CA2135313A1 - Methodes pour l'obtention d'animaux transgeniques, comportant un chromosome artificiel de levure - Google Patents

Methodes pour l'obtention d'animaux transgeniques, comportant un chromosome artificiel de levure

Info

Publication number: CA2135313A1
Authority: CA; Canada
Prior art keywords: gene; yac; cells; polynucleotide; human
Prior art date: 1992-06-18
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA 2135313

Other languages

English (en)

Inventor

Theodore Choi

Jeanne F. Loring

Robert M. Kay

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Genpharm International Inc

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-06-18

Filing date

1993-06-18

Publication date

1994-01-06

1993-06-18 Application filed by Individual filed Critical Individual

1994-01-06 Publication of CA2135313A1 publication Critical patent/CA2135313A1/fr

Status Abandoned legal-status Critical Current

Links

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- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal 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; AVICULTURE; APICULTURE; PISCICULTURE; 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; 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; AVICULTURE; APICULTURE; PISCICULTURE; 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0312—Animal model for Alzheimer's disease
- 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
- C07K2317/52—Constant or Fc region; Isotype

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Health & Medical Sciences (AREA)
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Genetics & Genomics (AREA)
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Organic Chemistry (AREA)
Zoology (AREA)
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Proteomics, Peptides & Aminoacids (AREA)
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CA 2135313 1992-06-18 1993-06-18 Methodes pour l'obtention d'animaux transgeniques, comportant un chromosome artificiel de levure Abandoned CA2135313A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US90097292A	1992-06-18	1992-06-18
US149393A	1993-01-07	1993-01-07
US08/001,493		1993-01-07
US07/900,972		1993-06-18

Publications (1)

Publication Number	Publication Date
CA2135313A1 true CA2135313A1 (fr)	1994-01-06

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ID=26669098

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2135313 Abandoned CA2135313A1 (fr)	1992-06-18	1993-06-18	Methodes pour l'obtention d'animaux transgeniques, comportant un chromosome artificiel de levure

Country Status (6)

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EP (1)	EP0648265A4 (fr)
JP (1)	JPH07508410A (fr)
AU (1)	AU4541093A (fr)
CA (1)	CA2135313A1 (fr)
NZ (1)	NZ253943A (fr)
WO (1)	WO1994000569A1 (fr)

Families Citing this family (238)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6150584A (en) *	1990-01-12	2000-11-21	Abgenix, Inc.	Human antibodies derived from immunized xenomice
US6075181A (en) *	1990-01-12	2000-06-13	Abgenix, Inc.	Human antibodies derived from immunized xenomice
US6673986B1 (en)	1990-01-12	2004-01-06	Abgenix, Inc.	Generation of xenogeneic antibodies
ATE356869T1 (de) *	1990-01-12	2007-04-15	Amgen Fremont Inc	Bildung von xenogenen antikörpern
US6657103B1 (en)	1990-01-12	2003-12-02	Abgenix, Inc.	Human antibodies derived from immunized xenomice
US6713610B1 (en)	1990-01-12	2004-03-30	Raju Kucherlapati	Human antibodies derived from immunized xenomice
US6610493B1 (en)	1993-06-17	2003-08-26	Brigham And Women's Hospital	Screening compounds for the ability to alter the production of amyloid-β peptide
JPH07509137A (ja) *	1992-07-24	1995-10-12	セル　ジェネシス，インク．	異種抗体の生産
WO1994023049A2 (fr) *	1993-04-02	1994-10-13	The Johns Hopkins University	Introduction et expression de grandes sequences genomiques chez des animaux transgeniques
ATE198622T1 (de)	1993-10-27	2001-01-15	Elan Pharm Inc	Transgene tiere, die app allele mit der schwedischen mutation beherbergen
FR2714830B1 (fr) *	1994-01-10	1996-03-22	Rhone Poulenc Rorer Sa	Composition contenant des acides nucléiques, préparation et utilisations.
US5777153A (en) *	1994-07-08	1998-07-07	Gilead Sciences, Inc.	Cationic lipids
FR2732895B1 (fr) *	1995-04-11	1997-05-16	Pasteur Merieux Serums Vacc	Utilisation d'un compose amphipathique cationique comme agent de transfection, comme adjuvant de vaccin, ou comme medicament
EP0822830B1 (fr) *	1995-04-27	2008-04-02	Amgen Fremont Inc.	Anticorps anti-IL-8 dérivés de xenosouris immunisées
US6531586B1 (en)	1995-04-28	2003-03-11	The Hospital For Sick Children	Genetic sequences related to Alzheimer's Disease
US5986054A (en)	1995-04-28	1999-11-16	The Hospital For Sick Children, Hsc Research And Development Limited Partnership	Genetic sequences and proteins related to alzheimer's disease
US6210919B1 (en)	1995-04-28	2001-04-03	Hsc Research And Development Limited Partnership	Genetic sequences and proteins related to alzheimer's disease
CA2223088A1 (fr)	1995-06-07	1996-12-19	Bob Dale Brown	Nouveaux lipides cationiques a base de carbamate
US6717031B2 (en)	1995-06-07	2004-04-06	Kate Dora Games	Method for selecting a transgenic mouse model of alzheimer's disease
US6632976B1 (en)	1995-08-29	2003-10-14	Kirin Beer Kabushiki Kaisha	Chimeric mice that are produced by microcell mediated chromosome transfer and that retain a human antibody gene
JP2000506375A (ja) *	1996-01-26	2000-05-30	エイチエスシーリサーチアンドデベロップメントリミテッドパートナーシップ	アルツハイマー病に関連する核酸およびタンパク質、ならびにその使用
US6093816A (en)	1996-06-27	2000-07-25	Isis Pharmaceuticals, Inc.	Cationic lipids
CA2183901A1 (fr) *	1996-08-22	1998-02-23	Johanna E. Bergmann	Cibles pour le traitement et le diagnostic de la maladie d'alzheimer et du syndrome de down chez les humains
PT1500329E (pt)	1996-12-03	2012-06-18	Amgen Fremont Inc	Anticorpos humanos que se ligam especificamente ao tnf alfa humano
US6682736B1 (en)	1998-12-23	2004-01-27	Abgenix, Inc.	Human monoclonal antibodies to CTLA-4
CN1328571B (zh)	1998-12-23	2016-08-31	辉瑞大药厂	抗ctla-4的人单克隆抗体
US7109003B2 (en)	1998-12-23	2006-09-19	Abgenix, Inc.	Methods for expressing and recovering human monoclonal antibodies to CTLA-4
US6833268B1 (en)	1999-06-10	2004-12-21	Abgenix, Inc.	Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US6900367B2 (en)	2000-09-29	2005-05-31	Novartis	Transgenic Drosophila melanogaster expressing a β42 in the eye
EP1383541A4 (fr) *	2001-03-22	2009-11-04	Chromos Molecular Systems Inc	Techniques d'apport de molecules d'acides nucleiques dans des cellules et evaluation de cet apport
MXPA03010626A (es)	2001-05-30	2004-12-06	Chromos Molecular Systems Inc	Plataformas a base de cromosomas.
JP2005518212A (ja)	2002-02-25	2005-06-23	ジェネンテック・インコーポレーテッド	新規な１型サイトカインレセプターｇｌｍ−ｒ
DE60333228D1 (de)	2002-12-02	2010-08-12	Amgen Fremont Inc	Gegen den tumor nekrose faktor gerichtete antikörper und deren verwendungen
US8110674B2 (en)	2003-03-07	2012-02-07	Alnylam Pharmaceuticals, Inc.	Therapeutic compositions
EP3000886A1 (fr)	2003-03-19	2016-03-30	Amgen Fremont Inc.	Anticorps contre l'antigene de lymphocytes t, du domaine d'immunoglobuline et du domaine 1 de mucine (tim-1) et leurs utilisations
DK1620544T3 (en)	2003-04-17	2019-01-14	Alnylam Pharmaceuticals Inc	MODIFIED iRNA AGENTS
CA2530285C (fr)	2003-06-27	2019-12-24	Abgenix, Inc.	Anticorps diriges contre les mutants de deletion du recepteur du facteur de croissance epidermique et utilisations correspondantes
CN1838968A (zh)	2003-08-08	2006-09-27	艾伯吉尼斯公司	针对甲状旁腺激素(pth)之抗体和其用途
CN1274814C (zh) *	2003-09-23	2006-09-13	李宁	一种提高转基因动物生产效率的方法
WO2005092926A2 (fr)	2004-03-19	2005-10-06	Amgen Inc.	Reduction du risque d'anticorps humains et anti-humains par la manipulation du gene v
JP5112863B2 (ja)	2004-07-01	2013-01-09	ノヴォノルディスクアー／エス	ヒト抗−ｋｉｒ抗体
WO2006047603A2 (fr)	2004-10-22	2006-05-04	Revivicor, Inc.	Ongules dotes de systemes immunitaires a modification genetique
US20080026457A1 (en)	2004-10-22	2008-01-31	Kevin Wells	Ungulates with genetically modified immune systems
WO2006055638A2 (fr)	2004-11-17	2006-05-26	Abgenix, Inc.	Anticorps monoclonaux entierement humains diriges contre l'il-13
WO2006068975A2 (fr)	2004-12-20	2006-06-29	Abgenix, Inc.	Proteines de liaison specifiques de la matriptase humaine
MX2007007484A (es)	2004-12-21	2007-07-20	Astrazeneca Ab	Anticuerpos dirigidos a angiopoyetina 2 y usos de los mismos.
AU2006208286A1 (en)	2005-01-26	2006-08-03	Amgen Fremont Inc.	Antibodies against interleukin-1 beta
WO2007059082A1 (fr)	2005-11-10	2007-05-24	Curagen Corporation	Methode de traitement du cancer de l'ovaire et du rein utilisant des anticorps diriges contre l'antigene a domaine 1 de mucine et a domaine immunoglobuline des lymphocytes t (tim-1)
KR101372690B1 (ko)	2005-12-13	2014-03-17	아스트라제네카 아베	인슐린 유사 성장 인자에 특이적인 결합 단백질 및 이의용도
AR056857A1 (es)	2005-12-30	2007-10-24	U3 Pharma Ag	Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos
HUE028179T2 (en)	2006-01-12	2016-12-28	Alexion Pharma Inc	Antibodies to OX-2 / CD200 and their use
EP2010567A2 (fr)	2006-04-07	2009-01-07	The Government of the United States of America as Represented by The Department of Health and Human Services	Compositions d'anticorps et méthodes de traitement d'une maladie néoplasique
TW200813091A (en)	2006-04-10	2008-03-16	Amgen Fremont Inc	Targeted binding agents directed to uPAR and uses thereof
CL2007002225A1 (es)	2006-08-03	2008-04-18	Astrazeneca Ab	Agente de union especifico para un receptor del factor de crecimiento derivado de plaquetas (pdgfr-alfa); molecula de acido nucleico que lo codifica; vector y celula huesped que la comprenden; conjugado que comprende al agente; y uso del agente de un
CN101553505B (zh)	2006-08-03	2013-07-17	阿斯利康(瑞典)有限公司	针对αVβ6的抗体及其应用
PL2125894T3 (pl)	2007-03-22	2019-08-30	Biogen Ma Inc.	Białka wiążące, w tym przeciwciała, pochodne przeciwciał i fragmenty przeciwciał, które swoiście wiążą się z CD154 i ich zastosowania
CN101802211B (zh)	2007-08-02	2014-10-01	诺维莫尼公司	抗正常t细胞表达和分泌活化调节因子(rantes)抗体及其使用方法
JOP20080381B1 (ar)	2007-08-23	2023-03-28	Amgen Inc	بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
EP4248976A3 (fr)	2007-08-23	2024-04-10	Amgen Inc.	Protéines de liaison à un antigène pour proprotéine convertase subtilisine kexine de type 9 (pcsk9)
EP2207809B1 (fr)	2007-09-26	2013-07-03	U3 Pharma GmbH	Protéines de liaison avec l'antigène du facteur de croissance de type facteur de croissance épidermique se liant à l'héparine
KR20100097684A (ko)	2007-11-12	2010-09-03	우드라이 파마 게엠베하	Ａｘｌ 항체
CA3043911A1 (fr)	2007-12-04	2009-07-02	Arbutus Biopharma Corporation	Lipides de ciblage
US8575123B2 (en)	2008-04-11	2013-11-05	Tekmira Pharmaceuticals Corporation	Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
JP5778577B2 (ja)	2008-09-19	2015-09-16	メディミューン，エルエルシー	Ｄｌｌ４に対する抗体およびその使用
ES2548377T3 (es)	2008-10-27	2015-10-16	Revivicor, Inc.	Ungulados inmunodeprimidos
PL2894165T3 (pl)	2008-11-10	2023-04-17	Alexion Pharmaceuticals, Inc.	Sposoby i kompozycje do leczenia zaburzeń układu dopełniacza
WO2010072740A2 (fr)	2008-12-23	2010-07-01	Astrazeneca Ab	Agents de liaison ciblés dirigés contre α5β1 et leurs applications
BRPI1014544B8 (pt)	2009-05-05	2021-05-25	Novimmune Sa	anticorpo anti-il-17f monoclonal totalmente humano isolado e composição farmacêutica compreendendo o mesmo
US20130045192A1 (en)	2009-11-09	2013-02-21	Alexion Pharmaceuticals, Inc.	Reagents and methods for detecting pnh type ii white blood cells and their identification as risk factors for thrombotic disorders
PL3351558T3 (pl)	2009-11-13	2020-08-24	Daiichi Sankyo Europe Gmbh	Materiał i sposoby leczenia lub zapobiegania chorobom związanym z HER-3
PL3279215T3 (pl)	2009-11-24	2020-06-29	Medimmune Limited	Ukierunkowane środki wiążące przeciwko B7-H1
CN102906115A (zh)	2010-01-11	2013-01-30	阿雷克森制药公司	在经抗cd200抗体治疗的人体内的免疫调节效应的生物标记
WO2011109427A2 (fr)	2010-03-01	2011-09-09	Alnylam Pharmaceuticals, Inc.	Amélioration de l'activité biologique de parni par modulation de son profil thermodynamique
PT2563813E (pt)	2010-04-30	2015-11-26	Alexion Pharma Inc	Anticorpos anti-c5a e métodos para utilização dos anticorpos
MX2012014975A (es)	2010-06-22	2013-03-12	Univ Colorado Regents	Anticuerpos al fragmento c3d de componente 3 de complemento.
US20120156130A1 (en)	2010-08-06	2012-06-21	Thore Hettmann	Use of her3 binding agents in prostate treatment
EP2668207A4 (fr)	2011-01-24	2015-06-10	Univ Singapore	Protéines de liaison à l'antigène lipoarabinomannane coiffé d'un mannose provenant de mycobactéries pathogènes
TW201244737A (en)	2011-02-03	2012-11-16	Alexion Pharma Inc	Use of an anti-CD200 antibody for prolonging the survival of allografts
JP5908972B2 (ja)	2011-04-07	2016-04-26	アムジエン・インコーポレーテツド	新規な抗原結合タンパク質
WO2012142164A1 (fr)	2011-04-12	2012-10-18	The United States Of America, As Represented By The Secretary, Department Of Health & Human Services	Anticorps monoclonaux humains qui se lient aux facteurs de croissance insulinomimétique (igf) de type i et ii
JOP20200043A1 (ar)	2011-05-10	2017-06-16	Amgen Inc	طرق معالجة أو منع الاضطرابات المختصة بالكوليسترول
WO2012158818A2 (fr)	2011-05-16	2012-11-22	Fabion Pharmaceuticals, Inc.	Protéines de fusion contenant un fab multi-spécifique et procédé d'utilisation
SG10201800715PA (en)	2011-06-21	2018-02-27	Alnylam Pharmaceuticals Inc	Angiopoietin-like 3 (angptl3) irna compostions and methods of use thereof
US9156911B2 (en)	2011-07-18	2015-10-13	Amgen Inc.	Apelin antigen-binding proteins and uses thereof
EP2773373B1 (fr)	2011-11-01	2018-08-22	Bionomics, Inc.	Procédés de blocage de la croissance des cellules souches cancéreuses
WO2013067060A1 (fr)	2011-11-01	2013-05-10	Bionomics, Inc.	Anticorps anti-gpr49
CN104053671A (zh)	2011-11-01	2014-09-17	生态学有限公司	治疗癌症的抗体和方法
US9220774B2 (en)	2011-11-01	2015-12-29	Bionomics Inc.	Methods of treating cancer by administering anti-GPR49 antibodies
JP2015500205A (ja)	2011-11-16	2015-01-05	アムジエン・インコーポレーテツド	上皮成長因子欠失変異体ｖｉｉｉ関連障害の治療方法
WO2013075035A1 (fr)	2011-11-18	2013-05-23	Alnylam Pharmaceuticals	Agents arni, compositions et procédés d'utilisation de ceux-ci pour traiter des maladies associées à la transthyrétine (ttr)
MX359548B (es)	2011-11-18	2018-10-02	Alnylam Pharmaceuticals Inc	Agentes de iarn modificados.
SG11201404638SA (en)	2012-02-06	2014-09-26	Inhibrx Llc	Cd47 antibodies and methods of use thereof
US9127274B2 (en)	2012-04-26	2015-09-08	Alnylam Pharmaceuticals, Inc.	Serpinc1 iRNA compositions and methods of use thereof
EA039663B1 (ru)	2012-05-03	2022-02-24	Амген Инк.	Применение антитела против pcsk9 для снижения сывороточного холестерина лпнп и лечения связанных с холестерином расстройств
SG10201610356YA (en)	2012-06-11	2017-01-27	Amgen Inc	Dual receptor antagonistic antigen-binding proteins and uses thereof
AU2013296321B2 (en)	2012-08-03	2019-05-16	Alnylam Pharmaceuticals, Inc.	Modified RNAi agents
EP4083209A1 (fr)	2012-12-05	2022-11-02	Alnylam Pharmaceuticals, Inc.	Compositions d'arni pcsk9 et leurs procédés d'utilisation
JO3519B1 (ar)	2013-01-25	2020-07-05	Amgen Inc	تركيبات أجسام مضادة لأجل cdh19 و cd3
US9920121B2 (en)	2013-01-25	2018-03-20	Amgen Inc.	Antibodies targeting CDH19 for melanoma
EP2953643B1 (fr)	2013-02-06	2023-02-22	Inhibrx, Inc.	Anticorps cd47 n'induisant ni l'appauvrissement en globules rouges ni l'appauvrissement en plaquettes et methodes d'utilisation de ceux-ci
SG10201912286TA (en)	2013-03-14	2020-02-27	Alnylam Pharmaceuticals Inc	COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2014140368A1 (fr)	2013-03-15	2014-09-18	Amgen Research (Munich) Gmbh	Constructions d'anticorps pour m2 et cd3 de grippe
LT2970449T (lt)	2013-03-15	2019-11-25	Amgen Res Munich Gmbh	Viengrandės surišančios molekulės, apimančios n galo abp
RU2015154738A (ru)	2013-05-22	2017-06-27	Элнилэм Фармасьютикалз, Инк.	КОМПОЗИЦИИ НА ОСНОВЕ iRNA TMPRSS6 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
HUE038146T2 (hu)	2013-05-22	2018-09-28	Alnylam Pharmaceuticals Inc	Serpina1 IRNS készítmények és eljárások alkalmazásukra
JP6267792B2 (ja)	2013-06-28	2018-01-24	アムジエン・インコーポレーテツド	ホモ接合性家族性高コレステロール血症の治療方法
US10077304B2 (en)	2013-08-14	2018-09-18	The Governing Council Of The University Of Toronto	Antibodies against frizzled receptor
TW201610151A (zh)	2013-09-23	2016-03-16	阿尼拉製藥公司	治療或預防與甲狀腺素運載蛋白相關疾病之方法
CA3107872A1 (fr)	2013-12-12	2015-06-18	Alnylam Pharmaceuticals, Inc.	Composition d'arni d'element de complement et procedes pour les utiliser
US10119136B2 (en)	2014-01-09	2018-11-06	Alnylam Pharmaceuticals, Inc.	RNAi agents modified at the 4′-C position
EA201691587A1 (ru)	2014-02-11	2017-01-30	Элнилэм Фармасьютикалз, Инк.	КОМПОЗИЦИИ НА ОСНОВЕ iRNA ДЛЯ КЕТОГЕКСОКИНАЗЫ (KHK) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
EP3126397B1 (fr)	2014-04-04	2020-01-29	Bionomics, Inc.	Anticorps humanisés qui se lient à lgr5
CA3215908A1 (fr)	2014-05-22	2015-11-26	Alnylam Pharmaceuticals, Inc.	Compositions d'arni produisant un effet sur l'angiotensinogene (agt) et leurs procedes d'utilisation
TWI695011B (zh)	2014-06-18	2020-06-01	美商梅爾莎納醫療公司	抗ｈｅｒ２表位之單株抗體及其使用之方法
TW201609812A (zh)	2014-07-31	2016-03-16	安美基研究（慕尼黑）公司	最佳化之跨物種特異性雙特異性單鏈抗體構築體
UY36245A (es)	2014-07-31	2016-01-29	Amgen Res Munich Gmbh	Constructos de anticuerpos para cdh19 y cd3
CA2952540C (fr)	2014-07-31	2022-06-21	Amgen Research (Munich) Gmbh	Construction d'anticorps monocatenaires bispecifiques avec distribution tissulaire amelioree
KR20240010762A (ko)	2014-08-20	2024-01-24	알닐람 파마슈티칼스 인코포레이티드	변형 이중-가닥 rna 제제
EP3191591A1 (fr)	2014-09-12	2017-07-19	Alnylam Pharmaceuticals, Inc.	Agents polynucléotidiques ciblant le composant du complément c5 et leurs méthodes d'utilisation
US20170304459A1 (en)	2014-10-10	2017-10-26	Alnylam Pharmaceuticals, Inc.	Methods and compositions for inhalation delivery of conjugated oligonucleotide
JOP20200115A1 (ar)	2014-10-10	2017-06-16	Alnylam Pharmaceuticals Inc	تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
WO2016061487A1 (fr)	2014-10-17	2016-04-21	Alnylam Pharmaceuticals, Inc.	Agents polynucléotidiques de ciblage d'acide aminolévulinique synthase-1 (alas1) et utilisations de ceux-ci
WO2016069694A2 (fr)	2014-10-30	2016-05-06	Alnylam Pharmaceuticals, Inc.	Agents polynucléotidiques ciblant serpinc 1 (at3) et leurs méthodes d'utilisation
JOP20200092A1 (ar)	2014-11-10	2017-06-16	Alnylam Pharmaceuticals Inc	تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
JP2017535552A (ja)	2014-11-17	2017-11-30	アルナイラムファーマシューティカルズ，インコーポレイテッドＡｌｎｙｌａｍＰｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ．	アポリポタンパク質Ｃ３（ＡＰＯＣ３）ｉＲＮＡ組成物およびその使用方法
WO2016130806A2 (fr)	2015-02-13	2016-08-18	Alnylam Pharmaceuticals, Inc.	Compositions d'arni du gène codant pour la protéine 3 contenant un domaine phospholipase de type patatine (pnpla3) et leurs procédés d'utilisation
MX2017012610A (es)	2015-04-08	2018-03-16	Alnylam Pharmaceuticals Inc	Composiciones y metodos para inhibir la expresion del gen lect2.
SI3283524T1 (sl)	2015-04-17	2023-06-30	Amgen Research (Munich) Gmbh	Bispecifični konstrukti protiteles za CDH3 in CD3
KR20180002688A (ko)	2015-05-06	2018-01-08	알닐람 파마슈티칼스 인코포레이티드	인자 ＸＩＩ(하게만 인자)(Ｆ12), 칼리크레인 Ｂ, 혈장(플레처 인자) 1(ＫＬＫＢ1) 및 키니노겐 1(ＫＮＧ1) ｉＲＮＡ 조성물 및 그의 이용 방법
EP3307316A1 (fr)	2015-06-12	2018-04-18	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de composant du complément c5 et leurs procédés d'utilisation
WO2016205323A1 (fr)	2015-06-18	2016-12-22	Alnylam Pharmaceuticals, Inc.	Agents polynucléotidiques ciblant l'hydroxyacide oxydase (glycolate oxydase, hao1) et procédés d'utilisation de ceux-ci
WO2016209862A1 (fr)	2015-06-23	2016-12-29	Alnylam Pharmaceuticals, Inc.	Compositions d'arndb contre un gène de glucokinase (gck) et leurs procédés d'utilisation
WO2017011286A1 (fr)	2015-07-10	2017-01-19	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de la sous-unité acide labile de la protéine se liant au facteur de croissance apparenté a l'insuline (igfals) et du facteur de croissance 1 apparenté a l'insuline (igf-1) et leurs procédés d'utilisation
TWI793062B (zh)	2015-07-31	2023-02-21	德商安美基研究（慕尼黑）公司	Ｄｌｌ３及ｃｄ３抗體構築體
TWI796283B (zh)	2015-07-31	2023-03-21	德商安美基研究（慕尼黑）公司	Ｍｓｌｎ及ｃｄ３抗體構築體
TWI829617B (zh)	2015-07-31	2024-01-21	德商安美基研究（慕尼黑）公司	Ｆｌｔ３及ｃｄ３抗體構築體
TWI717375B (zh)	2015-07-31	2021-02-01	德商安美基研究（慕尼黑）公司	Ｃｄ７０及ｃｄ３抗體構築體
TWI744242B (zh)	2015-07-31	2021-11-01	德商安美基研究（慕尼黑）公司	Egfrviii及cd3抗體構築體
EP3344769B1 (fr)	2015-09-02	2024-04-17	Alnylam Pharmaceuticals, Inc.	Compositions d'arni contre le programmed cell death 1 ligand 1 (pd-l1) et procédés pour leur utilisations
EP3350328A1 (fr)	2015-09-14	2018-07-25	Alnylam Pharmaceuticals, Inc.	Agents de polynucléotide ciblant un domaine de phospholipase de type patatine contenant 3 (pnpla3) et leurs procédés d'utilisation
EP3387129A1 (fr)	2015-12-10	2018-10-17	Alnylam Pharmaceuticals, Inc.	COMPOSITIONS D'ARNi CHAPERON (SCAP) DE LA PROTÉINE SREBP (STEROL REGULATORY ELEMENT BINDING PROTEIN), ET PROCÉDÉS D'UTILISATION ASSOCIÉS
EA039859B1 (ru)	2016-02-03	2022-03-21	Эмджен Рисерч (Мюник) Гмбх	Биспецифические конструкты антител, связывающие egfrviii и cd3
CN114716557A (zh)	2016-02-03	2022-07-08	安进研发（慕尼黑）股份有限公司	Psma和cd3双特异性t细胞接合抗体构建体
HUE057220T2 (hu)	2016-02-03	2022-04-28	Amgen Res Munich Gmbh	BCMA és CD3 bispecifikus, T-sejtet kötõ antitest-konstrukciók
CN109476756B (zh)	2016-03-15	2022-05-31	埃泰美德(香港)有限公司	一种多特异性Fab融合蛋白及其用途
CA3016474A1 (fr)	2016-03-15	2017-09-21	Mersana Therapeutics, Inc.	Conjugues anticorps-medicament ciblant napi2b et leurs procedes d'utilisation
CN108697799A (zh)	2016-03-22	2018-10-23	生态学有限公司	抗lgr5单克隆抗体的施用
JOP20170091B1 (ar)	2016-04-19	2021-08-17	Amgen Res Munich Gmbh	إعطاء تركيبة ثنائية النوعية ترتبط بـ cd33 وcd3 للاستخدام في طريقة لعلاج اللوكيميا النخاعية
US20190256845A1 (en)	2016-06-10	2019-08-22	Alnylam Pharmaceuticals, Inc.	COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
TW201825674A (zh)	2016-09-09	2018-07-16	美商艾斯合顧問有限公司	表現雙特異性接合分子的溶瘤病毒
TW202313978A (zh)	2016-11-23	2023-04-01	美商阿尼拉製藥公司	絲胺酸蛋白酶抑制因子Ａ１ｉＲＮＡ組成物及其使用方法
WO2018112320A1 (fr)	2016-12-16	2018-06-21	Alnylam Pharmaceuticals, Inc.	Méthodes de traitement ou de prévention de maladies associées à ttr à l'aide de compositions d'arni de transthyrétine (ttr)
JOP20190189A1 (ar)	2017-02-02	2019-08-01	Amgen Res Munich Gmbh	تركيبة صيدلانية ذات درجة حموضة منخفضة تتضمن بنيات جسم مضاد يستهدف الخلية t
CA3059446A1 (fr)	2017-04-18	2018-10-25	Alnylam Pharmaceuticals, Inc.	Methodes pour le traitement de sujets atteints d'une infection par le virus de l'hepatite b (vhb)
MX2019013142A (es)	2017-05-05	2019-12-16	Amgen Inc	Composicion farmaceutica que comprende construcciones de anticuerpos biespecificas para mejorar el almacenamiento y la administracion.
CA3078971A1 (fr)	2017-11-01	2019-05-09	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de composant du complement c3 et leurs procedes d'utilisation
EP3714054A1 (fr)	2017-11-20	2020-09-30	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de composant p amyloïde serique et leurs procédés d'utilisation
SG11202004273YA (en)	2017-12-11	2020-06-29	Amgen Inc	Continuous manufacturing process for bispecific antibody products
WO2019126651A1 (fr)	2017-12-21	2019-06-27	Alnylam Pharmaceuticals, Inc.	Agents d'arn double brin à enrichissement chiral
UY38041A (es)	2017-12-29	2019-06-28	Amgen Inc	Construcción de anticuerpo biespecífico dirigida a muc17 y cd3
MA53325A (fr)	2018-07-30	2021-06-09	Amgen Inc	Administration prolongée d'une construction d'anticorps bispécifique se liant à cd33 et cd3
SG11202100987RA (en)	2018-08-03	2021-02-25	Amgen Res Munich Gmbh	Antibody constructs for cldn18.2 and cd3
FI3843757T3 (fi)	2018-08-27	2024-06-06	Affimed Gmbh	Kryosäilötyt nk-solut, jotka on esiladattu vasta-ainerakenteella
EP3853364A1 (fr)	2018-09-18	2021-07-28	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de cétohexokinase (khk) et leurs procédés d'utilisation
SG11202103275YA (en)	2018-10-11	2021-04-29	Amgen Inc	Downstream processing of bispecific antibody constructs
US10913951B2 (en)	2018-10-31	2021-02-09	University of Pittsburgh—of the Commonwealth System of Higher Education	Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure
US20220056444A1 (en)	2018-12-05	2022-02-24	Empirico Inc.	Process to inhibit or eliminate eosinophilic diseases of the airway and related conditions
CA3123617A1 (fr)	2018-12-20	2020-06-25	Praxis Precision Medicines, Inc.	Compositions et methodes pour le traitement des maladies associes a kcnt1
EP3911632A1 (fr)	2019-01-15	2021-11-24	Empirico Inc.	Promédicaments d'inhibiteurs de l'alox-15 et leurs procédés d'utilisation
AU2020279101A1 (en)	2019-05-17	2021-11-18	Alnylam Pharmaceuticals, Inc.	Oral delivery of oligonucleotides
TW202045711A (zh)	2019-06-13	2020-12-16	美商安進公司	生物製品製造中基於生物量之自動灌注控制
EP4004041A1 (fr)	2019-07-26	2022-06-01	Amgen Inc.	Protéines de liaison à un antigène anti-il13
WO2021030522A1 (fr)	2019-08-13	2021-02-18	Alnylam Pharmaceuticals, Inc.	Compositions d'agent d'arni à sous-unité de protéine ribosomale 25 (rps25) et leurs procédés d'utilisation
CA3152946A1 (fr)	2019-09-10	2021-03-18	Amgen Inc.	Procede de purification de polypeptides de liaison a un antigene bispecifique presentant une capacite de liaison dynamique de capture de proteine l amelioree
CN114728018B (zh)	2019-11-01	2024-07-19	阿尔尼拉姆医药品有限公司	亨廷顿(HTT)iRNA药剂组合物及其使用方法
CA3156683A1 (fr)	2019-11-13	2021-05-20	Amgen Inc.	Procede de reduction de la formation d'agregats dans le traitement en aval de molecules de liaison a l'antigene bispecifiques
EP4061945A1 (fr)	2019-11-22	2022-09-28	Alnylam Pharmaceuticals, Inc.	Compositions d'agent arni d'ataxine 3 (atxn3) et leurs procédés d'utilisation
JP2023506181A (ja)	2019-12-13	2023-02-15	アルナイラムファーマシューティカルズ，インコーポレイテッド	ヒト第９染色体オープンリーディングフレーム７２（Ｃ９ＯＲＦ７２）ｉＲＮＡ剤組成物およびその使用方法
UY38995A (es)	2019-12-20	2021-06-30	Amgen Inc	Constructos de anticuerpo multiespecíficos agonistas de cd40 dirigidos a mesotelina para el tratamiento de tumores sólidos
JP2023508366A (ja)	2019-12-27	2023-03-02	アフィメッドゲゼルシャフトミットベシュレンクテルハフツンク	二重特異性ｆｃｙｒｉｉｉ×ｃｄ３０抗体構築体の製造方法
US20230093169A1 (en)	2020-01-22	2023-03-23	Amgen Research (Munch) Gmbh	Combinations of antibody constructs and inhibitors of cytokine release syndrome and uses thereof
WO2021154941A1 (fr)	2020-01-31	2021-08-05	Alnylam Pharmaceuticals, Inc.	Compositions d'arni du composant c5 du complément destinées à être utilisées dans le traitement de la sclérose latérale amyotrophique (sla)
WO2021178607A1 (fr)	2020-03-05	2021-09-10	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de composant c3 du complément et leurs procédés d'utilisation pour le traitement ou la prévention de maladies associées au composant c3 du complément
WO2021183861A1 (fr)	2020-03-12	2021-09-16	Amgen Inc.	Méthodes de traitement et de prophylaxie du crs chez des patients, comprenant une association d'anticorps bispécifiques se liant à une cellule tumorale du cds x et d'un inhibiteur du tnf alpha ou de l'il-6
CA3175275A1 (fr)	2020-03-19	2021-09-23	Amgen Inc.	Anticorps contre la mucine 17 et leurs utilisations
EP4127168A1 (fr)	2020-03-26	2023-02-08	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de coronavirus et leurs procédés d'utilisation
WO2021206917A1 (fr)	2020-04-07	2021-10-14	Alnylam Pharmaceuticals, Inc.	Compositions arni d'enzyme de conversion de l'angiotensine 2 (eca2) et procédés d'utilisation associés
EP4133077A1 (fr)	2020-04-07	2023-02-15	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de la serine protease 2 transmembranaire (tmprss2) et leurs procédés d'utilisation
CA3181400A1 (fr)	2020-04-27	2021-11-04	Alnylam Pharmaceuticals, Inc.	Compositions d'agent d'arni de l'apolipoproteine e (apoe) et leurs procedes d'utilisation
WO2021231691A1 (fr)	2020-05-15	2021-11-18	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar de rétinoschisine 1 (rs1)
WO2021231679A1 (fr)	2020-05-15	2021-11-18	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar de la protéine bêta 2 de jonction lacunaire (gjb2)
EP4150077A1 (fr)	2020-05-15	2023-03-22	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar de la protéine 1 de type canal transmembranaire (tmc1)
EP4150090A1 (fr)	2020-05-15	2023-03-22	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar d'otoferline (otof)
EP4150078A1 (fr)	2020-05-15	2023-03-22	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar d'argininosuccinate lyase (asl)
EP4150076A1 (fr)	2020-05-15	2023-03-22	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar de la protéine 2 de liaison méthyl-cpg (mecp2)
WO2021231673A1 (fr)	2020-05-15	2021-11-18	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar de la kinase 2 à répétition riche en leucine (lrrk2)
CA3162416C (fr)	2020-05-15	2023-07-04	Korro Bio, Inc.	Procedes et compositions pour l'edition mediee par adar d'argininosuccinate synthetase (ass1)
EP4153633A1 (fr)	2020-05-19	2023-03-29	Amgen Inc.	Constructions de liaison à mageb2
MX2022014902A (es)	2020-05-29	2023-01-04	Amgen Inc	Administracion mitigadora de efectos adversos de un constructo biespecifico que se une a cd33 y cd3.
US11408000B2 (en)	2020-06-03	2022-08-09	Triplet Therapeutics, Inc.	Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity
WO2021252557A1 (fr)	2020-06-09	2021-12-16	Alnylam Pharmaceuticals, Inc.	Compositions d'arni et leurs procédés d'utilisation pour une administration par inhalation
JP2023540429A (ja)	2020-07-10	2023-09-25	アンセルム（アンスティチュート・ナシオナル・ドゥ・ラ・サンテ・エ・ドゥ・ラ・ルシェルシュ・メディカル）	てんかんを治療するための方法及び組成物
EP4217489A1 (fr)	2020-09-24	2023-08-02	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de dipeptidyle peptidase 4 (dpp4) et leurs procédés d'utilisation
TW202229552A (zh)	2020-10-05	2022-08-01	美商艾拉倫製藥股份有限公司	Ｇ蛋白－偶合受體７５（ＧＰＲ７５）ｉＲＮＡ組成物及其使用方法
AU2021357841A1 (en)	2020-10-08	2023-06-15	Affimed Gmbh	Trispecific binders
AU2021365822A1 (en)	2020-10-21	2023-06-08	Alnylam Pharmaceuticals, Inc.	Methods and compositions for treating primary hyperoxaluria
WO2022087329A1 (fr)	2020-10-23	2022-04-28	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de la mucine 5b (muc5b) et leurs méthodes d'utilisation
UY39507A (es)	2020-11-06	2022-03-31	Amgen Res Munich Gmbh	Construcciones polipeptídicas que se unen selectivamente a cldn6 y cd3
BR112023008670A2 (pt)	2020-11-06	2024-02-06	Amgen Inc	Construtos polipeptídicos ligados à cd3
CN116323671A (zh)	2020-11-06	2023-06-23	安进公司	具有增加的选择性的多靶向性双特异性抗原结合分子
CA3198064A1 (fr)	2020-11-06	2022-05-12	Amgen Inc.	Domaine de liaison a l'antigene a taux de coupure reduit
CA3201452A1 (fr)	2020-12-01	2022-06-09	Alnylam Pharmaceuticals, Inc.	Methodes et compositions pour l'inhibition de l'expression du gene de l'hao1 (hydroxyacide oxydase 1 (glycolate oxydase))
KR20230146048A (ko)	2021-02-12	2023-10-18	알닐람 파마슈티칼스 인코포레이티드	슈퍼옥사이드 디스뮤타제 1(sod1) irna 조성물 및 슈퍼옥사이드 디스뮤타제 1- (sod1-) 관련 신경퇴행성 질환을 치료하거나 예방하기 위한 이의 사용 방법
WO2022182864A1 (fr)	2021-02-25	2022-09-01	Alnylam Pharmaceuticals, Inc.	Compositions à base d'arni de protéine prion (prnp) et procédés et procédés d'utilisation de celles-ci
WO2022192519A1 (fr)	2021-03-12	2022-09-15	Alnylam Pharmaceuticals, Inc.	Compositions d'arni de la glycogène synthase kinase 3 alpha (gsk3a) et leurs procédés d'utilisation
AR125230A1 (es)	2021-03-29	2023-06-28	Alnylam Pharmaceuticals Inc	COMPOSICIONES DE AGENTES DE ARNi CONTRA HUNTINGTINA (HTT) Y SUS MÉTODOS DE USO
CA3215594A1 (fr)	2021-04-02	2022-10-06	Agnieszka KIELCZEWSKA	Constructions de liaison a mageb2
JP2024519293A (ja)	2021-04-29	2024-05-10	アルナイラムファーマシューティカルズ，インコーポレイテッド	シグナル伝達兼転写活性化因子６（ＳＴＡＴ６）ｉＲＮＡ組成物およびその使用方法
CN117279947A (zh)	2021-05-06	2023-12-22	安进研发（慕尼黑）股份有限公司	用于在增殖性疾病中使用的靶向cd20和cd22的抗原结合分子
JP2024522068A (ja)	2021-05-18	2024-06-11	アルナイラムファーマシューティカルズ，インコーポレイテッド	ナトリウム－グルコース共輸送体２（ｓｇｌｔ２）ｉｒｎａ組成物およびその使用方法
EP4341405A1 (fr)	2021-05-20	2024-03-27	Korro Bio, Inc.	Procédés et compositions pour l'édition médiée par adar
WO2022256283A2 (fr)	2021-06-01	2022-12-08	Korro Bio, Inc.	Méthodes de restauration de la fonction protéique par adar
AR126000A1 (es)	2021-06-04	2023-08-30	Alnylam Pharmaceuticals Inc	Agentes de arni del marco de lectura abierto 72 del cromosoma 9 humano (c9orf72), composiciones y métodos de uso de los mismos
WO2023278410A1 (fr)	2021-06-29	2023-01-05	Korro Bio, Inc.	Procédés et compositions pour édition médiée par adar
US20230194709A9 (en)	2021-06-29	2023-06-22	Seagate Technology Llc	Range information detection using coherent pulse sets with selected waveform characteristics
JP2024528701A (ja)	2021-07-23	2024-07-30	アルナイラムファーマシューティカルズ，インコーポレイテッド	ベータカテニン（ＣＴＮＮＢ１）ｉＲＮＡ組成物およびその使用方法
EP4376958A1 (fr)	2021-07-30	2024-06-05	Affimed GmbH	Corps duplex
EP4419683A1 (fr)	2021-10-22	2024-08-28	Korro Bio, Inc.	Procédés et compositions pour perturber l'interaction de la protéine nrf2-keap1 par l'édition d'arn à médiation adar
EP4423272A2 (fr)	2021-10-29	2024-09-04	Alnylam Pharmaceuticals, Inc.	Compositions d'agent d'arni de la huntingtine (htt) et leurs procédés d'utilisation
WO2023078968A1 (fr)	2021-11-03	2023-05-11	Affimed Gmbh	Liants de cd16a bispécifiques
CA3237018A1 (fr)	2021-11-03	2023-05-11	Joachim Koch	Liants de cd16a bispecifiques
KR20240126870A (ko)	2021-12-22	2024-08-21	캠프4 테라퓨틱스 코포레이션	조절 rna들을 표적으로 하는 안티센스 올리고뉴클레오티드를 사용한 유전자 전사의 조절
WO2023141314A2 (fr)	2022-01-24	2023-07-27	Alnylam Pharmaceuticals, Inc.	Compositions d'agent d'arni d'enzyme de voie de biosynthèse de sulfate d'héparine et leurs méthodes d'utilisation
WO2023218027A1 (fr)	2022-05-12	2023-11-16	Amgen Research (Munich) Gmbh	Molécules bispécifiques multicibles à chaînes multiples de liaison à un antigène à sélectivité accrue
WO2023240277A2 (fr)	2022-06-10	2023-12-14	Camp4 Therapeutics Corporation	Méthodes de modulation de l'expression de progranuline à l'aide d'oligonucléotides antisens ciblant des arn régulateurs
WO2024059675A2 (fr)	2022-09-14	2024-03-21	Amgen Inc.	Composition de stabilisation de molécule bispécifique
TW202424193A (zh)	2022-09-15	2024-06-16	美商艾拉倫製藥股份有限公司	第１３型１７β－羥基類固醇去氫酶（ＨＳＤ１７Ｂ１３）ｉＲＮＡ組成物及其使用方法
WO2024119145A1 (fr)	2022-12-01	2024-06-06	Camp4 Therapeutics Corporation	Modulation de la transcription du gène syngap1 à l'aide d'oligonucléotides antisens ciblant les arn régulateurs

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4873191A (en) *	1981-06-12	1989-10-10	Ohio University	Genetic transformation of zygotes
US4736866A (en) *	1984-06-22	1988-04-12	President And Fellows Of Harvard College	Transgenic non-human mammals
US5175385A (en) *	1987-09-03	1992-12-29	Ohio University/Edison Animal Biotechnolgy Center	Virus-resistant transgenic mice
US5175384A (en) *	1988-12-05	1992-12-29	Genpharm International	Transgenic mice depleted in mature t-cells and methods for making transgenic mice

1993
- 1993-06-18 CA CA 2135313 patent/CA2135313A1/fr not_active Abandoned
- 1993-06-18 WO PCT/US1993/005873 patent/WO1994000569A1/fr not_active Application Discontinuation
- 1993-06-18 AU AU45410/93A patent/AU4541093A/en not_active Abandoned
- 1993-06-18 JP JP6502483A patent/JPH07508410A/ja not_active Ceased
- 1993-06-18 NZ NZ25394393A patent/NZ253943A/en unknown
- 1993-06-18 EP EP93915422A patent/EP0648265A4/fr not_active Withdrawn

Also Published As

Publication number	Publication date
EP0648265A4 (fr)	1996-12-04
NZ253943A (en)	1997-01-29
EP0648265A1 (fr)	1995-04-19
WO1994000569A1 (fr)	1994-01-06
JPH07508410A (ja)	1995-09-21
AU4541093A (en)	1994-01-24

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WO1996034097A1 (fr)	1996-10-31	MAMMIFERES NON HUMAINS CIBLES PAR GENE PRESENTANT UN DEFICIT EN GENE SOD-1, EXPRIMANT UNE SEQUENCE Aβ HUMANISEE A MUTATION SUEDOISE DE FAD
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