MX2021014534A - Modificación por ingeniería genética de la región bisagra para impulsar la dimerización de anticuerpos. - Google Patents

Modificación por ingeniería genética de la región bisagra para impulsar la dimerización de anticuerpos.

Info

Publication number
MX2021014534A
MX2021014534A MX2021014534A MX2021014534A MX2021014534A MX 2021014534 A MX2021014534 A MX 2021014534A MX 2021014534 A MX2021014534 A MX 2021014534A MX 2021014534 A MX2021014534 A MX 2021014534A MX 2021014534 A MX2021014534 A MX 2021014534A
Authority
MX
Mexico
Prior art keywords
engineering
hinge region
drive
mutations
dimer
Prior art date
Application number
MX2021014534A
Other languages
English (en)
Inventor
Zhulun Wang
Fernando Garces
Original Assignee
Amgen Inc
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.)
Filing date
Publication date
Application filed by Amgen Inc filed Critical Amgen Inc
Publication of MX2021014534A publication Critical patent/MX2021014534A/es

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • 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
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • C07K2317/526—CH3 domain
    • 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
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • 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
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

El potencial clínico de los anticuerpos multiespecíficos como anticuerpos biespecíficos y triespecíficos es muy prometedor para dirigirse a enfermedades complejas. Sin embargo, la generación de esas moléculas presenta grandes retos ya que, en muchos casos, se desea impulsar específicamente el apareamiento específico de múltiples cadenas polipeptídicas que están presentes en disoluciones. En el caso de las cadenas pesadas, hay dos regiones principales que forman una superficie de contacto de dímeros. Una de ellas es la región CH3, que se ha aprovechado ampliamente insertando o bien mutaciones de par de carga (CPM) para conducir la superficie de contacto de dímeros o bien insertando residuos voluminosos en cavidades (botón en ojal) para favorecer y desfavorecer físicamente la formación de dímeros. Sin embargo, cada una de estas estrategias puede no aplicarse a cada molécula y, por tanto, son necesarias más herramientas. En el presente documento, se describe la modificación por ingeniería genética de la región bisagra con un pequeño número de mutaciones que son capaces de impulsar por sí solas satisfactoriamente la dimerización de cadenas pesadas.
MX2021014534A 2019-05-30 2020-05-29 Modificación por ingeniería genética de la región bisagra para impulsar la dimerización de anticuerpos. MX2021014534A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962854907P 2019-05-30 2019-05-30
PCT/US2020/035196 WO2020243477A2 (en) 2019-05-30 2020-05-29 Engineering the hinge region to drive antibody dimerization

Publications (1)

Publication Number Publication Date
MX2021014534A true MX2021014534A (es) 2022-02-11

Family

ID=72234906

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2021014534A MX2021014534A (es) 2019-05-30 2020-05-29 Modificación por ingeniería genética de la región bisagra para impulsar la dimerización de anticuerpos.

Country Status (12)

Country Link
US (1) US20220235148A1 (es)
EP (1) EP3976643A2 (es)
JP (1) JP2022534901A (es)
KR (1) KR20220016139A (es)
CN (1) CN114174344A (es)
AU (1) AU2020283890A1 (es)
CA (1) CA3141690A1 (es)
EA (1) EA202193322A1 (es)
MX (1) MX2021014534A (es)
SG (1) SG11202112926YA (es)
TW (1) TW202110877A (es)
WO (1) WO2020243477A2 (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024017371A1 (zh) * 2022-07-22 2024-01-25 信达生物制药(苏州)有限公司 促进多特异性抗体的重链和轻链同源配对的突变体

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US30985A (en) 1860-12-18 Thomas l
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
US4965195A (en) 1987-10-26 1990-10-23 Immunex Corp. Interleukin-7
US4968607A (en) 1987-11-25 1990-11-06 Immunex Corporation Interleukin-1 receptors
AU632065B2 (en) 1988-09-23 1992-12-17 Novartis Vaccines And Diagnostics, Inc. Cell culture medium for enhanced cell growth, culture longevity and product expression
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
AU643427B2 (en) 1988-10-31 1993-11-18 Immunex Corporation Interleukin-4 receptors
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
SG48759A1 (en) 1990-01-12 2002-07-23 Abgenix Inc Generation of xenogenic antibodies
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
AU651596B2 (en) 1990-06-05 1994-07-28 Immunex Corporation Type II interleukin-1 receptors
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
ES2108048T3 (es) 1990-08-29 1997-12-16 Genpharm Int Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos.
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
JPH06508035A (ja) 1991-06-14 1994-09-14 ディーエヌエックス　コーポレーション トランスジェニックブタにおけるヒトヘモグロビンの生産
DE69224906T2 (de) 1991-07-08 1998-10-29 Univ Massachusetts Thermotropes flüssig-kristallines segment-blockcopolymer
EP0617706B1 (en) 1991-11-25 2001-10-17 Enzon, Inc. Multivalent antigen-binding proteins
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
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US6130364A (en) 1995-03-29 2000-10-10 Abgenix, Inc. Production of antibodies using Cre-mediated site-specific recombination
US6096871A (en) 1995-04-14 2000-08-01 Genentech, Inc. Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life
CA2219361C (en) 1995-04-27 2012-02-28 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP0904107B1 (en) 1996-03-18 2004-10-20 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
EP2305027B1 (en) 1996-12-03 2014-07-02 Amgen Fremont Inc. Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
US6660843B1 (en) 1998-10-23 2003-12-09 Amgen Inc. Modified peptides as therapeutic agents
US20030133939A1 (en) 2001-01-17 2003-07-17 Genecraft, Inc. Binding domain-immunoglobulin fusion proteins
US7829084B2 (en) 2001-01-17 2010-11-09 Trubion Pharmaceuticals, Inc. Binding constructs and methods for use thereof
EP1433793A4 (en) 2001-09-13 2006-01-25 Inst Antibodies Co Ltd METHOD FOR CREATING A CAMEL ANTIBODY LIBRARY
CA2577082A1 (en) 2004-09-02 2006-03-16 Genentech, Inc. Heteromultimeric molecules
SG170750A1 (en) 2006-03-17 2011-05-30 Biogen Idec Inc Stabilized polypeptide compositions
AU2008226067B2 (en) 2007-03-12 2012-11-08 Esbatech, An Alcon Biomedical Research Unit Llc Sequence based engineering and optimization of single chain antibodies
MX2009010282A (es) 2007-03-29 2009-10-12 Genmab As Anticuerpos biespecificos y metodos para su produccion.
US8793074B2 (en) 2007-06-21 2014-07-29 Saint Louis University Sequence covariance networks, methods and uses therefor
CN105017427A (zh) 2007-06-25 2015-11-04 艾斯巴技术-诺华有限责任公司 修饰抗体的方法和具有改善的功能性质的修饰抗体
CN103097417B (zh) 2010-04-20 2019-04-09 根马布股份公司 含异二聚体抗体fc的蛋白及其制备方法
EP2569337A1 (en) * 2010-05-14 2013-03-20 Rinat Neuroscience Corp. Heterodimeric proteins and methods for producing and purifying them
CA3051311A1 (en) 2010-05-27 2011-12-01 Genmab A/S Monoclonal antibodies against her2
KR102049803B1 (ko) 2011-10-27 2019-11-29 젠맵 에이/에스 이종이량체 단백질의 생산
CA2913370C (en) * 2013-05-31 2022-12-13 Zymeworks Inc. Heteromultimers with reduced or silenced effector function

Also Published As

Publication number Publication date
EA202193322A1 (ru) 2022-03-10
JP2022534901A (ja) 2022-08-04
US20220235148A1 (en) 2022-07-28
EP3976643A2 (en) 2022-04-06
TW202110877A (zh) 2021-03-16
CN114174344A (zh) 2022-03-11
SG11202112926YA (en) 2021-12-30
KR20220016139A (ko) 2022-02-08
AU2020283890A1 (en) 2021-12-16
WO2020243477A2 (en) 2020-12-03
CA3141690A1 (en) 2020-12-03
WO2020243477A3 (en) 2021-01-07

Similar Documents

Publication Publication Date Title
WO2020010250A3 (en) Anti-tcr antibody molecules and uses thereof
PE20200717A1 (es) Moleculas de anticuerpo que se unen a cd73 y usos de las mismas
SG11201900373WA (en) Bispecific proteins and methods for preparing same
AR106199A1 (es) Moléculas de unión a antígeno biespecíficas activadoras de células t
WO2018013818A3 (en) Antibodies against tim3 and uses thereof
WO2018085555A8 (en) Activatable anti-ctla-4 antibodies and uses thereof
WO2020236839A3 (en) Generation of protein sequences using machine learning techniques
CA2832534C (en) Method for the generation of compact tale-nucleases and uses thereof
EA201491569A1 (ru) МОДИФИЦИРОВАННЫЕ БИСПЕЦИФИЧЕСКИЕ АНТИТЕЛА IgG4 С СИММЕТРИЧНОЙ ПОСЛЕДОВАТЕЛЬНОСТЬЮ
MX2021014534A (es) Modificación por ingeniería genética de la región bisagra para impulsar la dimerización de anticuerpos.
WO2015138600A3 (en) Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies
MX2017008541A (es) Anticuerpos biespecificos contra calicreina y factor xii del plasma.
WO2012135740A3 (en) Cd37-binding molecules and immunoconjugates thereof
GB201005064D0 (en) Biological products
WO2020123425A3 (en) Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
CO2021008995A2 (es) Proteínas de unión multiespecíficas con dominios fab mutantes
EA201990894A1 (ru) Анти-pd-1/анти-her2 гетеродимерное биспецифическое антитело со структурой природного антитела и способ его получения
WO2019147863A3 (en) Mica/b antibodies and methods of use
WO2021138474A3 (en) Anti-tcr antibody molecules and uses thereof
CL2019002802A1 (es) Anticuerpos biespecíficos anti-pd-l1-anti-tim-3.
PH12019501588A1 (en) Pillow
PH12017500703A1 (en) Vehicle floor structure
CL2019002735A1 (es) Anticuerpos que se unen a steap-1.
WO2015073743A3 (en) Methods using monovalent antigen binding constructs targeting her2
PH12021550232A1 (en) Anti-mica/b antibodies that block mica/b shedding and methods of use