JP5953303B2 - 改変された等電点を有する抗体 - Google Patents
改変された等電点を有する抗体 Download PDFInfo
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- JP5953303B2 JP5953303B2 JP2013522017A JP2013522017A JP5953303B2 JP 5953303 B2 JP5953303 B2 JP 5953303B2 JP 2013522017 A JP2013522017 A JP 2013522017A JP 2013522017 A JP2013522017 A JP 2013522017A JP 5953303 B2 JP5953303 B2 JP 5953303B2
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- antibody
- unnatural
- antibodies
- glutamic acid
- amino acid
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- RYYVLZVUVIJVGH-UHFFFAOYSA-N trimethylxanthine Natural products CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
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- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
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- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 1
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 1
- 229960003824 ustekinumab Drugs 0.000 description 1
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- 229940099039 velcade Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
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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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal 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
- C07K2317/50—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
- C07K2317/522—CH1 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
- C07K2317/524—CH2 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
- C07K2317/526—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
- C07K2317/90—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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (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)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36896210P | 2010-07-29 | 2010-07-29 | |
| US36896910P | 2010-07-29 | 2010-07-29 | |
| US61/368,962 | 2010-07-29 | ||
| US61/368,969 | 2010-07-29 | ||
| US39151510P | 2010-10-08 | 2010-10-08 | |
| US39150910P | 2010-10-08 | 2010-10-08 | |
| US61/391,515 | 2010-10-08 | ||
| US61/391,509 | 2010-10-08 | ||
| US201161439263P | 2011-02-03 | 2011-02-03 | |
| US61/439,263 | 2011-02-03 | ||
| PCT/US2011/046041 WO2012016227A2 (en) | 2010-07-29 | 2011-07-29 | Antibodies with modified isoelectric points |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013539361A JP2013539361A (ja) | 2013-10-24 |
| JP2013539361A5 JP2013539361A5 (enExample) | 2014-09-11 |
| JP5953303B2 true JP5953303B2 (ja) | 2016-07-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013522017A Expired - Fee Related JP5953303B2 (ja) | 2010-07-29 | 2011-07-29 | 改変された等電点を有する抗体 |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US8637641B2 (enExample) |
| EP (2) | EP3029066B1 (enExample) |
| JP (1) | JP5953303B2 (enExample) |
| CN (2) | CN105585630B (enExample) |
| AU (2) | AU2011283694B2 (enExample) |
| CA (1) | CA2806252C (enExample) |
| DK (1) | DK3029066T3 (enExample) |
| IL (1) | IL224441B (enExample) |
| WO (1) | WO2012016227A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12084513B2 (en) | 2017-11-14 | 2024-09-10 | Chugai Seiyaku Kabushiki Kaisha | Anti-C1S antibodies and methods of use |
| US12473353B2 (en) | 2019-05-15 | 2025-11-18 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule, a pharmaceutical composition, and a method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
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| GB201203071D0 (en) * | 2012-02-22 | 2012-04-04 | Ucb Pharma Sa | Biological products |
| US9708388B2 (en) | 2012-04-11 | 2017-07-18 | Hoffmann-La Roche Inc. | Antibody light chains |
| JP6774164B2 (ja) | 2012-08-24 | 2020-10-21 | 中外製薬株式会社 | マウスＦｃγＲＩＩ特異的Ｆｃ抗体 |
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| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| WO2014113510A1 (en) | 2013-01-15 | 2014-07-24 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| HK1220466A1 (zh) | 2013-03-14 | 2017-05-05 | Regeneron Pharmaceuticals, Inc. | 爱帕琳融合蛋白和其用途 |
| US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
| US20140294812A1 (en) * | 2013-03-15 | 2014-10-02 | Xencor, Inc. | Fc variants that improve fcrn binding and/or increase antibody half-life |
| JP6594855B2 (ja) * | 2013-03-15 | 2019-10-23 | ゼンコア インコーポレイテッド | ヘテロ二量体タンパク質 |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| EP3421495A3 (en) | 2013-03-15 | 2019-05-15 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| CA2908350C (en) | 2013-04-02 | 2023-08-08 | Futa Mimoto | Fc region variant |
| CN105764922B (zh) | 2013-09-27 | 2020-07-17 | 中外制药株式会社 | 多肽异源多聚体的制备方法 |
| MX377716B (es) | 2013-11-20 | 2025-03-11 | Regeneron Pharma | Moduladores de aplnr y usos de estos. |
| MX385936B (es) | 2014-03-28 | 2025-03-11 | Xencor Inc | Anticuerpos biespecíficos que se unen a cd38 y cd3. |
| ES2869459T3 (es) | 2014-05-16 | 2021-10-25 | Medimmune Llc | Moléculas con unión a receptor de fc de neonato alterada que tiene propiedades terapéuticas y de diagnóstico potenciadas |
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| MX2016014355A (es) * | 2014-06-12 | 2017-01-27 | Hoffmann La Roche | Metodo para seleccionar anticuerpos con interaccion del receptor de fc neonatal (fcrn) modificado. |
| JO3537B1 (ar) * | 2014-07-10 | 2020-07-05 | Bioarctic Neuroscience Ab | أجسام مضادة لييفية أولية لاميلويد بيتا الببتيد ab المحسنة |
| HRP20201756T8 (hr) * | 2014-11-21 | 2021-08-20 | Bristol-Myers Squibb Company | Antitijela koja sadrže modificirane regije teškog lanca |
| TWI711630B (zh) | 2014-11-21 | 2020-12-01 | 美商必治妥美雅史谷比公司 | 抗ｃｄ７３抗體及其用途 |
| HRP20211273T1 (hr) | 2014-11-26 | 2021-11-12 | Xencor, Inc. | Heterodimerna protutijela koja vežu cd3 i cd20 |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| MY181199A (en) | 2014-12-19 | 2020-12-21 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
| CN107108729A (zh) | 2015-02-05 | 2017-08-29 | 中外制药株式会社 | 包含离子浓度依赖性的抗原结合结构域的抗体，fc区变体，il‑8‑结合抗体，及其应用 |
| WO2016141387A1 (en) | 2015-03-05 | 2016-09-09 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| WO2016159213A1 (ja) | 2015-04-01 | 2016-10-06 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
| CA2988115A1 (en) | 2015-06-03 | 2016-12-08 | Bristol-Myers Squibb Company | Anti-gitr antibodies for cancer diagnostics |
| PH12018500386B1 (en) | 2015-09-18 | 2024-01-05 | Chugai Pharmaceutical Co Ltd | Il-8-binding antibodies and uses thereof |
| CN116987187A (zh) | 2015-09-23 | 2023-11-03 | 豪夫迈·罗氏有限公司 | 抗-vegf抗体的优化的变体 |
| JP6983776B2 (ja) | 2015-11-19 | 2021-12-17 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | グルココルチコイド誘発腫瘍壊死因子受容体（ｇｉｔｒ）に対する抗体およびその使用 |
| JP7058219B2 (ja) | 2015-12-07 | 2022-04-21 | ゼンコア インコーポレイテッド | Ｃｄ３及びｐｓｍａに結合するヘテロ二量体抗体 |
| WO2017104783A1 (en) | 2015-12-18 | 2017-06-22 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| WO2017110981A1 (en) | 2015-12-25 | 2017-06-29 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
| CA3004288C (en) | 2015-12-28 | 2025-05-27 | Chugai Seiyaku Kabushiki Kaisha | METHOD FOR PROMOTING THE CLEARANCE EFFICIENCY OF A POLYPEPTIDE CONTAINING THE FC REGION |
| FI3468586T3 (fi) | 2016-06-14 | 2024-10-29 | Xencor Inc | Bispesifisiä immuuniaktivaatiota vapauttavia vasta-aineita |
| EA201990017A1 (ru) | 2016-06-17 | 2019-07-31 | Чугаи Сейяку Кабусики Кайся | Антитела к миостатину и способы их применения |
| EP3475304B1 (en) | 2016-06-28 | 2022-03-23 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| JP6527643B2 (ja) | 2016-08-05 | 2019-06-05 | 中外製薬株式会社 | Ｉｌ−８関連疾患の治療用又は予防用組成物 |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
| CA3040504A1 (en) | 2016-10-14 | 2018-04-19 | Xencor, Inc. | Il15/il15ra heterodimeric fc-fusion proteins |
| KR20200006115A (ko) | 2017-05-16 | 2020-01-17 | 브리스톨-마이어스 스큅 컴퍼니 | 항-gitr 효능제 항체에 의한 암의 치료 |
| MA49517A (fr) | 2017-06-30 | 2020-05-06 | Xencor Inc | Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène |
| WO2019094637A1 (en) | 2017-11-08 | 2019-05-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| KR102722731B1 (ko) | 2017-12-19 | 2024-10-25 | 젠코어 인코포레이티드 | 조작된 il-2 fc 융합 단백질 |
| IL277375B2 (en) | 2018-03-15 | 2025-08-01 | Chugai Pharmaceutical Co Ltd | Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use |
| CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
| CA3097741A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
| JP2021521784A (ja) | 2018-04-18 | 2021-08-30 | ゼンコア インコーポレイテッド | ＩＬ−１５／ＩＬ−１５ＲａＦｃ融合タンパク質とＰＤ−１抗原結合ドメインを含むＰＤ−１標的化ヘテロダイマー融合タンパク質およびそれらの使用 |
| EP3781597A1 (en) | 2018-04-18 | 2021-02-24 | Xencor, Inc. | Lag-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and lag-3 antigen binding domains |
| TWI848953B (zh) | 2018-06-09 | 2024-07-21 | 德商百靈佳殷格翰國際股份有限公司 | 針對癌症治療之多特異性結合蛋白 |
| PE20211091A1 (es) | 2018-07-02 | 2021-06-14 | Amgen Inc | Proteina de union al antigeno anti-steap1 |
| AU2019326407A1 (en) * | 2018-08-21 | 2021-02-18 | Bioatla, Inc. | Conditionally active proteins with pH selectivity |
| SG11202103192RA (en) | 2018-10-03 | 2021-04-29 | Xencor Inc | Il-12 heterodimeric fc-fusion proteins |
| CA3116188A1 (en) | 2018-10-12 | 2020-04-16 | Xencor, Inc. | Pd-1 targeted il-15/il-15ralpha fc fusion proteins and uses in combination therapies thereof |
| MX2021010390A (es) | 2019-03-01 | 2021-11-17 | Xencor Inc | Anticuerpos heterodimericos que se unen a enpp3 y cd3. |
| CA3136398A1 (en) | 2019-04-10 | 2020-10-15 | Chugai Seiyaku Kabushiki Kaisha | Method for purifying fc region-modified antibody |
| AU2020279112A1 (en) | 2019-05-17 | 2021-12-02 | Xencor, Inc. | IL-7-Fc-fusion proteins |
| US20210102002A1 (en) | 2019-08-06 | 2021-04-08 | Xencor, Inc. | HETERODIMERIC IgG-LIKE BISPECIFIC ANTIBODIES |
| WO2021122733A1 (en) | 2019-12-18 | 2021-06-24 | F. Hoffmann-La Roche Ag | Bispecific anti-ccl2 antibodies |
| UA128549C2 (uk) | 2019-12-27 | 2024-08-07 | Чугаі Сейяку Кабусікі Кайся | Антитіло до ctla-4 та його застосування |
| US20220106403A1 (en) | 2020-05-14 | 2022-04-07 | Xencor, Inc. | Heterodimeric antibodies that bind msln and cd3 |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| WO2022040482A1 (en) | 2020-08-19 | 2022-02-24 | Xencor, Inc. | Anti-cd28 and/or anti-b7h3 compositions |
| JP7731359B2 (ja) | 2020-08-28 | 2025-08-29 | 中外製薬株式会社 | ヘテロ二量体Ｆｃポリペプチド |
| WO2022081886A1 (en) | 2020-10-14 | 2022-04-21 | Xencor, Inc. | Bispecific antibodies that bind pd-l1 and cd28 |
| CN117157319A (zh) | 2021-03-09 | 2023-12-01 | Xencor股份有限公司 | 结合cd3和cldn6的异二聚抗体 |
| KR20230154311A (ko) | 2021-03-10 | 2023-11-07 | 젠코어 인코포레이티드 | Cd3 및 gpc3에 결합하는 이종이량체 항체 |
| AR125344A1 (es) * | 2021-04-15 | 2023-07-05 | Chugai Pharmaceutical Co Ltd | Anticuerpo anti-c1s |
| CA3221735A1 (en) | 2021-06-18 | 2022-12-22 | F. Hoffmann-La Roche Ag | Bispecific anti-ccl2 antibodies |
| JP7472405B2 (ja) | 2021-06-25 | 2024-04-22 | 中外製薬株式会社 | 抗ｃｔｌａ－４抗体 |
| TWI864408B (zh) | 2021-06-25 | 2024-12-01 | 日商中外製藥股份有限公司 | 抗ctla-4抗體的用途 |
| WO2023010021A1 (en) | 2021-07-27 | 2023-02-02 | Xencor, Inc. | Il-18-fc fusion proteins |
| US20240360233A1 (en) | 2021-08-27 | 2024-10-31 | Board Of Regents, The University Of Texas System | Anti-tslpr (crlf2) antibodies |
| WO2023049922A1 (en) | 2021-09-27 | 2023-03-30 | Xencor, Inc. | B-cell maturation antigen (bcma) binding domain compositions |
| US20230151095A1 (en) | 2021-11-12 | 2023-05-18 | Xencor, Inc. | Bispecific antibodies that bind to b7h3 and nkg2d |
| MX2024010339A (es) | 2022-02-23 | 2024-09-30 | Xencor Inc | Anticuerpos anti-cd28 x anti-psma. |
| WO2023164627A1 (en) | 2022-02-24 | 2023-08-31 | Xencor, Inc. | Anti-cd28 x anti-msln antibodies |
| EP4482865A1 (en) | 2022-02-24 | 2025-01-01 | Xencor, Inc. | Anti-cd28 x anti-trop2 antibodies |
| US20240025968A1 (en) | 2022-04-07 | 2024-01-25 | Xencor, Inc. | LAG-3 TARGETED HETERODIMERIC FUSION PROTEINS CONTAINING IL-15/IL-15RA Fc-FUSION PROTEINS AND LAG-3 ANTIGEN BINDING DOMAINS |
| US20230383012A1 (en) | 2022-04-13 | 2023-11-30 | Xencor, Inc. | Antibodies that bind pd-l1, pd-l2, and/or cd28 |
| JP7753313B2 (ja) * | 2022-10-18 | 2025-10-14 | 中外製薬株式会社 | 抗Ｃ１ｓ抗体の使用 |
| AU2023367039A1 (en) | 2022-10-25 | 2025-05-15 | Ablexis, Llc | Anti-cd3 antibodies |
| WO2024102636A1 (en) | 2022-11-07 | 2024-05-16 | Xencor, Inc. | Bispecific antibodies that bind to b7h3 and mica/b |
| US20240166705A1 (en) | 2022-11-07 | 2024-05-23 | Xencor, Inc. | Il18-fc fusion proteins |
| WO2024107731A2 (en) | 2022-11-14 | 2024-05-23 | Ablexis, Llc | Anti-pd-l1 antibodies |
| KR20250173599A (ko) | 2023-03-14 | 2025-12-10 | 젠코어 인코포레이티드 | 항-cd28 조성물 |
| US20250084179A1 (en) | 2023-04-14 | 2025-03-13 | Xencor, Inc. | Anti-cd28 x anti-trop2 antibodies |
| US20250084186A1 (en) | 2023-04-14 | 2025-03-13 | Xencor, Inc. | Anti-cd28 x anti-enpp3 antibodies |
| WO2024227002A2 (en) | 2023-04-28 | 2024-10-31 | Xencor, Inc. | Orthogonal multimeric proteins |
| TW202525853A (zh) | 2023-08-28 | 2025-07-01 | 美商山可爾股份有限公司 | 抗ｃｄ２０ｘ抗ｃｄ２８組合療法 |
| WO2025085672A1 (en) | 2023-10-17 | 2025-04-24 | Xencor, Inc. | Bispecific antibodies that bind to nkp46 and mica/b |
| WO2025085447A1 (en) | 2023-10-17 | 2025-04-24 | Xencor, Inc. | Pd-1 targeted il18-fc fusion proteins |
| WO2025090973A2 (en) | 2023-10-27 | 2025-05-01 | Xencor, Inc. | Anti-trop2 x anti-pdl1 x anti-cd28 antibodies |
| WO2025111585A1 (en) * | 2023-11-22 | 2025-05-30 | Cantai Therapeutics Inc. | Engineered bispecific molecules and methods of use |
| WO2025252840A1 (en) * | 2024-06-04 | 2025-12-11 | Technische Universitaet Muenchen, In Vertretung Des Freistaates Bayern | Half-life modulation by a tag comprising at least one constant domain of an immunoglobulin light chain |
Family Cites Families (294)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| CU22545A1 (es) | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
| US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
| JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
| JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
| JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
| EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
| US4364935A (en) | 1979-12-04 | 1982-12-21 | Ortho Pharmaceutical Corporation | Monoclonal antibody to a human prothymocyte antigen and methods of preparing same |
| WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
| US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
| US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
| US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
| JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4753894A (en) | 1984-02-08 | 1988-06-28 | Cetus Corporation | Monoclonal anti-human breast cancer antibodies |
| US4943533A (en) | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
| US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| WO1987005330A1 (en) | 1986-03-07 | 1987-09-11 | Michel Louis Eugene Bergh | Method for enhancing glycoprotein stability |
| WO1987006265A1 (fr) | 1986-04-17 | 1987-10-22 | Kyowa Hakko Kogyo Co., Ltd. | Nouveaux composes dc-88a et dc-89a1, et procede pour leur preparation |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US4880935A (en) | 1986-07-11 | 1989-11-14 | Icrf (Patents) Limited | Heterobifunctional linking agents derived from N-succinimido-dithio-alpha methyl-methylene-benzoates |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
| US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
| US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
| WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| IL89220A (en) | 1988-02-11 | 1994-02-27 | Bristol Myers Squibb Co | Anthracycline immunoconjugates, their production and pharmaceutical compositions containing them |
| US5084468A (en) | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| JP2598116B2 (ja) | 1988-12-28 | 1997-04-09 | 協和醗酵工業株式会社 | 新規物質ｄｃ１１３ |
| US5187186A (en) | 1989-07-03 | 1993-02-16 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives |
| JP2510335B2 (ja) | 1989-07-03 | 1996-06-26 | 協和醗酵工業株式会社 | Ｄｃ―８８ａ誘導体 |
| CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| EP0530225A4 (en) | 1990-05-07 | 1993-09-22 | Scripps Clinic And Research Foundation | Intermediates in the formation of the calicheamicin and esperamicin oligosaccharides |
| US5968509A (en) | 1990-10-05 | 1999-10-19 | Btp International Limited | Antibodies with binding affinity for the CD3 antigen |
| WO1992015683A1 (en) | 1991-03-06 | 1992-09-17 | MERCK Patent Gesellschaft mit beschränkter Haftung | Humanized and chimeric monoclonal antibodies |
| EP0940468A1 (en) | 1991-06-14 | 1999-09-08 | Genentech, Inc. | Humanized antibody variable domain |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| US5264586A (en) | 1991-07-17 | 1993-11-23 | The Scripps Research Institute | Analogs of calicheamicin gamma1I, method of making and using the same |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| GB9206422D0 (en) | 1992-03-24 | 1992-05-06 | Bolt Sarah L | Antibody preparation |
| ES2149768T3 (es) | 1992-03-25 | 2000-11-16 | Immunogen Inc | Conjugados de agentes enlazantes de celulas derivados de cc-1065. |
| ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
| US6329507B1 (en) | 1992-08-21 | 2001-12-11 | The Dow Chemical Company | Dimer and multimer forms of single chain polypeptides |
| US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
| US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
| DK0672142T3 (da) | 1992-12-04 | 2001-06-18 | Medical Res Council | Multivalente og multispecifikke bindingsproteiner samt fremstilling og anvendelse af disse |
| CA2117477C (en) | 1992-12-11 | 2001-06-12 | Peter S. Mezes | Multivalent single chain antibodies |
| US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| US5767237A (en) | 1993-10-01 | 1998-06-16 | Teikoku Hormone Mfg. Co., Ltd. | Peptide derivatives |
| GB9401182D0 (en) | 1994-01-21 | 1994-03-16 | Inst Of Cancer The Research | Antibodies to EGF receptor and their antitumour effect |
| ATE271557T1 (de) | 1994-04-22 | 2004-08-15 | Kyowa Hakko Kogyo Kk | Dc-89 derivat |
| JPH07309761A (ja) | 1994-05-20 | 1995-11-28 | Kyowa Hakko Kogyo Co Ltd | デュオカルマイシン誘導体の安定化法 |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| US5945311A (en) | 1994-06-03 | 1999-08-31 | GSF--Forschungszentrumfur Umweltund Gesundheit | Method for producing heterologous bi-specific antibodies |
| US5550246A (en) | 1994-09-07 | 1996-08-27 | The Scripps Research Institute | Calicheamicin mimics |
| US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
| US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5739277A (en) * | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
| EP0831880A4 (en) | 1995-06-07 | 2004-12-01 | Imclone Systems Inc | ANTIBODIES AND FRAGMENTS OF ANTIBODIES INHIBITING TUMOR GROWTH |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| US7696338B2 (en) | 1995-10-30 | 2010-04-13 | The United States Of America As Represented By The Department Of Health And Human Services | Immunotoxin fusion proteins and means for expression thereof |
| JP2000503639A (ja) | 1995-12-22 | 2000-03-28 | ブリストル―マイヤーズ スクイブ カンパニー | 分枝ヒドラゾンのリンカー類 |
| AU751659B2 (en) | 1997-05-02 | 2002-08-22 | Genentech Inc. | A method for making multispecific antibodies having heteromultimeric and common components |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| ATE283364T1 (de) | 1998-01-23 | 2004-12-15 | Vlaams Interuniv Inst Biotech | Mehrzweck-antikörperderivate |
| DK1071700T3 (da) | 1998-04-20 | 2010-06-07 | Glycart Biotechnology Ag | Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet |
| JP4169478B2 (ja) | 1998-04-21 | 2008-10-22 | マイクロメット アーゲー | Ｃｄ１９×ｃｄ３特異的ポリペプチドおよびその使用 |
| US6455677B1 (en) | 1998-04-30 | 2002-09-24 | Boehringer Ingelheim International Gmbh | FAPα-specific antibody with improved producibility |
| WO1999066951A2 (en) | 1998-06-22 | 1999-12-29 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
| GB9815909D0 (en) | 1998-07-21 | 1998-09-16 | Btg Int Ltd | Antibody preparation |
| US6723538B2 (en) | 1999-03-11 | 2004-04-20 | Micromet Ag | Bispecific antibody and chemokine receptor constructs |
| AU3672800A (en) | 1999-04-09 | 2000-11-14 | Kyowa Hakko Kogyo Co. Ltd. | Method for controlling the activity of immunologically functional molecule |
| US6939545B2 (en) | 1999-04-28 | 2005-09-06 | Genetics Institute, Llc | Composition and method for treating inflammatory disorders |
| US7303749B1 (en) | 1999-10-01 | 2007-12-04 | Immunogen Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| AU775373B2 (en) | 1999-10-01 | 2004-07-29 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| EP1229125A4 (en) | 1999-10-19 | 2005-06-01 | Kyowa Hakko Kogyo Kk | PROCESS FOR PREPARING A POLYPEPTIDE |
| US6716410B1 (en) | 1999-10-26 | 2004-04-06 | The Regents Of The University Of California | Reagents and methods for diagnosing, imaging and treating atherosclerotic disease |
| HUP0204142A3 (en) | 2000-02-25 | 2004-12-28 | Univ Durham | Anti-egfrviii scfv-antibodies with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof |
| US20010035606A1 (en) | 2000-03-28 | 2001-11-01 | Schoen Alan H. | Set of blocks for packing a cube |
| AU5943201A (en) | 2000-05-03 | 2001-11-12 | Amgen Inc | Modified peptides as therapeutic agents |
| WO2001088138A1 (en) | 2000-05-19 | 2001-11-22 | Scancell Limited | Humanised antibodies to the epidermal growth factor receptor |
| WO2001090192A2 (en) | 2000-05-24 | 2001-11-29 | Imclone Systems Incorporated | Bispecific immunoglobulin-like antigen binding proteins and method of production |
| WO2002008293A2 (en) | 2000-07-25 | 2002-01-31 | Immunomedics Inc. | Multivalent target binding protein |
| US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
| DE10043437A1 (de) | 2000-09-04 | 2002-03-28 | Horst Lindhofer | Verwendung von trifunktionellen bispezifischen und trispezifischen Antikörpern zur Behandlung von malignem Aszites |
| MXPA00009407A (es) | 2000-09-26 | 2004-12-08 | Mexicano Inst Petrol | Procedimiento para la preparacion de un catalizador monometalico de tipo zeolitico para la obtencion de gasolinas de alto octando mediante reformacion de naftas. |
| HU231090B1 (hu) | 2000-10-06 | 2020-07-28 | Kyowa Kirin Co., Ltd. | Antitest-kompozíciót termelő sejt |
| WO2002030954A1 (en) | 2000-10-06 | 2002-04-18 | Kyowa Hakko Kogyo Co., Ltd. | Method of purifying antibody |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| AU2002251913A1 (en) | 2001-02-02 | 2002-08-19 | Millennium Pharmaceuticals, Inc. | Hybrid antibodies and uses thereof |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| JP2005500018A (ja) | 2001-04-02 | 2005-01-06 | アイデック ファーマスーティカルズ コーポレイション | ＧｎＴＩＩＩと同時発現する組換え抗体 |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| CN1463270A (zh) | 2001-05-31 | 2003-12-24 | 梅达莱克斯公司 | 细胞毒素、其有用的前体药物、连接基团和稳定剂 |
| US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
| BRPI0210405B8 (pt) | 2001-06-13 | 2021-05-25 | Genmab As | anticorpo monoclonal humano, molécula biespecífica, método in vitro para inibir o crescimento de uma célula expressando egfr, para induzir a citólise de uma célula expressando egfr, e para detectar a presença de antígeno egfr ou uma célula expressando egfr em uma amostra, e, vetor de expressão |
| EP1411983A4 (en) | 2001-06-26 | 2006-06-21 | Imclone Systems Inc | BISPECIFIC ANTIBODIES BINDING TO VEGF RECEPTORS |
| ATE430580T1 (de) | 2001-10-25 | 2009-05-15 | Genentech Inc | Glycoprotein-zusammensetzungen |
| US20080219974A1 (en) | 2002-03-01 | 2008-09-11 | Bernett Matthew J | Optimized antibodies that target hm1.24 |
| US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
| US7332580B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The University Of California | Bispecific single chain Fv antibody molecules and methods of use thereof |
| WO2005056606A2 (en) | 2003-12-03 | 2005-06-23 | Xencor, Inc | Optimized antibodies that target the epidermal growth factor receptor |
| SI2357006T1 (sl) | 2002-07-31 | 2016-01-29 | Seattle Genetics, Inc. | Konjugati zdravil in njihova uporaba za zdravljenje raka, avtoimunske bolezni ali infekcijske bolezni |
| US8946387B2 (en) | 2002-08-14 | 2015-02-03 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
| EP1391213A1 (en) | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
| US20060235208A1 (en) | 2002-09-27 | 2006-10-19 | Xencor, Inc. | Fc variants with optimized properties |
| US7820166B2 (en) | 2002-10-11 | 2010-10-26 | Micromet Ag | Potent T cell modulating molecules |
| AU2003282624A1 (en) | 2002-11-14 | 2004-06-03 | Syntarga B.V. | Prodrugs built as multiple self-elimination-release spacers |
| BRPI0316282B8 (pt) | 2002-11-15 | 2021-05-25 | Genmab As | anticorpo humano isolado monoclonal, composição, imunoconjugado, molécula biespecífica ou multiespecífica, método e conjunto de diagnóstico para detectar a presença de antígeno cd25 ou uma célula que expressa cd25, e, vetor de expressão |
| CN103833854B (zh) | 2002-12-16 | 2017-12-12 | 健泰科生物技术公司 | 免疫球蛋白变体及其用途 |
| US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
| US7610156B2 (en) | 2003-03-31 | 2009-10-27 | Xencor, Inc. | Methods for rational pegylation of proteins |
| US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
| AU2004240541B2 (en) | 2003-05-20 | 2009-08-20 | Immunogen, Inc. | Improved cytotoxic agents comprising new maytansinoids |
| EP1629012B1 (en) | 2003-05-31 | 2018-11-28 | Amgen Research (Munich) GmbH | Pharmaceutical compositions comprising bispecific anti-cd3, anti-cd19 antibody constructs for the treatment of b-cell related disorders |
| KR20060015602A (ko) | 2003-05-31 | 2006-02-17 | 마이크로메트 에이지 | ＥｐＣＡＭ 에 대한 이중 특이성 항체를 포함하는약학조성물 |
| US7888134B2 (en) | 2003-06-05 | 2011-02-15 | Oakland University | Immunosensors: scFv-linker design for surface immobilization |
| US20060134105A1 (en) | 2004-10-21 | 2006-06-22 | Xencor, Inc. | IgG immunoglobulin variants with optimized effector function |
| US20150071948A1 (en) | 2003-09-26 | 2015-03-12 | Gregory Alan Lazar | Novel immunoglobulin variants |
| US20050176028A1 (en) | 2003-10-16 | 2005-08-11 | Robert Hofmeister | Deimmunized binding molecules to CD3 |
| BR122018071808B8 (pt) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugado |
| AU2004297616B2 (en) | 2003-12-04 | 2008-12-18 | Xencor, Inc. | Methods of generating variant proteins with increased host string content and compositions thereof |
| CN1922210A (zh) | 2003-12-19 | 2007-02-28 | 健泰科生物技术公司 | 可用作治疗剂的单价抗体片段 |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| WO2005092925A2 (en) * | 2004-03-24 | 2005-10-06 | Xencor, Inc. | Immunoglobulin variants outside the fc region |
| RU2402548C2 (ru) | 2004-05-19 | 2010-10-27 | Медарекс, Инк. | Химические линкеры и их конъюгаты |
| MXPA06013413A (es) | 2004-05-19 | 2007-01-23 | Medarex Inc | Enlazadores quimicos y conjugados de los mismos. |
| EA010350B1 (ru) | 2004-06-03 | 2008-08-29 | Новиммун С.А. | Антитела против cd3 и способы их применения |
| WO2006004910A2 (en) | 2004-06-28 | 2006-01-12 | Transtarget Inc. | Improved bispecific antibodies |
| EP1786918A4 (en) | 2004-07-17 | 2009-02-11 | Imclone Systems Inc | NEW BISPECIFIC ANTIBODY TETRAVALENT |
| KR101247908B1 (ko) | 2004-09-02 | 2013-03-26 | 제넨테크, 인크. | 항-ｆｃ-감마 ｒｉｉｂ 수용체 항체 및 그의 용도 |
| CN101065151B (zh) | 2004-09-23 | 2014-12-10 | 健泰科生物技术公司 | 半胱氨酸改造的抗体和偶联物 |
| AU2005289685B2 (en) | 2004-09-24 | 2009-07-16 | Amgen Inc. | Modified Fc molecules |
| US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
| US8066989B2 (en) | 2004-11-30 | 2011-11-29 | Trion Pharma Gmbh | Method of treating tumor growth and metastasis by using trifunctional antibodies to reduce the risk for GvHD in allogeneic antitumor cell therapy |
| PL1699826T3 (pl) | 2005-01-05 | 2009-08-31 | F Star Biotechnologische Forschungs Und Entw M B H | Syntetyczne domeny immunoglobulinowe o właściwościach wiążących modyfikowane w regionach cząsteczki różnych od regionów determinujących komplementarność |
| JP4986633B2 (ja) | 2005-01-12 | 2012-07-25 | 協和発酵キリン株式会社 | 安定化されたヒトＩｇＧ２およびＩｇＧ３抗体 |
| EP3050963B1 (en) | 2005-03-31 | 2019-09-18 | Chugai Seiyaku Kabushiki Kaisha | Process for production of polypeptide by regulation of assembly |
| US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
| US9284375B2 (en) | 2005-04-15 | 2016-03-15 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
| US8309690B2 (en) | 2005-07-01 | 2012-11-13 | Medimmune, Llc | Integrated approach for generating multidomain protein therapeutics |
| ATE501277T1 (de) | 2005-07-01 | 2011-03-15 | Dako Denmark As | Monomere und polymere linker zur konjugierung von biologischen molekülen und anderen stoffen |
| SI1912675T1 (sl) | 2005-07-25 | 2014-07-31 | Emergent Product Development Seattle, Llc | zmanjšanje števila celic B z uporabo molekul, ki se specifično vežejo na CD37 in CD20 |
| WO2007014238A2 (en) | 2005-07-25 | 2007-02-01 | Trubion Pharmaceuticals, Inc. | Single dose use of cd20-specific binding molecules |
| US8158590B2 (en) | 2005-08-05 | 2012-04-17 | Syntarga B.V. | Triazole-containing releasable linkers, conjugates thereof, and methods of preparation |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| DK1931709T3 (en) | 2005-10-03 | 2017-03-13 | Xencor Inc | FC VARIETIES WITH OPTIMIZED FC RECEPTOR BINDING PROPERTIES |
| DK1940881T3 (en) | 2005-10-11 | 2017-02-20 | Amgen Res Munich Gmbh | COMPOSITIONS WITH ARTICLE CROSS-SPECIFIC ANTIBODIES AND APPLICATIONS THEREOF |
| KR20080073293A (ko) | 2005-10-14 | 2008-08-08 | 메디뮨 엘엘씨 | 항체 라이브러리의 세포 디스플레이 |
| WO2007047829A2 (en) | 2005-10-19 | 2007-04-26 | Laboratoires Serono S.A. | Novel heterodimeric proteins and uses thereof |
| TW200732350A (en) | 2005-10-21 | 2007-09-01 | Amgen Inc | Methods for generating monovalent IgG |
| WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| CA2627446A1 (en) | 2005-11-21 | 2007-05-31 | Laboratoires Serono S.A. | Compositions and methods of producing hybrid antigen binding molecules and uses thereof |
| JP2009521474A (ja) | 2005-12-21 | 2009-06-04 | メディミューン，エルエルシー | ＥｐｈＡ２ＢｉＴＥ分子およびその使用 |
| JP5346589B2 (ja) | 2006-02-02 | 2013-11-20 | シンタルガ・ビーブイ | 水溶性ｃｃ−１０６５類似体及びその接合体 |
| EP1820513A1 (en) | 2006-02-15 | 2007-08-22 | Trion Pharma Gmbh | Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies |
| EP1829895A1 (en) | 2006-03-03 | 2007-09-05 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Bispecific molecule binding TLR9 and CD32 and comprising a T cell epitope for treatment of allergies |
| AU2007227292B2 (en) | 2006-03-17 | 2012-04-12 | Biogen Ma Inc. | Stabilized polypeptide compositions |
| CA2646965C (en) | 2006-03-24 | 2016-06-21 | Jonathan H. Davis | Engineered heterodimeric protein domains |
| CA2647846C (en) | 2006-03-31 | 2016-06-21 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
| CN105177091A (zh) | 2006-03-31 | 2015-12-23 | 中外制药株式会社 | 用于纯化双特异性抗体的抗体修饰方法 |
| EP2007423A2 (en) | 2006-04-05 | 2008-12-31 | Pfizer Products Incorporated | Ctla4 antibody combination therapy |
| US20090182127A1 (en) | 2006-06-22 | 2009-07-16 | Novo Nordisk A/S | Production of Bispecific Antibodies |
| AT503902B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von immunglobulinen |
| AT503861B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von t-zell-rezeptoren |
| AT503889B1 (de) | 2006-07-05 | 2011-12-15 | Star Biotechnologische Forschungs Und Entwicklungsges M B H F | Multivalente immunglobuline |
| AU2007303572A1 (en) | 2006-10-02 | 2008-04-10 | Sea Lane Biotechnologies, Llc | Design and construction of diverse synthetic peptide and polypeptide libraries |
| JP5779350B2 (ja) | 2007-03-27 | 2015-09-16 | シー レーン バイオテクノロジーズ， エルエルシー | 抗体代替軽鎖配列を含む構築物およびライブラリー |
| EP1975178A1 (en) | 2007-03-30 | 2008-10-01 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Transcytotic modular antibody |
| HUE040467T2 (hu) | 2007-04-03 | 2019-03-28 | Amgen Res Munich Gmbh | Keresztfaj-specifikus kötõdomén |
| CA2682626A1 (en) | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific bispecific binders |
| WO2008124858A2 (en) | 2007-04-11 | 2008-10-23 | F-Star Biotechnologische Forschungs- Und Entwicklungsges. M.B.H. | Targeted receptor |
| CN101802197A (zh) | 2007-05-14 | 2010-08-11 | 比奥根艾迪克Ma公司 | 单链FC（ScFc）区、包含其的结合多肽及与其相关的方法 |
| LT2176298T (lt) | 2007-05-30 | 2018-04-10 | Xencor, Inc. | Būdai ir kompozicijos, skirti cd32b ekspresuojančių ląstelių slopinimui |
| JP6071165B2 (ja) | 2007-05-31 | 2017-02-01 | ゲンマブ エー／エス | 安定なＩｇＧ４抗体 |
| BRPI0812562A2 (pt) | 2007-06-12 | 2019-09-24 | Trubion Pharmaceuticals Inc | composições terapêuticas anti-cd20 e métodos |
| ES2975748T3 (es) | 2007-06-26 | 2024-07-12 | F Star Therapeutics Ltd | Presentación de agentes de unión |
| US8680293B2 (en) | 2007-08-01 | 2014-03-25 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| EP2187971A2 (en) | 2007-08-01 | 2010-05-26 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | A fold-back diabody diphtheria toxin immunotoxin and methods of use |
| JP2010538012A (ja) | 2007-08-28 | 2010-12-09 | バイオジェン アイデック マサチューセッツ インコーポレイテッド | Ｉｇｆ−１ｒの複数のエピトープに結合する組成物 |
| EP2033657A1 (de) | 2007-09-04 | 2009-03-11 | Trion Pharma Gmbh | Intraoperative trifunktionale Antikörper-Applikation zur Prophylaxe intraperitonealer Tumorzelldissemination |
| JP5963341B2 (ja) | 2007-09-14 | 2016-08-10 | アムジエン・インコーポレーテツド | 均質な抗体集団 |
| CN106519025B (zh) | 2007-09-26 | 2021-04-23 | 中外制药株式会社 | 利用cdr的氨基酸取代来改变抗体等电点的方法 |
| CA2700714C (en) | 2007-09-26 | 2018-09-11 | Ucb Pharma S.A. | Dual specificity antibody fusions |
| KR102339457B1 (ko) | 2007-09-26 | 2021-12-14 | 추가이 세이야쿠 가부시키가이샤 | 항체 정상영역 개변체 |
| AR066172A1 (es) * | 2007-09-28 | 2009-07-29 | Chugai Pharmaceutical Co Ltd | Metodo para la preparacion de un anticuerpo antiglipicano 3 con modulada cinetica plasmatica mediante variacion de la semivida plasmatica. |
| KR101616758B1 (ko) * | 2007-12-26 | 2016-04-29 | 젠코어 인코포레이티드 | ＦｃＲｎ에 대한 변경된 결합성을 갖는 Ｆｃ 변이체 |
| ES2563027T3 (es) | 2008-01-07 | 2016-03-10 | Amgen Inc. | Método para fabricación de moléculas heterodímeras Fc de anticuerpos utilizando efectos de conducción electrostática |
| WO2009106096A1 (en) | 2008-02-27 | 2009-09-03 | Fresenius Biotech Gmbh | Treatment of resistant tumors with trifunctional antibodies |
| SG189772A1 (en) | 2008-04-11 | 2013-05-31 | Trubion Pharmaceuticals Inc | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
| PL2282773T3 (pl) | 2008-05-02 | 2014-08-29 | Seattle Genetics Inc | Sposoby i kompozycje do wytwarzania przeciwciał i pochodnych przeciwciał o obniżonej fukozylacji rdzeniowej |
| NZ589434A (en) | 2008-06-03 | 2012-11-30 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
| WO2010028796A1 (en) | 2008-09-10 | 2010-03-18 | F. Hoffmann-La Roche Ag | Trispecific hexavalent antibodies |
| US20170247470A9 (en) | 2008-09-17 | 2017-08-31 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| KR101783272B1 (ko) | 2008-09-17 | 2017-09-29 | 젠코어 인코포레이티드 | ＩｇＥ-매개된 장애를 치료하기 위한 신규 조성물 및 방법 |
| PE20110926A1 (es) | 2008-09-26 | 2011-12-29 | Roche Glycart Ag | Anticuerpos biespecificos anti-egfr/anti-igf-1r |
| ES2582603T5 (es) | 2008-10-01 | 2022-12-02 | Amgen Res Munich Gmbh | Anticuerpos biespecíficos de cadena sencilla con especificidad por antígenos diana de alto peso molecular |
| EP2352765B1 (en) | 2008-10-01 | 2018-01-03 | Amgen Research (Munich) GmbH | Cross-species-specific single domain bispecific single chain antibody |
| US20120034228A1 (en) | 2008-10-01 | 2012-02-09 | Micromet Ag | CROSS-SPECIES-SPECIFIC PSCAxCD3, CD19xCD3, C-METxCD3, ENDOSIALINxCD3, EPCAMxCD3, IGF-1RxCD3 OR FAPALPHAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY |
| WO2010037836A2 (en) | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific psmaxcd3 bispecific single chain antibody |
| CN105218673A (zh) | 2008-10-10 | 2016-01-06 | 新兴产品开发西雅图有限公司 | Tcr复合物免疫治疗剂 |
| HUE035798T2 (en) | 2008-11-03 | 2018-05-28 | Syntarga Bv | CC-1065 analogues and conjugates |
| CN102369291A (zh) | 2009-01-23 | 2012-03-07 | 比奥根艾迪克Ma公司 | 效应子功能降低的稳定Fc多肽及使用方法 |
| AU2010221156A1 (en) | 2009-03-06 | 2011-09-22 | Genentech, Inc. | Antibody formulation |
| EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
| CN102369215B (zh) | 2009-04-02 | 2015-01-21 | 罗切格利卡特公司 | 包含全长抗体和单链Fab片段的多特异性抗体 |
| MX2011010166A (es) | 2009-04-07 | 2011-10-11 | Roche Glycart Ag | Anticuerpos biespecificos anti-erbb-3/anti-c-met. |
| DK2417156T3 (en) | 2009-04-07 | 2015-03-02 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| JP5497887B2 (ja) | 2009-04-07 | 2014-05-21 | ロシュ グリクアート アクチェンゲゼルシャフト | 二重特異性抗ＥｒｂＢ−２／抗ｃ−Ｍｅｔ抗体 |
| EP2241576A1 (en) | 2009-04-17 | 2010-10-20 | Trion Pharma Gmbh | Use of trifunctional bispecific antibodies for the treatment of tumors associated with CD133+/EpCAM+ cancer stem cells |
| CN101531718B (zh) * | 2009-04-22 | 2011-11-02 | 中国人民解放军南京军区军事医学研究所 | 抗VEGFR-2抗体嵌合Fab抗体片段及其制备方法、应用 |
| MX368932B (es) | 2009-06-26 | 2019-10-22 | Regeneron Pharma | Anticuerpos biespecificos facilmente aislados con formato de inmunoglobulina original. |
| EP3205723A1 (en) | 2009-06-26 | 2017-08-16 | i2 Pharmaceuticals, Inc. | Expression of surrogate light chains |
| WO2011005621A1 (en) | 2009-07-08 | 2011-01-13 | Amgen Inc. | Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| DE102009045006A1 (de) | 2009-09-25 | 2011-04-14 | Technische Universität Dresden | Anti-CD33 Antikörper und ihre Anwendung zum Immunotargeting bei der Behandlung von CD33-assoziierten Erkrankungen |
| EP2504360B1 (en) | 2009-11-23 | 2018-08-15 | Amgen Inc. | Monomeric antibody fc |
| EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
| SI2506871T1 (sl) | 2009-11-30 | 2016-12-30 | Janssen Biotech, Inc. | Mutanti Fc protitelesa z odstranjenimi efektorskimi funkcijami |
| KR101856792B1 (ko) | 2009-12-25 | 2018-05-11 | 추가이 세이야쿠 가부시키가이샤 | 폴리펩티드 다량체를 정제하기 위한 폴리펩티드의 개변방법 |
| US20130129723A1 (en) | 2009-12-29 | 2013-05-23 | Emergent Product Development Seattle, Llc | Heterodimer Binding Proteins and Uses Thereof |
| SI2519543T1 (sl) | 2009-12-29 | 2016-08-31 | Emergent Product Development Seattle, Llc | Beljakovine, ki se vežejo s heterodimeri in njihova uporaba |
| JP2013523098A (ja) | 2010-03-29 | 2013-06-17 | ザイムワークス，インコーポレイテッド | 強化又は抑制されたエフェクター機能を有する抗体 |
| US9150663B2 (en) | 2010-04-20 | 2015-10-06 | Genmab A/S | Heterodimeric antibody Fc-containing proteins and methods for production thereof |
| KR101860963B1 (ko) | 2010-04-23 | 2018-05-24 | 제넨테크, 인크. | 이종다량체 단백질의 생산 |
| WO2011143545A1 (en) | 2010-05-14 | 2011-11-17 | Rinat Neuroscience Corporation | Heterodimeric proteins and methods for producing and purifying them |
| EP2580243B1 (en) | 2010-06-09 | 2019-10-16 | Genmab A/S | Antibodies against human cd38 |
| EP3029066B1 (en) | 2010-07-29 | 2019-02-20 | Xencor, Inc. | Antibodies with modified isoelectric points |
| JP5964300B2 (ja) | 2010-08-02 | 2016-08-03 | マクロジェニクス，インコーポレーテッド | 共有結合型ダイアボディおよびその使用 |
| WO2012032080A1 (en) | 2010-09-07 | 2012-03-15 | F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H | Stabilised human fc |
| RU2604490C2 (ru) | 2010-11-05 | 2016-12-10 | Займворкс Инк. | ДИЗАЙН УСТОЙЧИВОГО ГЕТЕРОДИМЕРНОГО АНТИТЕЛА С МУТАЦИЯМИ В Fc ДОМЕНЕ |
| ES2694564T3 (es) | 2011-02-10 | 2018-12-21 | Roche Glycart Ag | Polipéptidos de interleucina-2 mutantes |
| JP6101638B2 (ja) | 2011-03-03 | 2017-03-22 | ザイムワークス，インコーポレイテッド | 多価ヘテロマルチマー足場設計及び構築物 |
| CA2829628A1 (en) | 2011-03-11 | 2012-09-20 | Amgen Inc. | Method of correlated mutational analysis to improve therapeutic antibodies |
| JP5972915B2 (ja) | 2011-03-16 | 2016-08-17 | アムジエン・インコーポレーテツド | Ｆｃ変異体 |
| EA201791693A1 (ru) | 2011-03-25 | 2018-05-31 | Гленмарк Фармасьютикалс С.А. | Гетеродимерные иммуноглобулины |
| TWI838039B (zh) | 2011-03-28 | 2024-04-01 | 法商賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
| HUE041335T2 (hu) | 2011-03-29 | 2019-05-28 | Roche Glycart Ag | Antitest FC-variánsok |
| EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
| SG195072A1 (en) | 2011-05-21 | 2013-12-30 | Macrogenics Inc | Cd3-binding molecules capable of binding to human and non-human cd3 |
| WO2012162277A1 (en) | 2011-05-25 | 2012-11-29 | Merck Sharp & Dohme Corp. | METHOD FOR PREPARING Fc-CONTAINING POLYPEPTIDES HAVING IMPROVED PROPERTIES |
| US20140155581A1 (en) | 2011-07-06 | 2014-06-05 | Medimmune, Llc | Methods For Making Multimeric Polypeptides |
| WO2013016714A1 (en) | 2011-07-28 | 2013-01-31 | Sea Lane Biotechnologies | Sur-binding proteins against erbb3 |
| WO2013022855A1 (en) | 2011-08-05 | 2013-02-14 | Xencor, Inc. | Antibodies with modified isoelectric points and immunofiltering |
| ES2857734T3 (es) | 2011-08-23 | 2021-09-29 | Roche Glycart Ag | Moléculas de unión a antígeno activadoras de linfocitos T biespecíficas |
| CA2843158A1 (en) | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| CA3182462A1 (en) | 2011-10-10 | 2013-04-18 | Xencor, Inc. | A method for purifying antibodies |
| US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| ES2687245T3 (es) | 2011-10-20 | 2018-10-24 | Esbatech - A Novartis Company Llc | Anticuerpo estable de unión a antígenos múltiples |
| WO2013065708A1 (ja) | 2011-10-31 | 2013-05-10 | 中外製薬株式会社 | 重鎖と軽鎖の会合が制御された抗原結合分子 |
| EP2773671B1 (en) | 2011-11-04 | 2021-09-15 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| US9975956B2 (en) | 2011-12-22 | 2018-05-22 | I2 Pharmaceuticals, Inc. | Surrogate binding proteins which bind DR4 and/or DR5 |
| CA2865158C (en) | 2012-02-24 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for promoting disappearance of antigen via fc.gamma.riib |
| CN120383672A (zh) | 2012-04-20 | 2025-07-29 | 美勒斯公司 | 用于产生免疫球蛋白样分子的方法和手段 |
| EP2857419B1 (en) | 2012-05-30 | 2021-01-13 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for eliminating aggregated antigens |
| WO2014004586A1 (en) | 2012-06-25 | 2014-01-03 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
| EP2872170A4 (en) | 2012-07-13 | 2016-06-22 | Zymeworks Inc | ASYMMETRIC BISPECIFIC HETERODIMERS WITH ANTI-CD3 CONSTRUCTS |
| WO2014018572A2 (en) | 2012-07-23 | 2014-01-30 | Zymeworks Inc. | Immunoglobulin constructs comprising selective pairing of the light and heavy chains |
| CN120365432A (zh) | 2012-11-21 | 2025-07-25 | 武汉友芝友生物制药股份有限公司 | 双特异性抗体 |
| US20140377269A1 (en) | 2012-12-19 | 2014-12-25 | Adimab, Llc | Multivalent antibody analogs, and methods of their preparation and use |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| WO2014113510A1 (en) | 2013-01-15 | 2014-07-24 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| WO2014164553A1 (en) | 2013-03-13 | 2014-10-09 | Imaginab, Inc. | Antigen binding constructs to cd8 |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| JP6594855B2 (ja) | 2013-03-15 | 2019-10-23 | ゼンコア インコーポレイテッド | ヘテロ二量体タンパク質 |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| EP3421495A3 (en) | 2013-03-15 | 2019-05-15 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
| JP2016538275A (ja) | 2013-11-04 | 2016-12-08 | グレンマーク ファーマシューティカルズ， エセ．アー． | Ｔ細胞再標的化ヘテロ二量体免疫グロブリン（ｈｅｔｅｒｏ−ｄｉｍｅｒｉｃ ｉｍｍｕｎｏｇｌｏｂｕｌｉｎ）の製造 |
| MX385936B (es) | 2014-03-28 | 2025-03-11 | Xencor Inc | Anticuerpos biespecíficos que se unen a cd38 y cd3. |
| EP3194449A1 (en) | 2014-07-24 | 2017-07-26 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| US20160176969A1 (en) | 2014-11-26 | 2016-06-23 | Xencor, Inc. | Heterodimeric antibodies including binding to cd8 |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| HRP20211273T1 (hr) | 2014-11-26 | 2021-11-12 | Xencor, Inc. | Heterodimerna protutijela koja vežu cd3 i cd20 |
| EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
| US11392902B2 (en) | 2017-06-06 | 2022-07-19 | United Parcel Service Of America, Inc. | Systems, methods, apparatuses and computer program products for providing notification of items for pickup and delivery |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12084513B2 (en) | 2017-11-14 | 2024-09-10 | Chugai Seiyaku Kabushiki Kaisha | Anti-C1S antibodies and methods of use |
| US12473353B2 (en) | 2019-05-15 | 2025-11-18 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule, a pharmaceutical composition, and a method |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012016227A3 (en) | 2012-05-03 |
| CN103052649B (zh) | 2015-12-16 |
| CA2806252A1 (en) | 2012-02-02 |
| US20170174757A1 (en) | 2017-06-22 |
| AU2017204797A1 (en) | 2017-07-27 |
| US20120028304A1 (en) | 2012-02-02 |
| US20140249297A1 (en) | 2014-09-04 |
| DK3029066T3 (da) | 2019-05-20 |
| CN105585630A (zh) | 2016-05-18 |
| JP2013539361A (ja) | 2013-10-24 |
| AU2011283694B2 (en) | 2017-04-13 |
| CN103052649A (zh) | 2013-04-17 |
| AU2011283694A1 (en) | 2013-02-28 |
| EP3029066A3 (en) | 2016-09-14 |
| US8637641B2 (en) | 2014-01-28 |
| AU2017204797B2 (en) | 2019-11-21 |
| US9605061B2 (en) | 2017-03-28 |
| WO2012016227A2 (en) | 2012-02-02 |
| CA2806252C (en) | 2019-05-14 |
| EP3029066A2 (en) | 2016-06-08 |
| CN105585630B (zh) | 2020-09-15 |
| IL224441B (en) | 2021-12-01 |
| EP3029066B1 (en) | 2019-02-20 |
| EP2598530A2 (en) | 2013-06-05 |
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