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US 12,637,522 B2Granted
Monoclonal antibodies against BCMA
AssigneeBristol-Myers Squibb Company
InventorsMinh Diem Vu, Klaus Strein, Oliver Ast, Marina Bacac, Camille Delon, Lydia Jasmin Hanisch, Anne Freimoser-Grundschober, Christian Klein, Ekkehard Moessner, Samuel Moser, Pablo Umana, Tina Weinzierl
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Abstract
The invention relates to new antibodies against BCMA, their manufacture and use.
Claims33
A bispecific antibody, comprising:
- (i) a first BCMA-Fab and a second BCMA-Fab, wherein each of the first and second BCMA-Fabs comprises a variable heavy chain (VH) region comprising a CDR1H region comprising the amino acid sequence of SEQ ID NO:
- 21, a CDR2H region comprising the amino acid sequence of SEQ ID NO:
- 22, and a CDR3H region comprising the amino acid sequence of SEQ ID NO:
- 17;
- and a variable light chain (VL) region comprising a CDR1L region comprising the amino acid sequence of SEQ ID NO:
- 27, a CDR2L region comprising the amino acid sequence of SEQ ID NO:
- 28, and a CDR3L region comprising the amino acid sequence of SEQ ID NO:
- 20;
- (ii) an CD3-Fab, wherein the CD3-Fab comprises a VH region comprising a CDR1H region comprising the amino acid sequence of SEQ ID NO:
- 1, a CDR2H region comprising the amino acid sequence of SEQ ID NO:
- 2, and a CDR3H region comprising the amino acid sequence of SEQ ID NO:
- 3;
- and a VL region comprising a CDR1L region comprising the amino acid sequence of SEQ ID NO:
- 4, a CDR2L region comprising the amino acid sequence of SEQ ID NO:
- 5, and a CDR3L region comprising the amino acid sequence of SEQ ID NO:
- 6;
- and
- (iii) an Fc part.
15 more elements
A bispecific antibody, comprising:
- (i) a first BCMA-Fab and a second BCMA-Fab, wherein each of the first and second BCMA-Fabs comprises a VH region comprising a CDR1H region comprising the amino acid sequence of SEQ ID NO:
- 21, a CDR2H region comprising the amino acid sequence of SEQ ID NO:
- 22, and a CDR3H region comprising the amino acid sequence of SEQ ID NO:
- 17;
- a VL region comprising a CDR1L region comprising the amino acid sequence of SEQ ID NO:
- 27, a CDR2L region comprising the amino acid sequence of SEQ ID NO:
- 28, and a CDR3L region comprising the amino acid sequence of SEQ ID NO:
- 20;
- a CL domain;
- and a CH1 domain, and wherein
- (a) each of the CL domain of the first and second BCMA-Fabs comprises amino acid substitutions at positions 123 and 124, which are substituted by arginine (R) and lysine (K) respectively (numbering according to Kabat);
- and
- (b) each of the CH1 domain of the first and second BCMA-Fabs comprises amino acid substitutions at positions 147 and 213, which are substituted by glutamic acid (E) (numbering according to EU index of Kabat);
- (ii) an CD3-Fab, wherein the CD3-Fab comprises a VH region comprising the amino acid sequence of SEQ ID NO:
- 1, a CDR2H region comprising the amino acid sequence of SEQ ID NO:
- 2, and a CDR3H region comprising the amino acid sequence of SEQ ID NO:
- 3;
- and a VL region comprising a CDR1L region comprising the amino acid sequence of SEQ ID NO:
- 4, a CDR2L region comprising the amino acid sequence of SEQ ID NO:
- 5, and a CDR3L region comprising the amino acid sequence of SEQ ID NO:
- 6;
- and the VH region and the VL region of the CD3-Fab are replaced by each other;
- and
- (iii) an Fc part,
- wherein the N-terminus of the Fc part is linked to each of the C-terminus of the first BCMA-Fab and the C-terminus of the CD3-Fab, the N-terminus of the CD3-Fab is linked to the C-terminus of the second BCMA-Fab, and the VL region of the CD3-Fab is linked to the CH1 domain of the second BCMA-Fab.
22 more elements
A bispecific antibody, comprising five polypeptides comprising the amino acid sequences of SEQ ID NO:
- 48, SEQ ID NO:
- 55, SEQ ID NO:
- 56, SEQ ID NO:
- 57, and SEQ ID NO:
- 57 respectively.
2 more elements
Dependencies are inferred from the claim text.