essentially independent of the pH, compounds comprising the same, and use thereof |
| US20100034194A1 (en) | 2006-10-11 | 2010-02-11 | Siemens Communications Inc. | Eliminating unreachable subscribers in voice-over-ip networks |
| RU2448979C2 (ru) | 2006-12-14 | 2012-04-27 | Ридженерон Фармасьютикалз, Инк. | Антитела человека к дельта-подобному лиганду-4 человека |
| KR20090130236A (ko) | 2007-03-13 | 2009-12-21 | 내셔날 쥬이쉬 헬스 | 항체의 제조 방법 |
| ITMI20071522A1 (it) | 2007-07-27 | 2009-01-28 | Areta Internat S R L | Vaccino idiotipico |
| CA2697193C (en) | 2007-09-14 | 2017-06-06 | Adimab, Inc. | Rationally designed, synthetic antibody libraries and uses therefor |
| MX369784B (es) | 2007-09-26 | 2019-11-21 | Chugai Pharmaceutical Co Ltd | Metodo de modificacion del punto isoelectrico de anticuerpos mediante la sustitucion de aminoacidos en region de determinacion de complementariedad (cdr). |
| WO2009055669A2 (en) * | 2007-10-26 | 2009-04-30 | Oklahoma Medical Research Foundation | Monoclonal antibodies against activated and unactivated protein c |
| ES2483942T5 (es) | 2007-12-14 | 2017-02-06 | Novo Nordisk A/S | Anticuerpos contra NKG2D humano y usos de los mismos |
| CA2718495C (en) * | 2008-03-14 | 2022-06-14 | Humanzyme Limited | Recombinant production of authentic human proteins using human cell expression systems |
| DK2708559T3 (en) | 2008-04-11 | 2018-06-14 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of repeatedly binding two or more antigen molecules |
| AU2009263082C1 (en) | 2008-06-27 | 2018-11-01 | Merus N.V. | Antibody producing non-human mammals |
| TWI516501B (zh) | 2008-09-12 | 2016-01-11 | 禮納特神經系統科學公司 | Ｐｃｓｋ９拮抗劑類 |
| TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
| AU2009298458B2 (en) | 2008-09-30 | 2015-10-08 | Ablexis, Llc | Non-human mammals for the production of chimeric antibodies |
| EP2196476A1 (en) * | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| AU2009329365B2 (en) | 2008-12-18 | 2016-01-14 | Roger Kingdon Craig | Non-human transgenic animals expressing humanised antibodies and use thereof |
| US8808136B2 (en) | 2009-05-07 | 2014-08-19 | Volvo Construction Equipment Ab | Working machine and a method for operating a working machine |
| JP5804521B2 (ja) | 2009-05-29 | 2015-11-04 | モルフォシス・アー・ゲー | コレクション及びその使用方法 |
| CN102471378B (zh) | 2009-06-26 | 2014-04-02 | 瑞泽恩制药公司 | 容易地分离的具有天然免疫球蛋白形式的双特异性抗体 |
| HUE055817T2 (hu) | 2009-07-08 | 2021-12-28 | Kymab Ltd | Állatmodellek és terápiás molekulák |
| US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
| EP2454277B1 (en) | 2009-07-16 | 2017-12-13 | Wageningen Universiteit | Regulation of zinc deficiency and tolerance in plants |
| GB2472108B (en) | 2009-08-27 | 2011-07-13 | Budha Singh Dhinjan | Wall bead |
| LT2954779T (lt) | 2009-12-10 | 2019-05-27 | Regeneron Pharmaceuticals, Inc. | Pelės, gaminančios sunkiosios grandinės antikūnus |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20130185821A1 (en) | 2010-02-08 | 2013-07-18 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| SI3095871T1 (sl) | 2010-02-08 | 2019-06-28 | Regeneron Pharmaceuticals, Inc. | Miš z navadno lahko verigo |
| SA111320266B1 (ar) | 2010-03-11 | 2015-06-21 | رينات نيوروساينس كوربوريشن | أجسام مضادة مع ارتباط مولد مضاد يعتمد على الأس الهيدروجيني |
| TWI667346B (zh) | 2010-03-30 | 2019-08-01 | 中外製藥股份有限公司 | 促進抗原消失之具有經修飾的FcRn親和力之抗體 |
| CN103228130B (zh) | 2010-06-17 | 2016-03-16 | 科马布有限公司 | 动物模型及治疗分子 |
| IL300712A (en) | 2010-06-22 | 2023-04-01 | Regeneron Pharma | Mice with light chain to human |
| PL2550363T3 (pl) | 2011-02-25 | 2015-05-29 | Regeneron Pharma | Myszy adam6 |
| RS61946B1 (sr) | 2011-08-05 | 2021-07-30 | Regeneron Pharma | Humanizovani miševi univerzalnog lakog lakca |
| US10024867B2 (en) | 2011-09-30 | 2018-07-17 | Chugai Seiyaku Kabushiki Kaisha | Ion concentration-dependent binding molecule library |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| KR20140136462A (ko) | 2012-03-06 | 2014-11-28 | 리제너론 파마슈티칼스 인코포레이티드 | 공통 경쇄 마우스 |
| BR112014022855A2 (pt) | 2012-03-16 | 2017-07-18 | Regeneron Pharma | animal não humano geneticamente modificado, mamífero geneticamente modificado, e, método para fabricar um animal não humano |
| EP2883449B1 (en) | 2012-03-16 | 2018-02-07 | Regeneron Pharmaceuticals, Inc. | Histidine engineered light chain antibodies and genetically modified rodents for generating the same |
| US9301510B2 (en) | 2012-03-16 | 2016-04-05 | Regeneron Pharmaceuticals, Inc. | Mice that produce antigen-binding proteins with pH-dependent binding characteristics |
| US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
| SG10201609535TA (en) | 2012-06-05 | 2017-01-27 | Regeneron Pharma | Methods for making fully human bispecific antibodies using a common light chain |
| EP2898116A4 (en) | 2012-09-21 | 2016-06-01 | Reoxcyn Discoveries Group Inc | CELL FOR ELECTROLYSING A LIQUID |
| DK2840892T3 (en) | 2013-02-20 | 2018-07-23 | Regeneron Pharma | Non-human animals with modified heavy chain immunoglobulin sequences |
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