DK2883449T3 - Histidinmanipulerede letkædeantistoffer og genetisk modificerede gnavere til generering heraf - Google Patents

Histidinmanipulerede letkædeantistoffer og genetisk modificerede gnavere til generering heraf Download PDF

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DK2883449T3
DK2883449T3 DK15151655.6T DK15151655T DK2883449T3 DK 2883449 T3 DK2883449 T3 DK 2883449T3 DK 15151655 T DK15151655 T DK 15151655T DK 2883449 T3 DK2883449 T3 DK 2883449T3
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Denmark
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light chain
human
immunoglobulin
sequence
histidine
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DK15151655.6T
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English (en)
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John Mcwhirter
Lynn Macdonald
Andrew J Murphy
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Regeneron Pharma
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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
    • 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
    • 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
    • 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
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • 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
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • 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
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • 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
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • 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
    • 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
    • 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
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC

Claims (14)

1. Genetisk modificeret gnaver, der i sin kimbane omfatter et immunoglobulin-letkædelocus, der omfatter (i) en enkelt omarrangeret human immunoglobulin-letkæde-variabel-region-gensekvens, der omfatter humane VL- og JL-segmentsekvenser, og (ii) en immunoglobulin-letkæde-konstant-region-gensekvens i operabel binding til den enkelte omarrangerede humane immunoglobulin-letkæde-variabel-region-gensekvens, hvor den enkelte omarrangerede humane immunoglobulin-letkæde- variabel-region-gensekvens omfatter mindst én genetisk manipuleret indsætning eller substitution af en histidincodon, der ikke er kodet for af tilsvarende VL- og JL-gensekvenser fra human kimbane, hvor den enkelte omarrangerede humane immunoglobulin-letkæde- variabel-region-gensekvens koder for en immunoglobulinkæde, der omfatter et variabelt letkædedomæne, hvor histidincodonen er i nukleotidsekvensen, der koder for en komplementaritetsbestemmende region (CDR) af det variable letkædedomæne, hvor det variable letkædedomæne omfatter mindst én histidinrest ved en aminosyreposition, der er kodet for af mindst den ene indsatte eller substituerede histidincodon, og hvor immunoglobulin-letkæden kodet for af immunoglobulin-letkædelocusset kan parres med en flerhed af tunge immunoglobulinkæder udvalgt fra gnaveren, hvor hver af flerheden af tunge immunoglobulinkæder specifikt binder forskellige epitoper ved parring med immunoglobulin-letkæden.
2. Gnaver ifølge krav 1, hvor flerheden af tunge immunoglobulinkæder omfatter somatiske mutationer.
3. Gnaver ifølge krav 1, hvor: immunoglobulin-letkæde-konstant-region-gensekvensen er en ikke-human immunoglobulin-letkæde-konstant-region-gensekvens, såsom en endogen ikke-human immunoglobulin-letkæde-konstant-region-gensekvens, hvor immunoglobulin-letkædelocusset eventuelt er ved et endogent ikke-humant immunoglobulin-letkædelocus.
4. Gnaver ifølge et hvilket som helst af de foregående krav, hvor: gnaveren endvidere i sin kimbane omfatter et immunoglobulin- tungkædelocus, der omfatter en ikke-omarrangeret immunoglobulin-tungkæde-variabel-region-gensekvens, der omfatter humane VH-, DH- og JH-segmenter operativt forbundet med en immunoglobulin-tungkæde-konstant-region-gensekvens, eventuelt hvor immunoglobulin-tungkæde-konstant-region-gensekvensen er en ikke-human immunoglobulin-tungkæde-konstant-region-gensekvens, såsom en endogen, ikke-human immunoglobulin-konstant-region-gensekvens, hvor immunoglobulin-tungkædelocusset eventuelt er ved et endogent ikke-humant immunoglobulin-tungkædelocus.
5. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren mangler en funktionel ikke-omarrangeret immunoglobulin-letkæde-variabel-region.
6. Gnaver ifølge et hvilket som helst af de foregående krav, hvor den genetisk manipulerede indsætning eller substitution af histidincodon er i nukleotidsekvensen, der koder for en komplementaritetsbestemmende region (CDR) 3, eventuelt hvor histidincodonen er én, to, tre eller fire CDR3-codoner.
7. Gnaver ifølge et hvilket som helst af de foregående krav, hvor den enkelte omarrangerede humane variable immunoglobulin-letkæderegion er afledt af et humant Vk1-39- eller VK3-20-gensegment, eventuelt hvor den enkelte omarrangerede humane variable immunoglobulin-letkæderegion er afledt af en omarrangeret Vk1-39/Jk5- eller Vk3-20/Jk1-gensekvens.
8. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren omfatter en population af B-celler som reaktion på et antigen af interesse, der er beriget med antistoffer, der udviser et fald i dissociationshalveringstid (t 1/2) ved et surt pH sammenlignet med neutralt pH på mindst ca. 2-fold, mindst ca. 3-fold, mindst ca. 4-fold, mindst ca. 5-fold, mindst ca. 10-fold, mindst ca. 15-fold, mindst ca. 20-fold, mindst ca. 25-fold, mindst ca. 30-fold eller eventuelt ca. 30-fold eller mere.
9. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren udtrykker et antistof, der omfatter et humant variabelt immunoglobulin-letkædedomæne med en substitution af mindst én ikke-histidinrest med en histidinrest ved en aminosyreposition kodet for af den genetisk manipulerede histidincodon i den enkelte omarrangerede immunoglobulin-letkæde-variabel-region-gensekvens, der ikke er kodet for af VL- og JL-gensekvenser fra human kimbane.
10. Gnaver ifølge et hvilket som helst af de foregående krav, hvor den enkelte omarrangerede humane immunoglobulin-letkæde-variabel-region-gensekvens erstatter en endogen ikke-omarrangeret letkæde-variabel-region-gensekvens.
11. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren er en rotte.
12. Gnaver ifølge et hvilket som helst af kravene 1 til 10, hvor gnaveren er en mus.
13. Gnaver ifølge et hvilket som helst af de foregående krav, hvor den enkelte omarrangerede humane immunoglobulin-letkæde-variabel-region-gensekvens er operativt forbundet med en immunoglobulin-letkæde-konstant-region-gensekvens udvalgt fra en rotte- eller en muse- immunoglobulin-letkæde-konstant-region-gensekvens, hvor immunoglobulin-letkædelocusset eventuelt er ved et endogent muse-letkædelocus; og hvor gnaveren eventuelt endvidere i sin kimbane omfatter et immunoglobulin-tungkædelocus, der omfatter en ikke-omarrangeret immunoglobulin-tungkæde-variabel-region-sekvens, der omfatter humane VH-, DH- og JH-segmenter operativt forbundet med en immunoglobulin-tungkæde-konstant-region-gensekvens udvalgt fra en rotte- eller en muse-tungkæde-konstant-region-gensekvens; hvor immunoglobulin-tungkædelocusset eventuelt er ved et endogent muse-immunoglobulin-tungkædelocus.
14. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren udtrykker en population af antigenspecifikke antistoffer som reaktion på et antigen af interesse, hvor samtlige af populationens antistoffer omfatter: variable immunoglobulin-letkædedomæner afledt af den samme enkelte omarrangerede humane letkæde-variabel-region-gensekvens, der omfatter humane VL- og JL-segmentsekvenser, der omfatter mindst én genetisk manipuleret histidincodon, der ikke er kodet for af tilsvarende VL- og JL-gensekvenser fra human kimbane, og immunoglobulin-tungkæder, der omfatter humane variable tungkædedomæner afledt af et repertoire af humane V-, D- og J-tungkædesegmenter.
DK15151655.6T 2012-03-16 2013-03-15 Histidinmanipulerede letkædeantistoffer og genetisk modificerede gnavere til generering heraf DK2883449T3 (da)

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US201261611950P 2012-03-16 2012-03-16
US201261736930P 2012-12-13 2012-12-13
EP13713652.9A EP2825036B1 (en) 2012-03-16 2013-03-15 Histidine engineered light chain antibodies and genetically modified rodents for generating the same

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US (3) US9334334B2 (da)
EP (4) EP3808175A1 (da)
JP (5) JP6185978B2 (da)
KR (1) KR102228296B1 (da)
CN (3) CN104302169B (da)
AU (3) AU2013204579B2 (da)
BR (1) BR112014022850A2 (da)
CA (1) CA2865643A1 (da)
CY (2) CY1120599T1 (da)
DK (2) DK2825036T3 (da)
ES (3) ES2665793T3 (da)
HK (2) HK1200273A1 (da)
HR (2) HRP20180682T1 (da)
HU (3) HUE053310T2 (da)
IL (5) IL234355B (da)
LT (3) LT2825036T (da)
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NZ (1) NZ629639A (da)
PL (2) PL2825036T3 (da)
PT (3) PT3348140T (da)
RS (2) RS57118B1 (da)
RU (2) RU2017135754A (da)
SG (2) SG11201405165UA (da)
SI (3) SI3348140T1 (da)
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Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2568436T3 (es) 2006-03-31 2016-04-29 Chugai Seiyaku Kabushiki Kaisha Procedimiento para controlar la farmacocinética en sangre de anticuerpos
EP3689912A1 (en) 2007-09-26 2020-08-05 Chugai Seiyaku Kabushiki Kaisha Method of modifying isoelectric point of antibody via amino acid substitution in cdr
EP4238993A3 (en) 2008-04-11 2023-11-29 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly
SG190727A1 (en) 2010-11-30 2013-07-31 Chugai Pharmaceutical Co Ltd Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly
KR102147548B1 (ko) 2011-02-25 2020-08-24 추가이 세이야쿠 가부시키가이샤 ＦｃγＲＩＩｂ 특이적 Ｆｃ 항체
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
RU2603090C2 (ru) 2011-10-17 2016-11-20 Регенерон Фармасьютикалс, Инк. Мыши с ограниченной тяжелой цепью иммуноглобулина
EP3517550A1 (en) 2011-11-30 2019-07-31 Chugai Seiyaku Kabushiki Kaisha Drug containing carrier into cell for forming immune complex
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
RS59076B1 (sr) 2012-03-16 2019-09-30 Regeneron Pharma Glodari koji eksprimiraju imunoglobulinske sekvence senzitivne na ph
LT3597037T (lt) 2012-06-12 2021-06-10 Regeneron Pharmaceuticals, Inc. Humanizuoti gyvūnai, išskyrus žmones, su apribotu imunoglobulino sunkiosios grandinės lokusu
TWI697501B (zh) 2012-08-24 2020-07-01 日商中外製藥股份有限公司 ＦｃγＲＩＩｂ特異性Ｆｃ區域變異體
JP6774164B2 (ja) 2012-08-24 2020-10-21 中外製薬株式会社 マウスＦｃγＲＩＩ特異的Ｆｃ抗体
CN105102618B (zh) 2012-12-27 2018-04-17 中外制药株式会社 异源二聚化多肽
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
WO2014163101A1 (ja) 2013-04-02 2014-10-09 中外製薬株式会社 Ｆｃ領域改変体
PE20190920A1 (es) 2013-04-29 2019-06-26 Hoffmann La Roche Anticuerpos modificados de union a fcrn humano y metodos de utilizacion
KR20160104636A (ko) 2014-01-15 2016-09-05 에프. 호프만-라 로슈 아게 단백질 Ａ-결합이 개선된 Ｆｃ-영역 변이체
TWI681969B (zh) * 2014-01-23 2020-01-11 美商再生元醫藥公司 針對ｐｄ-１的人類抗體
TWI680138B (zh) * 2014-01-23 2019-12-21 美商再生元醫藥公司 抗ｐｄ-ｌ１之人類抗體
AU2015283270B9 (en) * 2014-06-30 2021-04-01 Merck Patent Gmbh Anti-TNFa antibodies with pH-dependent antigen binding
TWI808330B (zh) 2014-12-19 2023-07-11 日商中外製藥股份有限公司 抗肌抑素之抗體、含變異Fc區域之多胜肽及使用方法
SG11201607165YA (en) * 2014-12-19 2016-09-29 Chugai Pharmaceutical Co Ltd Anti-c5 antibodies and methods of use
CN107428823B (zh) * 2015-01-22 2021-10-26 中外制药株式会社 两种以上抗-c5抗体的组合与使用方法
TW202248212A (zh) 2015-02-05 2022-12-16 日商中外製藥股份有限公司 包含離子濃度依賴之抗原結合域的抗體、Fc區變體、IL-8結合抗體與其用途
AU2016232715A1 (en) 2015-03-19 2017-09-28 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
CN107614014B (zh) * 2015-05-28 2022-07-12 生物辐射实验室股份有限公司 亲和配体及其相关方法
EP3390442B1 (en) * 2015-12-18 2023-11-08 Chugai Seiyaku Kabushiki Kaisha Anti-c5 antibodies and methods of use
WO2017104783A1 (en) * 2015-12-18 2017-06-22 Chugai Seiyaku Kabushiki Kaisha Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use
EP3394098A4 (en) 2015-12-25 2019-11-13 Chugai Seiyaku Kabushiki Kaisha ANTI-MYOSTATIN ANTIBODIES AND METHODS OF USE
KR20240016444A (ko) 2016-05-20 2024-02-06 리제너론 파마슈티칼스 인코포레이티드 다중 가이드 RNAs를 이용한 면역학적 내성 파괴 방법
JP7053499B2 (ja) 2016-06-03 2022-04-12 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物
EP3494991A4 (en) 2016-08-05 2020-07-29 Chugai Seiyaku Kabushiki Kaisha COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATING TO IL-8
GB201707484D0 (en) * 2017-05-10 2017-06-21 Argenx Bvba Method of preparing ph-dependent antibodies
EP3765498A1 (en) * 2018-03-14 2021-01-20 F. Hoffmann-La Roche AG Method for affinity maturation of antibodies
RU2020131383A (ru) * 2018-03-24 2022-04-26 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, для выработки терапевтических антител против комплексов пептид-mhc, способы их получения и варианты применения
MA52177A (fr) 2018-03-26 2021-02-17 Regeneron Pharma Rongeurs humanisés pour tester des agents thérapeutiques
SG11202012084WA (en) 2018-06-14 2021-01-28 Regeneron Pharma Non-human animals capable of dh-dh rearrangement in the immunoglobulin heavy chain coding sequences
JP6935383B2 (ja) * 2018-09-27 2021-09-15 公益財団法人実験動物中央研究所 免疫不全マウス
JP6780155B1 (ja) 2019-04-04 2020-11-04 日精エー・エス・ビー機械株式会社 樹脂製容器の製造方法、射出コア型、射出成形用金型および樹脂製容器の製造装置
JP2022535418A (ja) 2019-06-05 2022-08-08 リジェネロン・ファーマシューティカルズ・インコーポレイテッド カッパ遺伝子座から発現される限られたラムダ軽鎖レパートリーを有する非ヒト動物及びその使用
BR112022007923A2 (pt) * 2019-10-28 2022-07-26 Regeneron Pharma Anticorpo recombinante isolado ou fragmento de ligação ao antígeno deste, composição farmacêutica, molécula de polinucleotídeo, vetor, célula, e, método para prevenir, tratar ou melhorar pelo menos um sintoma da infecção por influenza
CA3189225A1 (en) * 2020-08-04 2022-02-10 Seagen Inc. Anti-cd228 antibodies and antibody-drug conjugates
JP2023542490A (ja) 2020-09-03 2023-10-10 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｐｄ－１阻害剤を投与することによりがん疼痛を処置する方法
US20220090060A1 (en) 2020-09-11 2022-03-24 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
KR20230125236A (ko) 2020-12-23 2023-08-29 리제너론 파마슈티칼스 인코포레이티드 앵커 변형된 항체를 암호화하는 핵산 및 이의 사용

Family Cites Families (85)

* Cited by examiner, † Cited by third party
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
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
ES2108048T3 (es) 1990-08-29 1997-12-16 Genpharm Int Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos.
US7067284B1 (en) 1992-01-27 2006-06-27 The Scripps Research Institute Methods for producing antibody libraries using universal or randomized immunoglobulin light chains
US5667988A (en) 1992-01-27 1997-09-16 The Scripps Research Institute Methods for producing antibody libraries using universal or randomized immunoglobulin light chains
CA2140638C (en) 1992-07-24 2010-05-04 Raju Kucherlapati Generation of xenogeneic antibodies
US5999908A (en) 1992-08-06 1999-12-07 Abelow; Daniel H. Customer-based product design module
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES
DK0843961T3 (da) 1995-08-29 2007-05-21 Kirin Brewery Kimærisk mus og fremgangsmåde til at producere samme
CN100387621C (zh) 1997-04-14 2008-05-14 麦可麦脱股份公司 抗人抗原受体的新的生产方法及其用途
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
AU751659B2 (en) 1997-05-02 2002-08-22 Genentech Inc. A 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
CN1277632A (zh) 1997-10-03 2000-12-20 中外制药株式会社 天然人源化抗体
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
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
WO2003031656A1 (en) 2001-10-05 2003-04-17 United States Environmental Protection Agency Genetic testing for male factor infertility
US20060199204A1 (en) 2001-10-05 2006-09-07 U.S. Epa Genetic testing for male factor infertility
DK2319301T3 (da) 2001-11-30 2017-12-04 Amgen Fremont Inc Transgene dyr med humane Ig lambda let kæde gener
US20060141456A1 (en) 2002-06-12 2006-06-29 Cynthia Edwards Methods and compositions for milieu-dependent binding of a targeted agent to a target
CA2489022C (en) 2002-06-12 2012-10-16 Genencor International, Inc. Methods for improving a binding characteristic of a molecule
ES2442615T5 (es) 2002-07-18 2023-03-16 Merus Nv Producción recombinante de mezclas de anticuerpos
EP1439234A1 (en) 2003-01-08 2004-07-21 ARTEMIS Pharmaceuticals GmbH Targeted transgenesis using the rosa26 locus
US8337841B2 (en) 2003-01-21 2012-12-25 Chugai Seiyaku Kabushiki Kaisha Methods of screening for antibody light chains
EP1639009B1 (en) 2003-05-30 2013-02-27 Merus B.V. Fab library for the preparation of a mixture of antibodies
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
MXPA06000562A (es) 2003-07-15 2006-03-30 Therapeutic Human Polyclonals Loci de inmunoglobulina humanizada.
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
WO2006044962A1 (en) 2004-10-19 2006-04-27 Regeneron Pharmaceuticals, Inc. Method for generating an animal homozygous for a genetic modification
CN101132811B (zh) 2004-10-22 2012-05-30 米迪缪尼有限公司 抗hmgb1的高亲和力抗体及其用法
CA2604440A1 (en) 2005-04-29 2006-11-09 Inserm (Institut De La Sante Et De La Recherche Medicale) Transgenic animals and methods of making recombinant antibodies
US7850965B2 (en) 2005-12-05 2010-12-14 Symphogen A/S Anti-orthopoxvirus recombinant polyclonal antibody
JP5514539B2 (ja) 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
RS52643B (en) 2006-06-02 2013-06-28 Regeneron Pharmaceuticals Inc. HIGH AFINITY ANTIBODIES TO THE HUMAN IL-6 RECEPTOR
RU2445318C2 (ru) 2006-10-02 2012-03-20 Ридженерон Фармасьютикалз, Инк. Высокоаффинные антитела человека к рецептору il-4 человека
US7608693B2 (en) 2006-10-02 2009-10-27 Regeneron Pharmaceuticals, Inc. High affinity human antibodies to human IL-4 receptor
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
CA2680613A1 (en) 2007-03-13 2008-09-18 National Jewish Medical And Research Center Methods for generation of antibodies
ITMI20071522A1 (it) 2007-07-27 2009-01-28 Areta Internat S R L Vaccino idiotipico
BRPI0816785A2 (pt) 2007-09-14 2017-05-02 Adimab Inc bibliotecas de anticorpos sintéticos racionalmente desenhadas, e, usos para as mesmas
EP3689912A1 (en) 2007-09-26 2020-08-05 Chugai Seiyaku Kabushiki Kaisha Method of modifying isoelectric point of antibody via amino acid substitution in cdr
PL2222706T5 (pl) 2007-12-14 2017-09-29 Novo Nordisk As Przeciwciała przeciwko ludzkiemu NKG2D i ich zastosowania
EP4238993A3 (en) * 2008-04-11 2023-11-29 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly
AU2009246946B2 (en) * 2008-05-01 2013-09-26 Amgen Inc. Anti-hepcidin antibodies and methods of use
EP2556747B1 (en) 2008-06-27 2020-12-02 Merus N.V. Antibody producing transgenic mice
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
KR101987351B1 (ko) 2008-09-30 2019-06-10 아블렉시스, 엘엘씨 키메라 항체의 제조를 위한 인간 이외의 포유동물
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).
SG172176A1 (en) 2008-12-18 2011-07-28 Univ Erasmus Medical Ct Non-human transgenic animals expressing humanised antibodies and use therof
CN102427978B (zh) 2009-05-07 2016-01-20 沃尔沃建筑设备公司 工程机械和用于操作工程机械的方法
CN102449149B (zh) 2009-05-29 2014-04-23 莫佛塞斯公司 集合及其使用方法
PL2975051T3 (pl) 2009-06-26 2021-09-20 Regeneron Pharmaceuticals, Inc. Wyizolowane z łatwością dwuswoiste przeciwciała o formacie natywnej immunoglobuliny
US20120204278A1 (en) 2009-07-08 2012-08-09 Kymab Limited Animal models and therapeutic molecules
ES2965212T3 (es) 2009-07-08 2024-04-11 Kymab Ltd Modelos de animales y moléculas terapéuticas
ES2658622T3 (es) 2009-07-16 2018-03-12 Wageningen Universiteit Regulación de la deficiencia de zinc y tolerancia en plantas
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
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
TR201906650T4 (tr) 2010-02-08 2019-05-21 Regeneron Pharma Ortak hafif zincirli fare.
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
CN102844332B (zh) 2010-03-11 2015-08-19 瑞纳神经科学公司 呈pH依赖性抗原结合的抗体
TWI667257B (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
EP2582230A1 (en) 2010-06-17 2013-04-24 Kymab Limited Animal models and therapeutic molecules
RS58736B1 (sr) 2010-06-22 2019-06-28 Regeneron Pharma Miševi koji ispoljavaju imunoglobinski hibrid lakog lanca sa ljudskom varijabilnom regijom
DK2550363T3 (da) 2011-02-25 2015-03-23 Regeneron Pharma ADAM6-mus
ES2872081T3 (es) 2011-08-05 2021-11-02 Regeneron Pharma Ratones con cadena ligera universal humanizada
CA3186007A1 (en) 2011-09-30 2013-04-04 Chugai Seiyaku Kabushiki Kaisha Ion concentration-dependent binding molecule library
GB201122047D0 (en) 2011-12-21 2012-02-01 Kymab Ltd Transgenic animals
AU2013204140B2 (en) 2012-03-06 2016-01-28 Regeneron Pharmaceuticals, Inc. Common light chain mouse
RS59076B1 (sr) 2012-03-16 2019-09-30 Regeneron Pharma Glodari koji eksprimiraju imunoglobulinske sekvence senzitivne na ph
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
RU2014153674A (ru) 2012-06-05 2016-07-27 Регенерон Фармасьютикалз, Инк. Способ получения полностью человеческих биспецифических антител с применением общей легкой цепи
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca

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