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AR093584A1 - Inmunoglobulinas heterodimericas - Google Patents

Inmunoglobulinas heterodimericas

Info

Publication number
AR093584A1
AR093584A1 ARP130104306A ARP130104306A AR093584A1 AR 093584 A1 AR093584 A1 AR 093584A1 AR P130104306 A ARP130104306 A AR P130104306A AR P130104306 A ARP130104306 A AR P130104306A AR 093584 A1 AR093584 A1 AR 093584A1
Authority
AR
Argentina
Prior art keywords
domain
amino acid
charged amino
antibody
fragment
Prior art date
Application number
ARP130104306A
Other languages
English (en)
Inventor
Florio Monica
Kannan Gunasekaran
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 AR093584A1 publication Critical patent/AR093584A1/es

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Classifications

    • 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
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • 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
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • 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
    • C07K2317/52—Constant or Fc region; Isotype
    • 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
    • C07K2317/56—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
    • C07K2317/50—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
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72—Increased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/75—Agonist effect on antigen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)

Abstract

Reivindicación 1: Un anticuerpo heterodimérico o su fragmento que comprende una o más sustituciones en cada uno de los siguientes dominios: un primer dominio CH₃, un segundo dominio CH₃, un dominio CH₁, un dominio CL, un dominio VH y un dominio VL, en donde una o más sustituciones introducen aminoácidos cargados que son electrostáticamente desfavorables para la formación de homodímeros y electrostáticamente favorables para la formación de heterodímeros. Reivindicación 25: Un anticuerpo heterodimérico o su fragmento que comprende una cadena pesada que comprende (a) una primera sustitución de aminoácido en una posición AHo seleccionada del grupo que consiste en las posiciones de AHo 42 - 50 que introduce un aminoácido cargado en dicha posición, (b) una segunda sustitución de aminoácido en una posición seleccionada del grupo que consiste en las posiciones 126 - 213 (numeración EU) que introduce un aminoácido cargado en dicha posición, (c) una tercera sustitución de aminoácido en una posición seleccionada del grupo que consiste en las posiciones 352 - 360 (numeración EU) que introduce un aminoácido cargado en dicha posición, y (d) una cuarta sustitución de aminoácido en una posición seleccionada del grupo que consiste en las posiciones 395 - 403 (numeración EU) que introduce un aminoácido cargado, en donde el aminoácido cargado de (a) tiene la misma carga que el aminoácido cargado de (b) y en donde los aminoácidos cargados de (c) y (d) tienen una carga opuesta de los aminoácidos cargados de (a) y (b). Reivindicación 57: Un ácido nucleico que comprende una secuencia de nucleótidos que codifica el anticuerpo heterodimético de acuerdo con cualquiera de las reivindicaciones 1 - 56. Reivindicación 60: Un método de aumento de la densidad mineral ósea en un sujeto mamífero que comprende la administración del anticuerpo heterodimérico de acuerdo con cualquiera de las reivindicaciones 1 - 56 al sujeto en una cantidad efectiva para incrementar la densidad mineral ósea en el sujeto. Reivindicación 65: Una composición que comprende un anticuerpo heterodimérico o su fragmento y un portador, diluyente o adyuvante farmacéuticamente aceptable, donde el anticuerpo heterodimérico o su fragmento comprende una o más sustituciones en cada uno de los siguientes dominios: un primer dominio CH₃, un segundo dominio CH₃, un dominio CH₁, un dominio CL, un dominio VH y un dominio VL, en donde una o más sustituciones introducen aminoácidos cargados que son electrostáticamente desfavorables para la formación de homodímeros y electrostáticamente favorables para la formación de heterodímeros; en donde menos del 5% del anticuerpo o fragmento en la composición está en forma de agregado después de dos semanas de almacenamiento a aproximadamente 4ºC.
ARP130104306A 2012-11-21 2013-11-21 Inmunoglobulinas heterodimericas AR093584A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261729148P 2012-11-21 2012-11-21
US201361779439P 2013-03-13 2013-03-13

Publications (1)

Publication Number Publication Date
AR093584A1 true AR093584A1 (es) 2015-06-10

Family

ID=49724683

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP130104306A AR093584A1 (es) 2012-11-21 2013-11-21 Inmunoglobulinas heterodimericas

Country Status (22)

Country Link
US (3) US10233237B2 (es)
EP (2) EP3587451A1 (es)
JP (2) JP6585503B2 (es)
KR (3) KR20210080624A (es)
CN (2) CN104968677B (es)
AP (1) AP2015008477A0 (es)
AR (1) AR093584A1 (es)
AU (3) AU2013347963B2 (es)
BR (1) BR112015011518B8 (es)
CA (1) CA2888496C (es)
CL (1) CL2015001369A1 (es)
CR (1) CR20150329A (es)
EA (1) EA201590993A1 (es)
IL (1) IL238642A0 (es)
MX (3) MX376976B (es)
PE (1) PE20150960A1 (es)
PH (1) PH12015501097A1 (es)
SG (2) SG11201503583RA (es)
TN (1) TN2015000196A1 (es)
TW (2) TWI683827B (es)
UY (1) UY35148A (es)
WO (1) WO2014081955A1 (es)

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