CA3141690A1 - Engineering the hinge region to drive antibody dimerization - Google Patents
Engineering the hinge region to drive antibody dimerizationInfo
- Publication number
- CA3141690A1 CA3141690A1 CA3141690A CA3141690A CA3141690A1 CA 3141690 A1 CA3141690 A1 CA 3141690A1 CA 3141690 A CA3141690 A CA 3141690A CA 3141690 A CA3141690 A CA 3141690A CA 3141690 A1 CA3141690 A1 CA 3141690A1
- Authority
- CA
- Canada
- Prior art keywords
- amino acid
- region
- domain
- antibody
- heavy chain
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
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Classifications
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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
- A61K39/39591—Stabilisation, fragmentation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962854907P | 2019-05-30 | 2019-05-30 | |
| US62/854,907 | 2019-05-30 | ||
| PCT/US2020/035196 WO2020243477A2 (en) | 2019-05-30 | 2020-05-29 | Engineering the hinge region to drive antibody dimerization |
Publications (1)
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|---|---|
| CA3141690A1 true CA3141690A1 (en) | 2020-12-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3141690A Pending CA3141690A1 (en) | 2019-05-30 | 2020-05-29 | Engineering the hinge region to drive antibody dimerization |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20220235148A1 (enExample) |
| EP (1) | EP3976643A2 (enExample) |
| JP (2) | JP7500619B2 (enExample) |
| KR (1) | KR20220016139A (enExample) |
| CN (2) | CN119431599A (enExample) |
| AU (1) | AU2020283890A1 (enExample) |
| CA (1) | CA3141690A1 (enExample) |
| EA (1) | EA202193322A1 (enExample) |
| MX (1) | MX2021014534A (enExample) |
| SG (1) | SG11202112926YA (enExample) |
| TW (2) | TWI879770B (enExample) |
| WO (1) | WO2020243477A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110669137B (zh) * | 2019-10-24 | 2021-07-16 | 高新 | 一种多特异性抗体及其制备方法和用途 |
| AU2022261269A1 (en) * | 2021-04-23 | 2023-11-09 | Chimagen Biosciences, Ltd | Heterodimeric antibodies and antigen-binding fragment thereof |
| JP2025524024A (ja) * | 2022-07-22 | 2025-07-25 | イノベント バイオロジクス（スーチョウ）カンパニー，リミティド | 多重特異性抗体の重鎖及び軽鎖の相同対合を促進する変異体 |
| CN115232214A (zh) * | 2022-08-16 | 2022-10-25 | 广州市拜沃思生物科技有限公司 | 一种双特异性抗体及其制备方法和应用 |
| TW202506725A (zh) * | 2023-04-07 | 2025-02-16 | 美商麥迪紐有限責任公司 | 三特異性工程化抗體 |
| WO2024242490A1 (ko) * | 2023-05-24 | 2024-11-28 | 삼성바이오로직스 주식회사 | Ch3 도메인 변이체 또는 이를 포함하는 이중 특이적 항체 |
| WO2025167974A1 (zh) * | 2024-02-07 | 2025-08-14 | 上海齐鲁制药研究中心有限公司 | 多特异性抗体或抗原结合片段 |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US30985A (en) | 1860-12-18 | Thomas l | ||
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| US4965195A (en) | 1987-10-26 | 1990-10-23 | Immunex Corp. | Interleukin-7 |
| US4968607A (en) | 1987-11-25 | 1990-11-06 | Immunex Corporation | Interleukin-1 receptors |
| EP0435911B1 (en) | 1988-09-23 | 1996-03-13 | Cetus Oncology Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| AU643427B2 (en) | 1988-10-31 | 1993-11-18 | Immunex Corporation | Interleukin-4 receptors |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| ATE356869T1 (de) | 1990-01-12 | 2007-04-15 | Amgen Fremont Inc | Bildung von xenogenen antikörpern |
| US6713610B1 (en) | 1990-01-12 | 2004-03-30 | Raju Kucherlapati | Human antibodies derived from immunized xenomice |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| AU651596B2 (en) | 1990-06-05 | 1994-07-28 | Immunex Corporation | Type II interleukin-1 receptors |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| CA2089661C (en) | 1990-08-29 | 2007-04-03 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| CA2111348A1 (en) | 1991-06-14 | 1992-12-23 | John S. Logan | Production of human hemoglobin in transgenic pigs |
| JPH06508880A (ja) | 1991-07-08 | 1994-10-06 | ユニバーシティ オブ マサチューセッツ アット アムハースト | サーモトロピック液晶セグメント化ブロックコポリマー |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| SG48760A1 (en) | 1992-07-24 | 2003-03-18 | Abgenix Inc | Generation of xenogenetic antibodies |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
| AU728657B2 (en) | 1996-03-18 | 2001-01-18 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6165476A (en) * | 1997-07-10 | 2000-12-26 | Beth Israel Deaconess Medical Center | Fusion proteins with an immunoglobulin hinge region linker |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| US7371849B2 (en) | 2001-09-13 | 2008-05-13 | Institute For Antibodies Co., Ltd. | Methods of constructing camel antibody libraries |
| JP2008511337A (ja) | 2004-09-02 | 2008-04-17 | ジェネンテック・インコーポレーテッド | ヘテロ多量体分子 |
| KR101516823B1 (ko) | 2006-03-17 | 2015-05-07 | 바이오겐 아이덱 엠에이 인코포레이티드 | 안정화된 폴리펩티드 조성물 |
| EP3202786A3 (en) | 2007-03-12 | 2017-10-11 | ESBATech, an Alcon Biomedical Research Unit LLC | Sequence based engineering and optimization of single chain antibodies |
| CA2681974C (en) | 2007-03-29 | 2019-12-31 | Genmab A/S | Bispecific antibodies and methods for production thereof |
| US8793074B2 (en) | 2007-06-21 | 2014-07-29 | Saint Louis University | Sequence covariance networks, methods and uses therefor |
| CA2689941C (en) | 2007-06-25 | 2019-10-29 | Esbatech Ag | Methods of modifying antibodies, and modified antibodies with improved functional properties |
| CA2756244A1 (en) * | 2009-04-02 | 2010-10-07 | Roche Glycart Ag | Multispecific antibodies comprising full length antibodies and single chain fab fragments |
| PL2560993T3 (pl) | 2010-04-20 | 2024-11-04 | Genmab A/S | Heterodimeryczne białka zawierające region FC przeciwciała i sposoby ich wytwarzania |
| US9527926B2 (en) * | 2010-05-14 | 2016-12-27 | Rinat Neuroscience Corp. | Heterodimeric proteins and methods for producing and purifying them |
| NZ604003A (en) | 2010-05-27 | 2015-04-24 | Genmab As | Monoclonal antibodies against her2 |
| TWI687441B (zh) * | 2011-06-30 | 2020-03-11 | 中外製藥股份有限公司 | 異源二聚化多胜肽 |
| SG10201805291TA (en) | 2011-10-27 | 2018-08-30 | Genmab As | Production of heterodimeric proteins |
| EP2794653B1 (en) * | 2011-12-23 | 2019-03-13 | Pfizer Inc | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
| DK3004174T3 (da) * | 2013-05-31 | 2019-07-22 | Zymeworks Inc | Heteromultimerer med reduceret eller nedreguleret effektorfunktion |
| WO2015017710A1 (en) * | 2013-07-31 | 2015-02-05 | Amgen Inc. | Growth differentiation factor 15 (gdf-15) constructs |
| US10392438B2 (en) * | 2014-05-16 | 2019-08-27 | Pfizer Inc. | Bispecific antibodies |
| WO2018030806A1 (ko) * | 2016-08-10 | 2018-02-15 | 아주대학교산학협력단 | 항체 중쇄불변부위 이종이중체에 융합된 사이토카인 및 이를 포함하는 약제학적 조성물 |
-
2020
- 2020-05-29 SG SG11202112926YA patent/SG11202112926YA/en unknown
- 2020-05-29 CN CN202411591082.1A patent/CN119431599A/zh active Pending
- 2020-05-29 CN CN202080054199.XA patent/CN114174344B/zh active Active
- 2020-05-29 MX MX2021014534A patent/MX2021014534A/es unknown
- 2020-05-29 EA EA202193322A patent/EA202193322A1/ru unknown
- 2020-05-29 TW TW109118067A patent/TWI879770B/zh active
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- 2020-05-29 TW TW114109900A patent/TW202525844A/zh unknown
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- 2020-05-29 EP EP20761358.9A patent/EP3976643A2/en active Pending
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- 2024-06-04 JP JP2024090480A patent/JP2024113040A/ja active Pending
Also Published As
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|---|---|
| TWI879770B (zh) | 2025-04-11 |
| TW202525844A (zh) | 2025-07-01 |
| WO2020243477A3 (en) | 2021-01-07 |
| JP2022534901A (ja) | 2022-08-04 |
| US20220235148A1 (en) | 2022-07-28 |
| WO2020243477A2 (en) | 2020-12-03 |
| CN114174344A (zh) | 2022-03-11 |
| AU2020283890A1 (en) | 2021-12-16 |
| EP3976643A2 (en) | 2022-04-06 |
| MX2021014534A (es) | 2022-02-11 |
| JP7500619B2 (ja) | 2024-06-17 |
| KR20220016139A (ko) | 2022-02-08 |
| JP2024113040A (ja) | 2024-08-21 |
| CN119431599A (zh) | 2025-02-14 |
| EA202193322A1 (ru) | 2022-03-10 |
| TW202110877A (zh) | 2021-03-16 |
| CN114174344B (zh) | 2024-11-22 |
| SG11202112926YA (en) | 2021-12-30 |
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