RU2015129762A - ОДНОЛИНКЕРНЫЕ АНТИТЕЛА FabFv И СПОСОБЫ ИХ ПОЛУЧЕНИЯ - Google Patents

ОДНОЛИНКЕРНЫЕ АНТИТЕЛА FabFv И СПОСОБЫ ИХ ПОЛУЧЕНИЯ Download PDF

Info

Publication number
RU2015129762A
RU2015129762A RU2015129762A RU2015129762A RU2015129762A RU 2015129762 A RU2015129762 A RU 2015129762A RU 2015129762 A RU2015129762 A RU 2015129762A RU 2015129762 A RU2015129762 A RU 2015129762A RU 2015129762 A RU2015129762 A RU 2015129762A
Authority
RU
Russia
Prior art keywords
variable domain
seq
sequence
antibody molecule
multispecific
Prior art date
Application number
RU2015129762A
Other languages
English (en)
Other versions
RU2714159C2 (ru
Inventor
Эмма ДЕЙВ
Сэм Филлип Хейвуд
Дэвид Пол Хамфриз
Original Assignee
Юсб Биофарма Спрл
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 Юсб Биофарма Спрл filed Critical Юсб Биофарма Спрл
Publication of RU2015129762A publication Critical patent/RU2015129762A/ru
Application granted granted Critical
Publication of RU2714159C2 publication Critical patent/RU2714159C2/ru

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • 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
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
    • C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
    • C12N15/8257—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon
    • C12N15/8258—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon for the production of oral vaccines (antigens) or immunoglobulins
    • 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
    • C07K2317/50—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
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/624—Disulfide-stabilized antibody (dsFv)
    • 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
    • C07K2317/90—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
    • C07K2319/00—Fusion polypeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurosurgery (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)

Claims (85)

1. Молекула мультиспецифического антитела, содержащая или состоящая из трех полипептидов:
a) полипептидной цепи формулы (I)
(Vxx)nVx-Cx-X-V1 и
b) полипептидной цепи формулы (II)
(Vyy)nVy-Cy;
c) полипептида формулы (III)
V2,
где Vx - вариабельный домен,
Vxx - вариабельный домен,
Сх - константную область,
X - линкер,
V1 - вариабельный домен,
Vy - вариабельный домен,
Vyy - вариабельный домен,
Cy - константную область,
V2 - вариабельный домен,
n независимо равен 0 или 1,
где полипептидная цепь формулы (I) и полипептидная цепь формулы (II) выровнены так, что происходит спаривание константных областей Сх и Cy и спаривание вариабельных доменов Vx и Vy с образованием связывающего домена и, необязательно, дисульфидной связи между V1 и V2, в частности, если дисульфидная связь присутствует.
2. Молекула биспецифического антитела, содержащая или состоящая из трех полипептидов:
a) тяжелой цепи формулы (Ia)
VH-CH1-X-V1 и
b) легкой цепи формулы (IIa)
VL-CL;
c) полипептида формулы (III)
V2,
где VH - вариабельный домен тяжелой цепи,
CH1 - домен 1 константной области тяжелой цепи,
X - линкер,
V1 - вариабельный домен,
VL - вариабельный домен легкой цепи,
CL - константную область легкой цепи,
V2 - вариабельный домен,
где между V1 и V2 необязательно присутствует дисульфидная связь, в частности если дисульфидная связь присутствует.
3. Молекула биспецифического антитела, содержащая или состоящая из трех полипептидов:
a) тяжелой цепи формулы (Ib)
VH-CH1 и
b) легкой цепи формулы (IIb)
VL-CL-X-V2;
c) полипептида формулы (III)
V1,
где VH - вариабельный домен тяжелой цепи,
СН1 - домен 1 константной области тяжелой цепи,
X - линкер,
V1 - вариабельный домен,
VL - вариабельный домен легкой цепи,
CL - константную область легкой цепи,
V2 - вариабельный домен,
где между V1 и V2 необязательно присутствует дисульфидная связь, в частности если дисульфидная связь присутствует.
4. Молекула мультиспецифического антитела по п. 1,
где V1 - вариабельный домен тяжелой цепи, а
V2 - вариабельный домен легкой цепи.
5. Молекула мультиспецифического антитела по 1,
где пара вариабельных доменов V1/V2 связана дисульфидной связью между двумя остатками цистеина, введенными рекомбинантным методом, один в V1 и один в V2,
где положение пары остатков цистеина, введенных рекомбинатным методом, выбрано из группы, состоящей из VH37 и VL95, VH44 и VL100, VH44 и VL105, VH45 и VL87, VH100 и VL50, VH100b и VL49, VH98 и VL46, VH101 и VL46, VH105 и VL43 и VH106 и VL57.
6. Молекула мультиспецифического антитела по п. 1,
где пара вариабельных доменов V1/V2 обладает специфичностью в отношении сывороточного белка-носителя.
7. Молекула мультиспецифического антитела по п. 6,
где V1 содержит
последовательность SEQ ID NO: 87 для CDRH-1,
последовательность SEQ ID NO: 88 для CDRH2 и
последовательность SEQ ID NO: 89 для CDRH-3 и
V2 содержит
последовательность SEQ ID NO: 90 для CDRL-1,
последовательность SEQ ID NO: 91 для CDRL2 и
последовательность SEQ ID NO: 92 для CDRL-3.
8. Молекула мультиспецифического антитела по п. 6,
где V1 содержит
последовательность SEQ ID NO: 93 для CDRH-1,
последовательность SEQ ID NO: 94 для CDRH2 и
последовательность SEQ ID NO: 95 для CDRH-3 и
V2 содержит
последовательность SEQ ID NO: 96 для CDRL-1,
последовательность SEQ ID NO: 97 для CDRL2 и
последовательность SEQ ID NO: 98 для CDRL-3.
9. Молекула мультиспецифического антитела по п. 1,
где X имеет последовательность SEQ ID NO: 78.
10. Молекула биспецифического антитела по п. 3, где X имеет последовательность SEQ ID NO: 103.
11. Полинуклеотид, кодирующий молекулу мультиспецифического или биспецифического антитела по любому из пп. 1-10.
12. Вектор, содержащий полинуклеотид по п. 11.
13. Клетка-хозяин, содержащая вектор или полинуклеотид по п. 12 или 11 соответственно.
14. Клетка-хозяин, содержащая три вектора, где каждый вектор содержит полинуклеотид, кодирующий отдельную полипептидную цепь молекулы мультиспецифического или биспецифического антитела по любому одному из пп. 1-10.
15. Способ, включающий экспрессию молекулы мультиспецифического или биспецифического антитела в клетке-хозяине по п. 13 или 14.
16. Фармацевтическая композиция, содержащая молекулу мультиспецифического или биспецифического антитела по любому из пп. 1-10 и по меньшей мере один наполнитель.
17. Молекула мультиспецифического или биспецифического антитела по любому из пп. 1-10 или фармацевтическая композиция по п. 16 для применения в медицине.
18. Способ лечения пациента, нуждающегося в этом, включающий введение терапевтически эффективного количества молекулы мультиспецифического или биспецифического антитела по любому из пп. 1-10 или фармацевтической композиции по п. 16.
RU2015129762A 2012-12-21 2013-12-20 ОДНОЛИНКЕРНЫЕ АНТИТЕЛА FabFv И СПОСОБЫ ИХ ПОЛУЧЕНИЯ RU2714159C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1223276.5 2012-12-21
GBGB1223276.5A GB201223276D0 (en) 2012-12-21 2012-12-21 Antibodies and methods of producing same
PCT/EP2013/077758 WO2014096390A1 (en) 2012-12-21 2013-12-20 Single linker fabfv antibodies and methods of producing same

Publications (2)

Publication Number Publication Date
RU2015129762A true RU2015129762A (ru) 2017-01-27
RU2714159C2 RU2714159C2 (ru) 2020-02-12

Family

ID=47682492

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2015129762A RU2714159C2 (ru) 2012-12-21 2013-12-20 ОДНОЛИНКЕРНЫЕ АНТИТЕЛА FabFv И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Country Status (10)

Country Link
US (2) US10457748B2 (ru)
EP (1) EP2935336B1 (ru)
JP (1) JP6411362B2 (ru)
CN (1) CN105026431B (ru)
BR (1) BR112015014872B1 (ru)
CA (1) CA2895608C (ru)
ES (1) ES2689470T3 (ru)
GB (1) GB201223276D0 (ru)
RU (1) RU2714159C2 (ru)
WO (1) WO2014096390A1 (ru)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104583239B (zh) 2012-05-10 2018-09-18 生物蛋白有限公司 多特异单克隆抗体
WO2014022540A1 (en) * 2012-08-02 2014-02-06 Regeneron Pharmaceuticals, Inc. Multivalent antigen-binding proteins
GB201223276D0 (en) * 2012-12-21 2013-02-06 Ucb Pharma Sa Antibodies and methods of producing same
GB201409558D0 (en) 2014-05-29 2014-07-16 Ucb Biopharma Sprl Method
GB201411320D0 (en) 2014-06-25 2014-08-06 Ucb Biopharma Sprl Antibody construct
GB201412659D0 (en) 2014-07-16 2014-08-27 Ucb Biopharma Sprl Molecules
GB201412658D0 (en) 2014-07-16 2014-08-27 Ucb Biopharma Sprl Molecules
GB201506869D0 (en) * 2015-04-22 2015-06-03 Ucb Biopharma Sprl Method
GB201506868D0 (en) 2015-04-22 2015-06-03 Ucb Biopharma Sprl Method for protein purification
GB201601077D0 (en) 2016-01-20 2016-03-02 Ucb Biopharma Sprl Antibody molecule
GB201601075D0 (en) 2016-01-20 2016-03-02 Ucb Biopharma Sprl Antibodies molecules
GB201601073D0 (en) 2016-01-20 2016-03-02 Ucb Biopharma Sprl Antibodies
GB201521389D0 (en) 2015-12-03 2016-01-20 Ucb Biopharma Sprl Method
GB201521383D0 (en) 2015-12-03 2016-01-20 Ucb Biopharma Sprl And Ucb Celltech Method
GB201521382D0 (en) 2015-12-03 2016-01-20 Ucb Biopharma Sprl Antibodies
GB201521393D0 (en) 2015-12-03 2016-01-20 Ucb Biopharma Sprl Antibodies
GB201521391D0 (en) 2015-12-03 2016-01-20 Ucb Biopharma Sprl Antibodies
JP7133544B2 (ja) 2016-05-01 2022-09-08 ユーシービー バイオファルマ エスアールエル 親和性を操作した血清タンパク質担体結合ドメイン
GB201621591D0 (en) * 2016-12-19 2017-02-01 Ucb Biopharma Sprl Antibody molecules and method
CA3067835A1 (en) * 2017-06-22 2018-12-27 Apexigen, Inc. Anti-vista antibodies and methods of use
US11965030B2 (en) 2018-12-24 2024-04-23 Sanofi Multispecific binding proteins with mutant fab domains
GB201919062D0 (en) 2019-12-20 2020-02-05 Ucb Biopharma Sprl Antibody
GB201919058D0 (en) 2019-12-20 2020-02-05 Ucb Biopharma Sprl Multi-specific antibodies
GB202001447D0 (en) 2020-02-03 2020-03-18 Ucb Biopharma Sprl Antibodies
US20240024520A1 (en) 2020-03-27 2024-01-25 UCB Biopharma SRL Autonomous knob domain peptides
US20230374148A1 (en) 2020-10-15 2023-11-23 UCB Biopharma SRL Binding molecules that multimerise cd45
JP2023551981A (ja) 2020-12-07 2023-12-13 ユーシービー バイオファルマ エスアールエル 多重特異性抗体及び抗体の組み合わせ
GB202111905D0 (en) 2021-08-19 2021-10-06 UCB Biopharma SRL Antibodies

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4741900A (en) 1982-11-16 1988-05-03 Cytogen Corporation Antibody-metal ion complexes
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
DK336987D0 (da) 1987-07-01 1987-07-01 Novo Industri As Immobiliseringsmetode
GB8719042D0 (en) 1987-08-12 1987-09-16 Parker D Conjugate compounds
GB8720833D0 (en) 1987-09-04 1987-10-14 Celltech Ltd Recombinant dna product
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
EP1892296A1 (en) 1988-09-02 2008-02-27 Dyax Corporation Generation and selection of recombinant varied binding proteins
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
GB8907617D0 (en) 1989-04-05 1989-05-17 Celltech Ltd Drug delivery system
GB8928874D0 (en) 1989-12-21 1990-02-28 Celltech Ltd Humanised antibodies
WO1991010737A1 (en) 1990-01-11 1991-07-25 Molecular Affinities Corporation Production of antibodies using gene libraries
US5780225A (en) 1990-01-12 1998-07-14 Stratagene Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
EP0542810A1 (en) 1990-08-02 1993-05-26 B.R. Centre Limited Methods for the production of proteins with a desired function
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
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
DK0546073T3 (da) 1990-08-29 1998-02-02 Genpharm Int Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5698426A (en) 1990-09-28 1997-12-16 Ixsys, Incorporated Surface expression libraries of heteromeric receptors
ATE164395T1 (de) 1990-12-03 1998-04-15 Genentech Inc Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften
CA2108147C (en) 1991-04-10 2009-01-06 Angray Kang Heterodimeric receptor libraries using phagemids
GB9112536D0 (en) 1991-06-11 1991-07-31 Celltech Ltd Chemical compounds
GB9120467D0 (en) 1991-09-26 1991-11-06 Celltech Ltd Anti-hmfg antibodies and process for their production
WO1993011236A1 (en) 1991-12-02 1993-06-10 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
US5733743A (en) 1992-03-24 1998-03-31 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
US5454806A (en) 1992-11-06 1995-10-03 Terumo Kabushiki Kaisha Medical device
EP0733070A1 (en) 1993-12-08 1996-09-25 Genzyme Corporation Process for generating specific antibodies
DK0744958T3 (da) 1994-01-31 2003-10-20 Univ Boston Polyklonale antistofbiblioteker
FR2716640B1 (fr) 1994-02-28 1996-05-03 Procedes Machines Speciales Dispositif de centrage et de blocage d'une pièce en vue de son rodage à l'aide d'un rodoir à expansion.
US5516637A (en) 1994-06-10 1996-05-14 Dade International Inc. Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage
US5685727A (en) 1995-01-20 1997-11-11 Ocean Design, Inc. Underwater mateable connector
JP2978435B2 (ja) 1996-01-24 1999-11-15 チッソ株式会社 アクリロキシプロピルシランの製造方法
US5980898A (en) 1996-11-14 1999-11-09 The United States Of America As Represented By The U.S. Army Medical Research & Material Command Adjuvant for transcutaneous immunization
GB9625640D0 (en) 1996-12-10 1997-01-29 Celltech Therapeutics Ltd Biological products
CN1224712C (zh) * 1997-06-04 2005-10-26 牛津生物医学（英国）有限公司 载体
DK1049787T3 (da) 1998-01-23 2005-04-04 Vlaams Interuniv Inst Biotech Antistofderivater med flere anvendelsesmuligheder
GB9812545D0 (en) 1998-06-10 1998-08-05 Celltech Therapeutics Ltd Biological products
WO2000002809A1 (en) 1998-07-10 2000-01-20 East/West Industries, Inc. Floor crane with rotatable boom
US20060228364A1 (en) 1999-12-24 2006-10-12 Genentech, Inc. Serum albumin binding peptides for tumor targeting
US6908963B2 (en) 2001-10-09 2005-06-21 Nektar Therapeutics Al, Corporation Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith
ES2374068T3 (es) 2002-12-03 2012-02-13 Ucb Pharma, S.A. Ensayo para identificar células productoras de anticuerpos.
GB0312481D0 (en) 2003-05-30 2003-07-09 Celltech R&D Ltd Antibodies
GB0315450D0 (en) 2003-07-01 2003-08-06 Celltech R&D Ltd Biological products
GB0412181D0 (en) 2004-06-01 2004-06-30 Celltech R&D Ltd Biological products
KR101336204B1 (ko) 2006-08-18 2013-12-03 주식회사 케이티 다시점 비디오에서 전역변이를 이용하여 상이한 시점의 화면들을 압축 또는 복호하는 인코더와 인코딩하는 방법 및디코더와 디코딩하는 방법
GB0619291D0 (en) 2006-09-29 2006-11-08 Ucb Sa Altered antibodies
AU2008282218A1 (en) 2007-07-31 2009-02-05 Medimmune, Llc Multispecific epitope binding proteins and uses thereof
ES2628395T3 (es) 2007-08-15 2017-08-02 Bayer Pharma Aktiengesellschaft Anticuerpo regulado por proteasa
CN101842387B (zh) 2007-09-26 2014-05-07 Ucb医药有限公司 双特异性抗体融合物
WO2010035012A1 (en) 2008-09-26 2010-04-01 Ucb Pharma S.A. Biological products
KR20110124369A (ko) 2009-04-07 2011-11-16 로슈 글리카트 아게 이중특이적 항­ｅｒｂｂ­3／항­ｃ­ｍｅｔ 항체
PT2417156E (pt) 2009-04-07 2015-04-29 Roche Glycart Ag Anticorpos trivalentes, biespecíficos
AU2010252284A1 (en) * 2009-05-27 2011-11-17 F. Hoffmann-La Roche Ag Tri- or tetraspecific antibodies
CN102597298B (zh) 2009-09-09 2014-09-17 耳蜗有限公司 具有通过多个涂层形成的基本上连续的阻挡层的绝缘传导元件
ES2667258T3 (es) * 2009-09-10 2018-05-10 Ucb Biopharma Sprl Anticuerpos multivalentes
GB201005063D0 (en) * 2010-03-25 2010-05-12 Ucb Pharma Sa Biological products
GB0920127D0 (en) * 2009-11-17 2009-12-30 Ucb Pharma Sa Antibodies
JP5758004B2 (ja) * 2010-08-24 2015-08-05 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ジスルフィドによって安定化されたＦｖ断片を含む二重特異性抗体
MX340556B (es) 2010-08-24 2016-07-14 Roche Glycart Ag Anticuerpos biespecificos activables.
MX348738B (es) * 2011-07-13 2017-06-27 Ucb Pharma Sa Cepa huesped bacteriana que expresa dsbc recombinante.
SI2776466T1 (sl) * 2011-11-11 2017-12-29 Ucb Biopharma Sprl Protitelesa, ki se vežejo na albumin in njihovi vezavni fragmenti
UA112203C2 (uk) * 2011-11-11 2016-08-10 Юсб Фарма С.А. Злитий білок біоспецифічного антитіла, який зв'язується з ox40 людини та сироватковим альбуміном людини
GB201223276D0 (en) * 2012-12-21 2013-02-06 Ucb Pharma Sa Antibodies and methods of producing same
GB201506869D0 (en) * 2015-04-22 2015-06-03 Ucb Biopharma Sprl Method
GB201506870D0 (en) * 2015-04-22 2015-06-03 Ucb Biopharma Sprl Method

Also Published As

Publication number Publication date
EP2935336B1 (en) 2018-07-04
JP6411362B2 (ja) 2018-10-24
GB201223276D0 (en) 2013-02-06
JP2016501906A (ja) 2016-01-21
BR112015014872B1 (pt) 2024-02-06
EP2935336A1 (en) 2015-10-28
RU2714159C2 (ru) 2020-02-12
US20160017057A1 (en) 2016-01-21
BR112015014872A2 (ru) 2017-08-15
US10457748B2 (en) 2019-10-29
US11401349B2 (en) 2022-08-02
CN105026431B (zh) 2021-06-25
ES2689470T3 (es) 2018-11-14
WO2014096390A1 (en) 2014-06-26
US20200055959A1 (en) 2020-02-20
CA2895608A1 (en) 2014-06-26
CA2895608C (en) 2021-05-25
CN105026431A (zh) 2015-11-04

Similar Documents

Publication Publication Date Title
RU2015129762A (ru) ОДНОЛИНКЕРНЫЕ АНТИТЕЛА FabFv И СПОСОБЫ ИХ ПОЛУЧЕНИЯ
JP2017529067A5 (ru)
RU2017102193A (ru) Конструкции полиспецифических антител
RU2017102312A (ru) Конструкции мультиспецифичных антител
RU2016106577A (ru) САЙТЫ АНТИТЕЛ, СПЕЦИФИЧНО СВЯЗЫВАЮЩИЕ EGFRvIII
RU2017105120A (ru) Cd3-связывающий домен
HRP20161656T4 (hr) Sredstva za vezanje na cd33
DK2691416T3 (en) ANTIBODY SIMILAR BINDING PROTEIN WITH DOUBLE VARIABLE REGION AND intersecting ORIENTATION OF BINDING REGION
HRP20220111T1 (hr) Protutijela protiv pd-1
JP2016536322A5 (ru)
JP2018529359A5 (ru)
RU2014109039A (ru) Биспецифические антигенсвязывающие молекулы
JP2014158485A5 (ru)
JP2017528117A5 (ru)
RU2014120154A (ru) Стабильные антитела, связывающиеся с несколькими антигенами
RU2017104813A (ru) Молекулы со специфичностью к cd45 и cd79
RU2012143798A (ru) Биспецифические антитела
EA201490020A1 (ru) Растворимые белки для применения в качестве терапевтических средств
US11965030B2 (en) Multispecific binding proteins with mutant fab domains
RU2012131671A (ru) Способ полипептидной модификации для очистки полипептидных мультимеров
RU2016115866A (ru) Мультиспецифические антитела с обменянными доменами и одинаковыми вариабельными доменами легкой цепи
WO2014138449A1 (en) Anti-c-met tandem fc bispecific antibodies
RU2017144098A (ru) Гетеродимеризованный полипептид
RU2008134519A (ru) Связывающие молекулы 3
FI3378535T3 (fi) Alfa-synukleiinin tunnistavia humanisoituja vasta-aineita

Legal Events

Date Code Title Description
PD4A Correction of name of patent owner