Antibodies comprising a common light chain and uses thereof
Inventors
Charpentier, Thomas • Chambers, Ross • Stafford, Lewis J. • Barnes, Trevor • Sullivan, Jonathan T.
Assignees
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Publication Number
US-11254736-B2
Publication Date
2022-02-22
Expiration Date
Abstract
Peptides and uses thereof, such as a common light chain in an antibody, are provided.
Core Innovation
The invention relates to an antibody light chain variable region defined by selected light chain CDR sequences, specifically light chain CDR1 (LCDR1), CDR2 (LCDR2), and CDR3 (LCDR3), where each LCDR is assigned to one of multiple SEQ ID -defined peptide options. The disclosed combinations constrain LCDR1, LCDR2, and LCDR3 to particular SEQ ID numbers, and multiple selectable LCDR1/LCDR2/LCDR3 sets are presented within the same technical framework. These combinations are described as forming an antibody light chain variable region.
The framework context defines the antibody light chain variable region as including framework regions using specified framework peptide SEQ IDs and as framed by framework regions and the LCDR peptides in a defined ordering within a VL domain. This establishes a constrained VL architecture based on specific SEQ ID -defined CDR and framework components. The common light-chain concept is used so that multiple antibody formats can share a common light chain variable region while presenting defined CDR content.
The disclosure further frames the defined light chain variable regions in terms of binding specificity or affinity to an epitope and the resulting functional uses. The common light-chain concept enables pairing with various heavy-chain VH domains to bind multiple targets, and the document describes antibody forms such as full IgG and antibody fragments, including scFv, Fab, and F(ab2). In the partial content provided, the targets include PD-1, PD-L1, PD-L2, CTLA4, and tetraspanins such as CD151, IGSF8, CD315, CD147, CD59, CD81, and CD63.
Claims Coverage
The provided independent claim coverage centers on an antibody light chain variable region defined by selectable, SEQ ID specified LCDR1/LCDR2/LCDR3 combinations. Dependent claims further narrow the claim scope by adding sequence-identity constraints anchored to full-length light chain variable region SEQ IDs and by specifying additional nucleic-acid and cellular embodiments.
Specific LCDR1/LCDR2/LCDR3 combination defined by SEQ ID NOs
An antibody light chain variable region comprising a light chain CDR1 (LCDR1), a light chain CDR2 (LCDR2), and a light chain CDR3 (LCDR3), wherein the light chain variable region comprises a LCDR1 of SEQ ID NO: 19; a LCDR2 of SEQ ID NO: 21; and a LCDR3 of SEQ ID NO: 23; or a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 60; and a LCDR3 of SEQ ID NO: 61; or a LCDR1 of SEQ ID NO: 63; a LCDR2 of SEQ ID NO: 64; and a LCDR3 of SEQ ID NO: 65; or a LCDR1 of SEQ ID NO: 66; a LCDR2 of SEQ ID NO: 67; and a LCDR3 of SEQ ID NO: 68; or a LCDR1 of SEQ ID NO: 84; a LCDR2 of SEQ ID NO: 64; and a LCDR3 of SEQ ID NO: 73; or a LCDR1 of SEQ ID NO: 49; a LCDR2 of SEQ ID NO: 77; and a LCDR3 of SEQ ID NO: 78; or a LCDR1 of SEQ ID NO: 57; a LCDR2 of SEQ ID NO: 79; and a LCDR3 of SEQ ID NO: 80.
Sequence identity refinement to an anchored full-length sequence
The antibody light chain variable region amino acid sequence has at least 90% identity to SEQ ID NO: 3 and includes CDR1/2/3 sequences of SEQ ID NO: 52/54/56, respectively.
Tighter sequence identity refinement with fixed CDR sequences
The antibody light chain variable region contains amino acid sequences with at least 95% identity to SEQ ID NO: 3 and specifies CDR1/2/3 sequences as SEQ ID NOs: 52/54/56, respectively.
Full-length sequence inclusion
The antibody light chain variable region includes the amino acid sequence of SEQ ID NO: 3.
Cell comprising nucleic acid encoding the light chain variable region
A cell is claimed that comprises the nucleic acid molecule of claim 20.
Selectable LCDR1/LCDR2/LCDR3 combination-defined light chain variable region
An antibody light chain variable region comprising a light chain CDR1 (LCDR1), a light chain CDR2 (LCDR2), and a light chain CDR3 (LCDR3), wherein the light chain variable region comprises specified LCDR1, LCDR2, and LCDR3 peptides selected from multiple SEQ ID NO combinations.
Identity-threshold narrowing of light chain variable region
An antibody light chain variable region where the amino acid sequence has at least 90% identity or at least 95% identity to a specified full-length light chain variable region SEQ ID, while the CDR1, CDR2, and CDR3 sequences are specified as fixed SEQ ID NOs.
Exact full-length light chain variable region sequence inclusion
An antibody light chain variable region that includes the amino acid sequence of a specified light chain variable region SEQ ID NO.
Specific LCDR1/LCDR2/LCDR3 set selection
An antibody light chain variable region that defines the LCDR1, LCDR2, and LCDR3 sequences corresponding to particular SEQ ID NOs selected from the sets presented in the independent claim.
Encoding nucleic acid and cell comprising the light chain variable region
A nucleic acid molecule encoding the specified antibody light chain variable region, and a cell comprising the nucleic acid molecule encoding the antibody light chain variable region.
Overall, the claim coverage is centered on an antibody light chain variable region defined by SEQ ID specified LCDR1/LCDR2/LCDR3 combinations. The dependent claims narrow the scope through identity thresholds, exact full-length sequence inclusion, selection of particular LCDR1/2/3 sets, and further embodiments covering nucleic acids and cells containing the encoding molecules.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Detection of a target protein in biological samples using antibodies with the common light chain.
Therapeutic or targeting roles, including multi-specific therapeutic formats.
ADCC/ADC/CAR-T/CD3 binding molecule contexts, as part of the therapeutic or targeting concepts described.
The targets include PD-1, PD-L1, PD-L2, CTLA4, and tetraspanins such as CD151, IGSF8, CD315, CD147, CD59, CD81, and CD63.
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