Mage-a4 peptide dual t cell engagers
AssigneeCdr-Life AG
InventorsStephanie JUNGMICHEL, Fabian Bert SCHEIFELE, Anna Maria SOBIERAJ, Philipp Robert RICHLE, Hannes MERTEN, Leonardo BORRAS, Christian Valdemar Vinge LEISNER
Life of this patent
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Abstract
Described herein are antigen binding proteins with specificity to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one MAGE-A4 pMHC antigen binding domain. Methods of treating cancer with the same are also described.
Claims24
1-95. (canceled)
A method of treating a MAGE-A4 pMHC-expressing cancer in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an antigen binding protein which specifically binds to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC), wherein the antigen binding protein comprises:
- A:
- an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 10, and
- an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 15:
- B:
- a VH domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 20, and
- a VL domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 25;
- C:
- a VH domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 30, wherein the VH domain comprises a C amino acid at position 44 of SEO ID NO:
- 30, and
- a VL domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 35, wherein the VL domain comprises a C amino acid at position 102 of SEQ ID NO:
- 35;
- or
- D:
- a VH domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 40, wherein the VH domain comprises a Y amino acid at position 47, a R amino acid at position 71, and a N amino acid at position 73 of SEQ ID NO:
- 40, and
- a VL domain comprising an amino acid sequence that is at least about 90%, 95%, 96%, 97%, 98% or 100% identical to the amino acid sequence of SEQ ID NO:
- 45.
99-102. (canceled)
A method of treating a MAGE-A4 pMHC-expressing cancer in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a multispecific antigen binding protein which specifically binds to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC), wherein the multispecific antigen binding protein comprises:
- a) a first antigen binding domain which specifically binds to CD3;
- b) a second antigen binding domain which specifically binds to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC), said second antigen binding domain comprising:
- b1) an antibody heavy chain variable (VH) domain comprising an HCDR1 amino acid sequence of SNYAMS (SEQ ID NO:
- 11), an HCDR2 amino acid sequence of IVSSGGTTYYAX1X2X3KG (SEQ ID NO:
- 6), wherein X1 corresponds to amino acid S or D, X2 corresponds to amino acid W or S, and X3 corresponds to amino acid A or V, and an HCDR3 amino acid sequence of DLYYGPX4TX5YX6X7X8NL (SEQ ID NO:
- 7), wherein X4 corresponds to amino acid T, N, or S, X5 corresponds to amino acid D or is absent, X6 corresponds to amino acid S or F, X7 corresponds to amino acid A or V, and X8 corresponds to amino acid F or A;
- and
- b2) an antibody light chain variable (VL) domain comprising an LCDR1 amino acid sequence of TADTLSRSYAS (SEQ ID NO:
- 16), an LCDR2 amino acid sequence of RDTSRPS (SEQ ID NO:
- 17), and an LCDR3 amino acid sequence of ATX9X10X11SGSNFQX12 (SEQ ID NO:
- 8), wherein X9 corresponds to amino acid S or R, X10 corresponds to amino acid D or P, X11 corresponds to amino acid G, S, or F, and X12 corresponds to amino acid L or A;
- and
- c) a third antigen binding domain which specifically binds to MAGE-A4 pMHC, said third antigen binding domain comprising:
- c1) a VH domain comprising an HCDR1 amino acid sequence of SNYAMS (SEQ ID NO:
- 11), an HCDR2 amino acid sequence of IVSSGGTTYYAX1X2X3KG (SEQ ID NO:
- 6), wherein X1 corresponds to amino acid S or D, X2 corresponds to amino acid W or S, and X3 corresponds to amino acid A or V, and an HCDR3 amino acid sequence of DLYYGPX4TX5YX6X7X8NL (SEQ ID NO:
- 7), wherein X4 corresponds to amino acid T, N, or S, X5 corresponds to amino acid D or is absent, X6 corresponds to amino acid S or F, X7 corresponds to amino acid A or V, and X8 corresponds to amino acid F or A;
- and
- c2) a VL domain comprising an LCDR1 amino acid sequence of TADTLSRSYAS (SEQ ID NO:
- 16), an LCDR2 amino acid sequence of RDTSRPS (SEQ ID NO:
- 17), and an LCDR3 amino acid sequence of ATX9X10X11SGSNFQX12 (SEQ ID NO:
- 8), wherein X9 corresponds to amino acid S or R, X10 corresponds to amino acid D or P, X11 corresponds to amino acid G, S, or F, and X12 corresponds to amino acid L or A.
A method of treating a MAGE-A4 pMHC-expressing cancer in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a multispecific antigen binding protein binding to GVYDGREHTV (SEQ ID NO:
- 3) HLA-A*02 complex and to CD3, said multispecific antigen binding protein comprising:
- (i) a first polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 9, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 9, and a second polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 14, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 14;
- (ii) a first polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 19, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 19, and a second polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 24, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 24;
- (iii) a first polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 29, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 29, and a second polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 34, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 34;
- or
- (iv) a first polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 39, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 39, and a second polypeptide chain comprising an amino acid sequence set forth in SEQ ID NO:
- 44, or a variant thereof being at least 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:
- 44.
Dependencies are inferred from the claim text.