Human antibodies binding to ROR2
Inventors
Grawunder, Ulf • Beerli, Roger • HELLMANN, Ina • Waldmeier, Lorenz
Assignees
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Publication Number
US-11447546-B2
Publication Date
2022-09-20
Expiration Date
Abstract
The present invention relates to fully human antibodies and conjugates thereof, which specifically bind to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2).
Core Innovation
The disclosed invention provides a fully human antibody, or antigen-binding fragment thereof, that specifically binds to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2), including human ROR2 (hROR2). The antibody is defined in terms of heavy chain and light chain CDR sets and their corresponding SEQ ID NOs, with light chain CDR 2 having defined sequences such as KAS, AAS, or LGS.
The disclosure also specifies Ig heavy chain variable region and Ig light chain variable region combinations associated with named antibodies. The antibodies are described as cross-reactive for mouse ROR2 and cynomolgus ROR2, and the platform includes discussion of binding properties and epitope competition.
The disclosure extends to downstream antibody formats, including bi-/multispecific effector-binding antibodies, CAR constructs, antibody drug conjugates (ADC) and antibody effector conjugates (AEC), including sortase site-specific conjugation to toxin/labels. The document also describes detection/diagnostic methods for altered ROR2 levels using labeled anti-ROR2 antibodies, including immunoassays and imaging modalities for tumor screening and monitoring.
Claims Coverage
The provided record includes three independent claim themes. Across these independent claims, the main inventive focus is on fully human ROR2 extracellular-domain binding antibodies defined by specific CDR sets and/or specific Ig variable-region SEQ ID pairs, with additional coverage for ROR2-targeting bi-/multispecific formats and in vitro killing or growth inhibition applications.
Extracellular-domain binding fully human antibody with defined CDR sets
A fully human antibody, or antigen-binding fragment thereof, which specifically binds to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2) and comprises one of the specified CDR sets, including specified heavy chain CDRs 1-3 and light chain CDRs 1 and 3 as set forth in respective SEQ ID NOs, with light chain CDR 2 having the sequence KAS or AAS or LGS.
Extracellular-domain binding fully human antibody with defined Ig variable-region sequence pairs
A fully human antibody, or antigen-binding fragment thereof, which specifically binds to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2), wherein said antibody comprises an Ig heavy chain variable region sequence and an Ig light chain variable region sequence provided as multiple alternative SEQ ID NO heavy/light pairs.
Bi- or multispecific anti-ROR2 first binding domain with an effector-antigen second binding domain
A bi- or multispecific molecule that includes an antibody-based first antigen-binding domain binding to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2) and at least a second antigen-binding domain binding to an effector antigen among CD3, CD16, NKG2D, NKp46, CD2, CD28 and/or CD25.
In vitro killing or growth inhibition of ROR2-expressing cells by administering the anti-ROR2 antibody
A method for killing or inhibiting the growth of an in vitro cell expressing ROR2 by administering a pharmaceutically effective amount or dose of an antibody or an antigen-binding fragment thereof.
The independent claims define fully human antibodies that bind the ROR2 extracellular domain, either by specified CDR combinations or by Ig heavy/light variable-region sequence pairs, and extend to bi-/multispecific effector-binding formats and in vitro killing or growth inhibition of ROR2-expressing cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Detection/diagnostic applications for ROR2 are described, including ELISA, FACS, IHC, Western blotting, and imaging/contrast agent modalities for tumor screening and monitoring.
Therapeutic applications for ROR2-expressing cancers are described, including bi-/multispecific effector-binding antibodies, CAR constructs, antibody drug conjugates (ADC) and antibody effector conjugates (AEC).
In vitro killing or inhibiting growth of an in vitro cell expressing ROR2 by administering an anti-ROR2 antibody or antigen-binding fragment thereof.
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