RU2016129274A - Канинизированные мышиные антитела к человеческому pd-1 - Google Patents
Канинизированные мышиные антитела к человеческому pd-1 Download PDFInfo
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- RU2016129274A RU2016129274A RU2016129274A RU2016129274A RU2016129274A RU 2016129274 A RU2016129274 A RU 2016129274A RU 2016129274 A RU2016129274 A RU 2016129274A RU 2016129274 A RU2016129274 A RU 2016129274A RU 2016129274 A RU2016129274 A RU 2016129274A
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- 125000003275 alpha amino acid group Chemical group 0.000 claims 15
- 241000282465 Canis Species 0.000 claims 8
- 108020004707 nucleic acids Proteins 0.000 claims 6
- 102000039446 nucleic acids Human genes 0.000 claims 6
- 150000007523 nucleic acids Chemical class 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 239000000427 antigen Substances 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 238000003782 apoptosis assay Methods 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 239000001963 growth medium Substances 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 230000005522 programmed cell death Effects 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 102000009058 Death Domain Receptors Human genes 0.000 claims 1
- 108010049207 Death Domain Receptors Proteins 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000030833 cell death Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 210000002865 immune cell Anatomy 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
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- 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
- C07K16/2803—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 immunoglobulin superfamily
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- 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
- A61P37/04—Immunostimulants
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- 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
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- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
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- 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
-
- 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
- C07K16/2803—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 immunoglobulin superfamily
- C07K16/2818—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 immunoglobulin superfamily against CD28 or CD152
-
- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- 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
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- 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
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- 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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- 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]
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
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- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
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- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (31)
1. Выделенное канинизированное антитело или его антиген-связывающий фрагмент, который специфично связывается с Рецептором 1 Программируемой Клеточной Смерти (PD-1), содержащее тяжелую цепь собачьего IgG и собачью легкую цепь каппа; где собачья легкая цепь каппа содержит три определяющие комплементарность области легкой цепи (CDR): CDR 1 легкой цепи (CDRLl), CDR 2 легкой цепи (CDRL2), и CDR 3 легкой цепи (CDRL3); а тяжелая цепь собачьего IgG содержит три CDR тяжелой цепи: CDR 1 тяжелой цепи (CDRH1), CDR 2 тяжелой цепи (CDRH2) и CDR 3 тяжелой цепи (CDRH3):
(a) где CDRL1 содержит аминокислотную последовательность SEQ ID NO: 20, или консервативно модифицированный вариант SEQ ID NO: 20;
(b) где CDRL2 содержит аминокислотную последовательность SEQ ID NO: 22, или консервативно модифицированный вариант SEQ ID NO: 22;
(c) где CDRL3 содержит аминокислотную последовательность SEQ ID NO: 24, или консервативно модифицированный вариант SEQ ID NO: 24;
(d) где CDRH1 содержит аминокислотную последовательность SEQ ID NO: 14, или консервативно модифицированный вариант SEQ ID NO: 14;
(e) где CDRH2 содержит аминокислотную последовательность SEQ ID NO: 16, или консервативно модифицированный вариант SEQ ID NO: 16;
(f) где CDRH3 содержит аминокислотную последовательность SEQ ID NO: 18, или консервативно модифицированный вариант SEQ ID NO: 18; где антитело и фрагмент связываются с собачьим PD-1 и блокируют связывание собачьего PD-1 с собачьим Лигандом 1 Программируемой Клеточной Смерти (PD-L1).
2. Выделенное канинизированное антитело по п. 1, где CDRL1 содержит аминокислотную последовательность SEQ ID NO: 20.
3. Выделенное канинизированное антитело по п. 1 или 2, где CDRL2 содержит аминокислотную последовательность, включающую SEQ ID NO: 22.
4. Выделенное канинизированное антитело по п. 1, 2, или 3, где CDRL3 содержит аминокислотную последовательность SEQ ID NO: 24.
5. Выделенное канинизированное антитело по п. 1, 2, 3 или 4, где CDRH1 содержит аминокислотную последовательность SEQ ID NO: 14.
6. Выделенное канинизированное антитело по п. 1, 2, 3, 4, или 5, где CDRH2 содержит аминокислотную последовательность, включающую SEQ ID NO: 16.
7. Выделенное канинизированное антитело по п. 1, 2, 3, 4, 5 или 6, где CDRH3 содержит аминокислотную последовательность SEQ ID NO: 18.
8. Выделенное канинизированное антитело по п. 1, 2, 3, 4, 5, 6 или 7, где тяжелая цепь IgG содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 26, консервативно модифицированного варианта SEQ ID NO: 26, SEQ ID NO: 28, консервативно модифицированного варианта SEQ ID NO: 28, SEQ ID NO: 30, и консервативно модифицированного варианта SEQ ID NO: 30.
9. Выделенное канинизированное антитело по п. 1, 2, 3, 4, 5, 6, 7 или 8, где легкая цепь каппа содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 32, консервативно модифицированного варианта SEQ ID NO: 32, SEQ ID NO: 34, и консервативно модифицированного варианта SEQ ID NO: 34.
10. Выделенное канинизированное антитело по п. 9, содержащее аминокислотную последовательность SEQ ID NO: 28 и SEQ ID NO: 34, или консервативно модифицированный вариант SEQ ID NO: 28 и консервативно модифицированный вариант SEQ ID NO: 34.
11. Выделенная нуклеиновая кислота, которая кодирует легкую цепь канинизированного антитела по п. 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10.
12. Выделенная нуклеиновая кислота, которая кодирует тяжелую цепь канинизированного антитела по п. 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10.
13. Выделенная нуклеиновая кислота по п. 11 или 12, которая содержит одну или несколько нуклеотидных последовательностей, выбранных из группы, состоящей из SEQ ID NO: 13, 15, 17, 19, 21, 23, 25, 27, 29, 31 или 33.
14. Выделенная нуклеиновая кислота по п. 13, которая содержит нуклеотидную последовательность SEQ ID NO: 27 или SEQ ID NO: 33.
15. Экспрессирующий вектор, содержащий выделенную нуклеиновую кислоту по п. 11, 12, 13 или 14.
16. Клетка-хозяин, содержащая один или несколько экспрессирующих векторов по п. 15.
17. Фармацевтическая композиция, содержащая антитело или антиген-связывающий фрагмент по п. 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10 и фармацевтически приемлемый носитель или разбавитель.
18. Способ повышения активности иммунной клетки, включающий введение терапевтически эффективного количества фармацевтической композиции по п. 17 объекту, нуждающемуся в этом.
19. Способ по п. 18, где указанный способ применяют для:
a. лечения злокачественного новообразования;
b. лечения инфекции или инфекционного заболевания; или
с. в качестве адъюванта.
20. Способ получения канинизированного антитела или его антиген-связывающего фрагмента, который специфично связывается с PD-1, причем способ включает:
a. культивирование клетки-хозяина по п. 16 в культуральной среде при условиях, в которых экспрессируется нуклеиновая кислота, продуцируя посредством этого полипептид, содержащий вариабельные области легкой цепи и тяжелой цепи; и
b. извлечение полипептидов из клетки-хозяина или из культуральной среды.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361918946P | 2013-12-20 | 2013-12-20 | |
| US201361918847P | 2013-12-20 | 2013-12-20 | |
| US61/918,946 | 2013-12-20 | ||
| US61/918,847 | 2013-12-20 | ||
| US201462030812P | 2014-07-30 | 2014-07-30 | |
| US62/030,812 | 2014-07-30 | ||
| PCT/EP2014/078665 WO2015091914A2 (en) | 2013-12-20 | 2014-12-19 | Caninized murine antibodies to human pd-1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2016129274A true RU2016129274A (ru) | 2018-01-25 |
| RU2676158C1 RU2676158C1 (ru) | 2018-12-26 |
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Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016129113A RU2732604C2 (ru) | 2013-12-20 | 2014-12-19 | Антитела к pd-1 собак |
| RU2016129274A RU2676158C1 (ru) | 2013-12-20 | 2014-12-19 | Канинизированные мышиные антитела к человеческому pd-1 |
| RU2020129387A RU2761663C2 (ru) | 2013-12-20 | 2014-12-19 | Антитела к pd-1 собак |
| RU2016129280A RU2687209C1 (ru) | 2013-12-20 | 2014-12-19 | Собачьи антитела с модифицированными последовательностями ch2-ch3 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016129113A RU2732604C2 (ru) | 2013-12-20 | 2014-12-19 | Антитела к pd-1 собак |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2020129387A RU2761663C2 (ru) | 2013-12-20 | 2014-12-19 | Антитела к pd-1 собак |
| RU2016129280A RU2687209C1 (ru) | 2013-12-20 | 2014-12-19 | Собачьи антитела с модифицированными последовательностями ch2-ch3 |
Country Status (13)
| Country | Link |
|---|---|
| US (9) | US10023636B2 (ru) |
| EP (4) | EP4124624A3 (ru) |
| JP (8) | JP6701079B2 (ru) |
| CN (7) | CN106029697B (ru) |
| AU (6) | AU2014368449C1 (ru) |
| BR (2) | BR112016014284A2 (ru) |
| CA (5) | CA2932515C (ru) |
| DK (1) | DK3083694T3 (ru) |
| ES (1) | ES2969350T3 (ru) |
| FI (1) | FI3083694T3 (ru) |
| PT (1) | PT3083694T (ru) |
| RU (4) | RU2732604C2 (ru) |
| WO (3) | WO2015091910A2 (ru) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106029697B (zh) * | 2013-12-20 | 2021-06-04 | 英特维特国际股份有限公司 | 具有经修饰的ch2-ch3序列的犬抗体 |
| CN112851816B (zh) * | 2014-09-30 | 2024-03-08 | 英特维特国际股份有限公司 | 结合犬pd-l1的pd-l1抗体 |
| BR112017020915A2 (pt) | 2015-04-02 | 2018-07-10 | Intervet Int Bv | ?anticorpo de mamífero isolado ou fragmento de ligação ao antígeno do mesmo, anticorpo caninizado ou fragmento de ligação ao antígeno caninizado do mesmo, anticorpo monoclonal caninizado ou fragmento de ligação ao antígeno do mesmo, ácido nucleico isolado, vetor de expressão, célula hospedeira, peptídeo isolado, proteína de fusão, composição farmacêutica, e, método para diminuir a atividade de uma célula imune? |
| CN108368170B (zh) | 2015-07-13 | 2022-04-15 | 西托姆克斯治疗公司 | 抗pd-1抗体、可活化抗pd-1抗体及其使用方法 |
| EP3322448A4 (en) | 2015-07-16 | 2019-03-06 | Bioxcel Therapeutics, Inc. | NOVEL METHOD FOR THE TREATMENT OF CANCER WITH IMMUNOMODULATION |
| KR20180057637A (ko) * | 2015-08-31 | 2018-05-30 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 개의 암을 치료하기 위한 키메라 aav-항-vegf |
| EP3344656A1 (en) | 2015-09-01 | 2018-07-11 | Agenus Inc. | Anti-pd-1 antibodies and methods of use thereof |
| JP2019500893A (ja) | 2015-11-03 | 2019-01-17 | ヤンセン バイオテツク，インコーポレーテツド | Ｐｄ−１及びｔｉｍ−３に特異的に結合する抗体及びそれらの使用 |
| US11091556B2 (en) | 2015-12-18 | 2021-08-17 | Intervet Inc. | Caninized human antibodies to human IL-4R alpha |
| CA3005696A1 (en) * | 2015-12-18 | 2017-06-22 | Intervet International B.V. | Caninized human antibodies to human and canine il-4r alpha |
| AU2017281830B2 (en) | 2016-06-20 | 2023-04-06 | Kymab Limited | Anti-PD-L1 antibodies |
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