CD3 binding antibodies
Inventors
Trinklein, Nathan • van Schooten, Wim • Aldred, Shelley Force • Harris, Katherine • Pham, Duy
Assignees
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Publication Number
US-11505606-B2
Publication Date
2022-11-22
Expiration Date
Abstract
The present invention relates to human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.
Core Innovation
The invention relates to a family of human anti-CD3 antigen-binding polypeptides and multispecific/bispecific antibodies that activate CD3+ T cells. A first binding moiety is configured to bind human CD3δ via defined heavy-chain variable domain and light-chain variable domain CDR1/CDR2/CDR3 sequences, including specified sequence identities and SEQ ID numbers.
The antibodies further comprise a second binding moiety with binding specificity for a tumor-associated antigen (TMA) or a tumor-specific antigen (TSA). By combining anti-CD3 binding with targeting of a tumor antigen such as BCMA, including aBCMA, the disclosed formats produce tumor-associated and tumor-specific functional outcomes while tuning binding affinity and cytokine release to reduce toxicity, including cytokine release syndrome.
The disclosure includes described functional outcomes and correlations, including IL-2, IFN-γ, IL-6, IL-10, and TNF-α cytokine release and correlations between bispecific anti-CD3:aBCMA tumor cell lysis and cytokine release and binding affinity. The document also outlines related antibody and protein formats, including scFv, tandem/scFv, heavy-chain-only antibodies, and TCA, and general composition and use concepts across cancers and infections.
Claims Coverage
The document includes one independent claim defining a multispecific antibody with a first binding moiety specific for human CD3δ using specified heavy- and light-chain variable domain CDR sequences, and a second binding moiety specific for a tumor-associated antigen (TM) or a tumor-specific antigen (TSA). Inventive features are centered on the CD3δ-binding CDR sequence combinations and the paired TM/TSA-binding moiety.
CD3δ-specific first binding moiety with defined heavy- and light-chain CDR sequences
A heavy chain variable domain comprising a CDR1 sequence comprising GFTFDDYA (SEQ ID NO: 29) and/or a CDR1 sequence comprising GFTFHNYA (SEQ ID NO: 34), a CDR2 sequence comprising ISWNSGSI (SEQ ID NO: 24), and a CDR3 sequence comprising AKDSRGYGDYRLGGAY (SEQ ID NO: 41) or AKDSRGYGDYSLGGAY (SEQ ID NO: 43); together with a light chain variable domain comprising a CDR1 sequence comprising QSVSSN (SEQ ID NO: 35), a CDR2 sequence comprising GAS (SEQ ID NO: 38), and a CDR3 sequence comprising QQYNNWPWT (SEQ ID NO: 45).
Second binding moiety for a tumor-associated antigen (TM) or tumor-specific antigen (TSA)
A second binding moiety that has binding specificity for a tumor-associated antigen (TM) or a tumor-specific antigen (TSA), paired with the CD3δ-specific first binding moiety to form the multispecific antibody.
Across the independent claim, the core claim coverage is the multispecific antibody architecture that fixes the human CD3δ-binding moiety to specified heavy- and light-chain variable domain CDR sequence sets, with defined SEQ ID numbers, and couples it to a second binding moiety that binds a tumor-associated antigen (TM) or tumor-specific antigen (TSA).
Stated Advantages
Tuning binding affinity and cytokine release to reduce toxicity, including cytokine release syndrome.
Documented Applications
Therapeutic uses and diagnostic uses across cancers and infections, as described for the multispecific and antibody formats.
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