RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties
Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development crite...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2330113 |
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| author | Barnabas Nyesiga Mattias Levin Anna Säll Anna Rosén Kim Jansson Sara Fritzell Karin Hägerbrand Dietmar Weilguny Laura von Schantz |
| author_facet | Barnabas Nyesiga Mattias Levin Anna Säll Anna Rosén Kim Jansson Sara Fritzell Karin Hägerbrand Dietmar Weilguny Laura von Schantz |
| author_sort | Barnabas Nyesiga |
| collection | DOAJ |
| description | Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development criteria. The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes. Our data demonstrate that RUBY bsAbs are compatible with small-scale production systems for screening purposes and can be produced at high yields (>3 g/L) from stable cell lines. The bsAbs produced are shown to, in general, contain low amounts of aggregates and display favorable solubility and stress endurance profiles. Further, compatibility with various IgG isotypes is shown and tailored Fc gamma receptor binding confirmed. Also, retained interaction with FcRn is demonstrated to translate into a pharmacokinetic profile in mice and non-human primates that is comparable to mAb controls. Functionality of conditional active RUBY bsAbs is confirmed in vitro. Anti-tumor effects in vivo have previously been demonstrated, and shown to be superior to a comparable mAb, and here it is further shown that RUBY bsAbs penetrate and localize to tumor tissue in vivo. In all, the RUBY format has attractive mAb-like attributes and offers the possibility to mitigate many of the development challenges linked to other bsAb formats, facilitating both high functionality and developability. |
| format | Article |
| id | doaj-art-3554ed116f6c45079b118217d1d8fd6f |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-3554ed116f6c45079b118217d1d8fd6f2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2330113RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability propertiesBarnabas Nyesiga0Mattias Levin1Anna Säll2Anna Rosén3Kim Jansson4Sara Fritzell5Karin Hägerbrand6Dietmar Weilguny7Laura von Schantz8Alligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenAlligator Bioscience AB, Medicon Village, Lund, SwedenDespite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development criteria. The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes. Our data demonstrate that RUBY bsAbs are compatible with small-scale production systems for screening purposes and can be produced at high yields (>3 g/L) from stable cell lines. The bsAbs produced are shown to, in general, contain low amounts of aggregates and display favorable solubility and stress endurance profiles. Further, compatibility with various IgG isotypes is shown and tailored Fc gamma receptor binding confirmed. Also, retained interaction with FcRn is demonstrated to translate into a pharmacokinetic profile in mice and non-human primates that is comparable to mAb controls. Functionality of conditional active RUBY bsAbs is confirmed in vitro. Anti-tumor effects in vivo have previously been demonstrated, and shown to be superior to a comparable mAb, and here it is further shown that RUBY bsAbs penetrate and localize to tumor tissue in vivo. In all, the RUBY format has attractive mAb-like attributes and offers the possibility to mitigate many of the development challenges linked to other bsAb formats, facilitating both high functionality and developability.https://www.tandfonline.com/doi/10.1080/19420862.2024.2330113Antibody formatbispecific antibodiesIgGimmuno-oncologyRUBY®tetravalent |
| spellingShingle | Barnabas Nyesiga Mattias Levin Anna Säll Anna Rosén Kim Jansson Sara Fritzell Karin Hägerbrand Dietmar Weilguny Laura von Schantz RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties mAbs Antibody format bispecific antibodies IgG immuno-oncology RUBY® tetravalent |
| title | RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| title_full | RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| title_fullStr | RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| title_full_unstemmed | RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| title_short | RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties |
| title_sort | ruby r a tetravalent 2 2 bispecific antibody format with excellent functionality and igg like stability pharmacology and developability properties |
| topic | Antibody format bispecific antibodies IgG immuno-oncology RUBY® tetravalent |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2330113 |
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