Anti-transferrin receptor antibodies and uses thereof
AssigneeBiogen MA Inc.
InventorsThomas Owen Cameron, Karl John Mortley Hanf, Benjamin Andrew Smith, Joseph Walter Arndt, Caitlin Bryanna Meeks, Isin Dalkilic-Liddle, Andreas Lehmann, Mark Christopher Julian
Life of this patent
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Abstract
The present disclosure provides anti-transferrin receptor antibodies, compositions comprising the same and methods of use for delivery of cargo to brain tissue. This disclosure also provides polynucleotides and vectors encoding the anti-transferrin receptor antibodies and cells comprising the same, methods of making the antibodies, and molecules comprising the antibodies.
Claims52
An antibody that binds to human transferrin receptor, comprising a heavy chain variable region (VH) comprising VH complementarity determining region (CDR) 1, VH CDR2, and VH CDR3, and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3,
- wherein (a) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 contain collectively one to ten amino acid differences as compared to a parental antibody whose heavy chain CDRs 1, 2, and 3 comprise the amino acid sequences GIDFSSSGYMC (SEQ ID NO:
- XX), CIYTYSSNTYYAASVKG (SEQ ID NO:XX), and GTYGYTGYTYTMGYFSL (SEQ ID NO:
- XX), and whose light chain CDRs 1, 2, and 3 comprise the amino acid sequences QASQNINSYLA (SEQ ID NO:XX), RASSLES (SEQ ID NO:XX), and QSYYYSGSSNYNA (SEQ ID NO:XX), or (b) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 contain collectively one to ten amino acid differences as compared to a parental antibody whose heavy chain CDRs 1, 2, and 3 comprise the amino acid sequences GIDFSSSG (SEQ ID NO:
- XX), TYSS (SEQ ID NO:XX), and TYGYTGYTYTMGYFS (SEQ ID NO:XX), and whose light chain CDRs 1, 2, and 3 comprise the amino acid sequences SQNINSY (SEQ ID NO:XX), RAS (SEQ ID NO:XX), and YYYSGSSNYN (SEQ ID NO:XX), and
- wherein the one to ten amino acid differences as compared to the parental antibody are (using AHo numbering) selected from the group consisting of:
- VH-S32A, VH-S32D, or VH-S32H;
- VH-S33A or VH-S33D;
- VH-S33E or VH-S33H;
- VH-S38A, VH-S38D, or VH-S38H;
- VH-Y59A, VH-Y59D, VH-Y59H, VH-Y59E, or VH-Y59F;
- VH-Y61A, VH-Y61D, or VH-Y61H;
- VH-N67A, VH-N67D, VH-N67E, VH-N67H, VH-N67K, or VH-N67R;
- VH-Y69A, VH-Y69D, VH-Y69E, or VH-Y69H;
- VH-Y113A, VH-Y113D, or VH-Y113H;
- VH-Y116A, VH-Y116D, or VH-Y116H;
- VH-T130A, VH-T130D, or VH-T130H;
- VH-Y131A, VH-Y131D, or VH-Y131H;
- VL-N30S;
- VL-N32S;
- VL-R58D;
- VL-Y111D, VL-Y111H, or VL-Y111S;
- VL-S133A, VL-S133D, or VL-S133H;
- VH-Y61D and VH-N67E;
- VH-N67E and VH-Y69E;
- and
- VL-N30S and VL-N32S.
The antibody of any one of the preceding claims, wherein:
- (i) the VH is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to any one of SEQ ID NOs:
- 100-160;
- and
- (ii) the VL is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to any one of SEQ ID NOs:
- 200-216.
The antibody of any one of the preceding claims, wherein the antibody is (a) monovalent and has a monovalent affinity (KD) for hTfR1 of >10 nM or is bivalent and has a monovalent affinity (KD) for hTfR1 of >100 nM and/or (b) has an off rate (kd) of >=0.01/s.
The antibody of any one of the preceding claims, wherein:
- (i) the HC comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence as set forth in any one of HC-1043 to HC-1094 (as shown in Table 10) and HC-2002 to HC-2020 (as shown in Table 22);
- and
- (ii) the LC comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence as set forth in any one of LC-1095 to LC-1114 (as shown in Table 10) and LC-2021 (as shown in Table 22).
Dependencies are inferred from the claim text.