Binding molecules for BCMA and CD3

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

BISPECIFIC T CELL ENGAGING ANTIBODY CONSTRUCTS

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to a target cell surface antigen, a second domain binding to an extracellular epitope of the human and/or the CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same. 1. An antibody construct comprising at least three domains , wherein:a first domain binds to a target cell surface antigen,{'i': 'Macaca', 'a second domain binds to an extracellular epitope of the human and/or the CD3ε chain; and'}a third domain comprises two polypeptide monomers, each comprising a hinge, a CH2 and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker.2. The antibody construct of claim 1 , wherein the antibody construct is a single chain antibody construct.3. The antibody construct of claim 1 , wherein said third domain comprises in an amino to carboxyl order:hinge-CH2-CH3-linker-hinge-CH2-CH3.4. The antibody construct of claim 1 , wherein each of said polypeptide monomers has an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of: SEQ ID NOs: 17-24.5. The antibody construct of claim 4 , wherein each of said polypeptide monomers has an amino acid sequence selected from the group consisting of SEQ ID NOs: 17-24.6. The antibody construct of claim 1 , wherein the CH2 domain comprises an intra domain cysteine disulfide bridge.7. The antibody construct of claim 1 , wherein(i) the first domain comprises two antibody variable domains and the second domain comprises two antibody variable domains;(ii) the first domain comprises one antibody variable domain and the second domain comprises two antibody variable domains;(iii) the first domain ...

ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. A bispecific antibody construct comprising a first binding domain which binds to human and macaque epidermal growth factor receptor VIII (EGFRVIII) on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell , wherein the first binding domain comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 157 and a polypeptide comprising the amino acid sequence of SEQ ID NO: 158.2. The antibody construct according to claim 1 , wherein the antibody construct is in a format selected from the group consisting of (scFv) claim 1 , scFv-single domain mAb claim 1 , diabodies and oligomers of those formats.3Callithrix jacchus, Saguinus OedipusSaimiri sciureus. The antibody construct according to claim 1 , wherein the second binding domain binds to human CD3 epsilon and to or CD3 epsilon.4. The antibody construct according to claim 1 , comprising:(a) a polypeptide comprising in the following order starting from the N-terminus:a polypeptide comprising the amino acid sequence of SEQ ID NO: 159;a peptide linker comprising the amino acid sequence selected from any one of SEQ ID NOs: 1-9; anda polypeptide comprising the amino acid sequence selected from of: SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 37, SEQ ID NO: 46, SEQ ID NO: 55, SEQ ID NO: 64, SEQ ID NO: 73, SEQ ID NO: 82, SEQ ID NO: 91, ...

Pharmaceutical compositions with resistance to soluble CEA

The present disclosure relates to a bispecific single chain antibody which has a first binding domain specifically binding to human CD3, and a second binding domain specifically binding to human CEA, where the second binding domain comprises at least a part of the CDR-H3 or the complete CDR-H3 of murine monoclonal antibody A5B7, a pharmaceutical composition comprising the bispecific single chain antibody, and methods for the treatment of an epithelial tumor in a human with the pharmaceutical compositions containing the bispecific single chain antibody. Furthermore, processes for the production of the pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CEA antigen are disclosed.

ANTIBODY CONSTRUCTS FOR MSLN AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human MSLN on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1Macaca fascicularis. A bispecific antibody construct comprising a first binding domain which binds to human and macaque mesothelin (MSLN) on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell , wherein the first binding domain binds to an epitope of MSLN which is comprised within an MSLN polypeptide or variant comprising the amino acid sequence of SEQ ID NO: 231 , 232 , or 233 and further binds to MSLN comprising the amino acid sequence of SEQ ID NO: 234.2Callithrix jacchus, Saguinus OedipusSaimiri sciureus. The antibody construct according to claim 1 , wherein the second binding domain binds to human CD3 epsilon and to or CD3 epsilon.3. The antibody construct according to claim 1 , wherein the antibody construct is in a format selected from the group consisting of: (scFv) claim 1 , scFv-single domain mAb claim 1 , diabodies and oligomers of those formats.4. The antibody construct according to claim 1 , wherein the first binding domain binds to an epitope of MSLN which is comprised within the region of the human MSLN polypeptide comprising the amino acid sequence selected from the group consisting of: SEQ ID NO: 244 claim 1 , SEQ ID NO: 245 and SEQ ID NO: 241.5. The antibody construct according to claim 4 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim ...

Cross-species-specific psmaxcd3 bispecific single chain antibody

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

ANTIBODY CONSTRUCTS FOR DLL3 AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. A bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell and at least macaque CD3 , wherein the first binding domain binds to an epitope of DLL3 within the amino acid sequence of SEQ ID NO: 260.2Macaca fascicularis. The antibody construct according to claim 1 , wherein the first binding domain further binds to macaque DLL3 claim 1 , preferably to DLL3.3Callithrix jacchus, Saguinus OedipusSaimiri sciureus. The antibody construct according to claim 1 , wherein the second binding domain binds to human CD3 epsilon and to or CD3 epsilon.4. The antibody construct according to claim 1 , wherein the antibody construct is in a format selected from the group consisting of: (scFv) claim 1 , scFv-single domain mAb claim 1 , diabodies and oligomers of the foregoing formats.5. The antibody construct according to claim 1 , wherein the first binding domain binds to an epitope of DLL3 within the amino acid sequence of SEQ ID NO: 258.6. The antibody construct according to claim 5 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 5 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 5 , CDR-L2 and CDR-L3 selected from the group consisting of:a) CDR-H1 comprising the amino ...

Antibody constructs for influenza M2 and CD3

The present invention relates to an antibody construct comprising a first human binding domain specific for the extracellular part of the influenza envelope protein M2 (M2e) and a second domain specific for CD3. Moreover, the invention provides a nucleic acid molecule encoding the antibody construct, a vector comprising said nucleic acid molecule and a host cell transformed or transfected with said nucleic acid molecule or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a pharmaceutical composition comprising said antibody construct, a medical use/method of treatment relating to said antibody construct, and a kit comprising said antibody construct.

ANTIBODY CONSTRUCTS FOR FLT3 AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human FLT3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

PSMA and CD3 Bispecific T Cell Engaging Antibody Constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to PSMA, a second domain binding to an extracellular epitope of the human and the CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same. 1. An antibody construct comprising:a first domain which binds to prostate-specific membrane antigen (PSMA),{'i': 'Macaca', 'a second domain which binds to an extracellular epitope of the human and the CD3ε chain; and'}a third domain which comprises two polypeptide monomers, each comprising a hinge, a CH2 domain and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker.2. The antibody construct of claim 1 , wherein the antibody construct is a single chain antibody construct.3. The antibody construct of claim 1 , wherein said third domain comprises in an amino to carboxyl order:hinge-CH2-CH3-linker-hinge-CH2-CH3.4. The antibody construct of claim 1 , wherein each of said polypeptide monomers has an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of: SEQ ID NOs: 17-24.5. The antibody construct of claim 4 , wherein each of said polypeptide monomers has an amino acid sequence selected from the group consisting of SEQ ID NOs: 17-24.6. The antibody construct of claim 1 , wherein the CH2 domain comprises an intra domain cysteine disulfide bridge.7. The antibody construct of claim 1 , wherein(i) the first domain comprises two antibody variable domains and the second domain comprises two antibody variable domains;(ii) the first domain comprises one antibody variable domain and the second domain comprises two antibody variable domains;(iii) the first domain comprises two antibody variable ...

Antibody constructs for CDH19 and CD3

The present invention provides a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds a human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising the polynucleotide and a host cell transformed or transfected with the polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of the antibody construct in the treatment of melanoma, and a kit comprising the antibody construct.

ANTIBODY CONSTRUCTS FOR CD70 AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. A bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell and at least macaque CD3.2. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 claim 1 , wherein{'sub': 1', '2', '3', '1', '2', '3, 'said CDR-H1 comprises the amino acid sequence XYXMX(SEQ ID NO: 1869), wherein Xis S, T or V, Xis A or S, and Xis S or N;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '1', '2', '3', '4', '5', '6', '7, 'said CDR-H2 comprises the amino acid sequence XISXSGGXXXXAESVXG (SEQ ID NO: 1870), wherein Xis A, Y, V, L, or T, Xis G or S, Xis R, Y, S, G or I, Xis T, I, P, or A, Xis F, Y, N, Q or D, Xis Y or F, and Xis E, K or Q;'}{'sub': 1', '2', '3', '1', '2', '3, 'said CDR-H3 comprises the amino acid sequence XDYSNYXXFDY (SEQ ID NO: 1871), wherein Xis H, G or V, Xis P, A, L or F, and Xis Y or F;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '1', '2', '3', '4', '5', '6', '7', '8, 'said CDR-L1 comprises the amino acid sequence RAXQXXXXXXLX(SEQ ID NO: 1872), wherein Xis S or G, Xis S or G, Xis I or V, Xis R, S or no amino acid, Xis S or G, Xis S, N, T or D, Xis Y or no ...

Cross-species-specific PSMAxCD3 bispecific single chain antibody

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

Antibody neutralizers of human granulocyte macrophage colony stimulating factor

The present invention relates to a human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF.

PHARMACEUTICAL COMPOSITIONS WITH RESISTANCE TO SOLUBLE CEA

The present disclosure relates to a bispecific single chain antibody which has a first binding domain specifically binding to human CD3, and a second binding domain specifically binding to human CEA, where the second binding domain comprises at least a part of the CDR-H3 or the complete CDR-H3 of murine monoclonal antibody A5B7, a pharmaceutical composition comprising the bispecific single chain antibody, and methods for the treatment of an epithelial tumor in a human with the pharmaceutical compositions containing the bispecific single chain antibody. Furthermore, processes for the production of the pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CEA antigen are disclosed. 1. A bispecific single chain antibody comprising(a) a first binding domain specifically binding to human CD3, and{'sub': L', 'H, '(b) a second binding domain specifically binding to human CEA, wherein said second binding domain comprises a variable light chain (V) region and a variable heavy chain (V) region;'}{'sub': 'L', 'wherein said (V) region comprises a CDR-L1 having the amino acid sequence “TLRRGINVGAYSIY” (SEQ ID NO: 73), a CDR-L2 having the amino acid sequence “YKSDSDKQQGS” (SEQ ID NO: 72), and a CDR-L3 having the amino acid sequence “MIWHSGASAV” (SEQ ID NO: 71);'}{'sub': H', '1', '2', '3', '4', '1', '2', '3', '4, 'and wherein said (V) region comprises a CDR-H1 having the amino acid sequence “SYWMH” (SEQ ID NO: 68), a CDR-H2 having the amino acid sequence “FILNKANGGTTEYAASVKG” (SEQ ID NO: 145), and a CDR-H3 having the amino acid sequence “DXXXXFYFDY” (SEQ ID NO: 65), wherein “X”, “X”, “X” or “X” represents any amino acid residue, and the amino acid residue “D” corresponds to Kabat position 95 of CDR-H3 of murine monoclonal antibody A5B7, and the amino acid residues “FYFDY” correspond to Kabat positions 100, 100a, 100b, 101, and 102, respectively, of ...

BCMA AND CD3 BISPECIFIC T CELL ENGAGING ANTIBODY CONSTRUCTS

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

ANTIBODY NEUTRALIZERS OF HUMAN GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR

The present invention relates to a human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF. 1. A human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF.2. The human monoclonal antibody or fragment thereof according to having a equilibrium disassociation constant Kof between about 4×10M and about 0.04×10M.3. The human monoclonal antibody or fragment thereof according to claim 1 , wherein said human monoclonal antibody or fragment thereof specifically binds to an epitope of primate GM-CSF comprising amino acids 23-27 (RRLLN) of SEQ ID NO: 49 and/or amino acids 65-77 (GLR/QGSLTKLKGPL) of SEQ ID NO: 49 or 50.4. The human monoclonal antibody or fragment thereof according to comprising in its heavy chain variable region a CDR3 having an amino acid sequence chosen from the group consisting of SEQ ID NOs: 1 claim 1 , 3-13 and 56.5. The human monoclonal antibody or fragment thereof according to or comprising in its light chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 16 claim 1 , a CDR2 having an amino acid sequence as set out in SEQ ID NO: 17 claim 1 , and a CDR3 having an amino acid sequence as set out in SEQ ID NO: 18.6. The human monoclonal antibody or fragment thereof according to comprising in its heavy chain variable region a CDR 1 region comprising an amino acid sequence as set out in SEQ ID NO: 14 claim 5 , a CDR2 region having an amino acid sequence as set out in SEQ ID NO: 15.7. The human monoclonal antibody or fragment thereof according to wherein the primate GM-CSF is a human GM-CSF.8. The human monoclonal antibody or fragment thereof according wherein the primate is non-human primate.9. The human monoclonal fragment according to wherein said fragment is an scFv claim 1 , a single domain antibody claim 1 , an Fv claim 1 , a VHH antibody claim 1 , a diabody claim 1 , a tandem diabody claim 1 , a Fab claim 1 , a Fab′ or a F(ab ...

CROSS-SPECIES-SPECIFIC BISPECIFIC BINDERS

The present invention relates to a polypeptide comprising a first human binding domain capbable of binding to an epitope of human and non-chimpanzee CD3ε (epsilon) chain and a second binding domain capable of binding to EGFR, Her2/neu or IgE of a human and/or a non-chimpanzee primate as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acid sequences encoding the polypeptide, to vectors comprising the nucleic acid sequences and to host cells comprising the nucleic acid sequences or vectors containing the nucleic acid sequences. In another aspect, the invention provides for a pharmaceutical composition comprising the polypeptide and methods of medical treatment or use of the polypeptide. 1Callithrix jacchus, Saquinus oedipusSaimiri sciureus. A polypeptide comprising an antibody comprising a first binding domain , which is an antigen-interaction site , capable of binding to an epitope of human and or CD3ε (epsilon) chain , wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NO: 2 , 4 , 6 , or 8 and comprises at least the amino acid sequence Gln-Asp-Gly-Asn-Glu , and a second binding domain capable of binding to EGFR , Her2/neu or IgE of a human and/or a non-chimpanzee primate.2. The polypeptide according to claim 1 , wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NO: 2 claim 1 , 4 claim 1 , 6 claim 1 , and 8 and comprises at least the amino acid sequence Gln-Asp-Gly-Asn-Glu.3. The polypeptide according to claim 1 , wherein the first binding domain comprises a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from:(a) CDR-L1 as depicted in SEQ ID NO:27, CDR-L2 as depicted in SEQ ID NO:28 and CDR-L3 as depicted in SEQ ID NO:29;(b) CDR-L1 as depicted in SEQ ID NO:117, CDR-L2 as depicted in SEQ ID NO:118 and CDR-L3 as depicted in SEQ ID NO:119; and(c) CDR-L1 as depicted in SEQ ID NO:153, CDR-L2 as ...

COMPOSITIONS COMPRISING CROSS-SPECIES-SPECIFIC ANTIBODIES AND USES THEREOF

The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases. 1. A bispecific single chain antibody which comprises(i) a first binding domain binding to an epitope of human and non-chimpanzee primate CD3, and(ii) a second binding domain binding to a cell surface antigen,wherein the epitope comprises the amino acid sequence “FSEXE” (SEQ ID NO. 204), wherein “X” represents L (Leucine) or M (Methionine).2. (canceled)3. The bispecific single chain antibody of claim 1 , wherein said first binding domain is located C-terminally or N-terminally to the second binding domain.4. The bispecific single chain antibody of claim 1 , wherein the second binding domain binds to a human cell surface antigen and to the non-chimpanzee primate homolog of said cell surface antigen.5. The bispecific single chain antibody of claim 1 , wherein the cell surface antigen is a tumor antigen.6. The bispecific single chain antibody of claim 1 , wherein the first binding domain comprises a VH region having an amino acid sequence as shown in any of SEQ ID NOs. 2 claim 1 , 110 or 6.7. The bispecific single chain antibody of claim 1 , wherein the ...

CROSS-SPECIES-SPECIFIC PSMAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule which is at least bispecific comprising a first and a second binding domain , wherein(a) the first binding domain is capable of binding to epitope cluster 3 of BCMA (CQLRCSSNTPPLTCQRYC); and(b) the second binding domain is capable of binding to the T cell CD3 receptor complex; andwherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002.2. The binding molecule according to claim 1 , wherein the first binding domain is further capable of binding to epitope cluster 3 of macaque BCMA (CQLRCSSTPPLTCQRYC).3. The binding molecule according to wherein the second binding domain is capable of binding to CD3 epsilon.4. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.5. The binding molecule according to claim 1 , wherein the first and/or the second binding domain are derived from an antibody.6. The binding molecule according to claim 5 , which is selected from the group consisting of (scFv) claim 5 , (single domain mAb) claim 5 , scFv-single domain mAb claim 5 , diabodies and oligomers thereof.7. The binding molecule according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and ...

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 2. The binding molecule of claim 1 , wherein the first binding domain is not capable of binding to the chimeric extracellular domain of BCMA as depicted in SEQ ID NO: 1015.3. The binding molecule according to claim 1 , wherein the first binding domain is further capable of binding to macaque BCMA.4. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to CD3 epsilon.5. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.6. The binding molecule according to claim 1 , wherein the first and/or the second binding domain are derived from an antibody.7. The binding molecule according to claim 6 , which is selected from the group consisting of (scFv) claim 6 , (single domain mAb) claim 6 , scFv-single domain mAb claim 6 , diabodies and oligomers thereof.8. The binding molecule according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from the group consisting of:(a) CDR-H1 as depicted in SEQ ID NO: 231, CDR-H2 as depicted in SEQ ID NO: 232, CDR-H3 as depicted in SEQ ID NO: 233, CDR-L1 as depicted in SEQ ID NO: 234, CDR-L2 as depicted in SEQ ID NO: 235 and CDR-L3 as ...

PREPARATION OF SCFV ANTIBODY FRAGMENTS

The invention relates to methods of preparing antibody fragments. The invention further relates to antibody fragments prepared by these methods. The invention further relates to antibody variable regions comprised in antibody fragments producible by these methods. 115.-. (canceled)16. An antibody fragment obtainable by a method comprising:a) providing a nucleic acid molecule encoding a first antibody variable region or fragment thereof comprised in a source immunoglobulin, wherein the first antibody variable region or fragment thereof is a heavy chain variable region (VH) or a light chain variable region (VL), or a fragment of either of these;b) respectively combining (i) the nucleic acid molecule encoding the first antibody VH or VL region or fragment of either with (ii) a plurality of nucleic acid molecules encoding a diverse population of a second antibody variable region or fragment thereof, wherein the second antibody variable region or fragment thereof is a light chain variable region (VL) or a heavy chain variable region (VH), or a fragment of either of these, whereby a population of combined nucleic acid molecules is obtained;c) introducing the population of combined nucleic acid molecules into a display system chosen from a phage display system, a prokaryotic display system, a eukaryotic display system, or an mRNA display system;d) selecting at least one antibody fragment displayed in (c) and comprising the VH and VL regions, or a fragment of either or both of these, which specifically binds to an antigen of interest; ande) isolating the at least one antibody fragment selected in (d);wherein the nucleic acid molecule encoding the first antibody variable region or fragment thereof or the nucleic acid molecule encoding the second antibody variable region or fragment thereof is operably linked to a nucleic acid molecule encoding an N-terminal, cis-acting amphipathic polypeptide moiety such that said N-terminal, cis-acting amphipathic polypeptide moiety, when ...

PHARMACEUTICAL COMPOSITIONS WITH RESISTANCE TO SOLUBLE CEA

The present disclosure relates to a bispecific single chain antibody which has a first binding domain specifically binding to human CD3, and a second binding domain specifically binding to human CEA, where the second binding domain comprises at least a part of the CDR-H3 or the complete CDR-H3 of murine monoclonal antibody A5B7, a pharmaceutical composition comprising the bispecific single chain antibody, and methods for the treatment of an epithelial tumor in a human with the pharmaceutical compositions containing the bispecific single chain antibody. Furthermore, processes for the production of the pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CEA antigen are disclosed. 1. A bispecific single chain antibody which comprises:(a) a first binding domain specifically binding to human CD3, and(b) a second binding domain specifically binding to human CEA,{'sub': 2', '3', '1', '2', '3', '4, 'sup': ')', 'wherein said second binding domain comprises at least the amino acid sequence “DXiXXQ FYFDY” (SEQ ID NO. 65), wherein “X”, “X”, “X” or “X” represents any amino acid residue, and the amino acid residue “D” corresponds to Kabat position 95 of CDR-H3 of murine monoclonal antibody A5B7 and the amino acid residues “FYFDY” correspond to Kabat positions 100, 100a, 100b, 101, and 102, respectively, of CDR-H3 of murine monoclonal antibody A5B7.'}2. The bispecific single chain antibody of claim 1 , wherein{'sub': '1', '“X” represents “R” (Arginine), “F” (Phenylalanine), “M” (Methionine), “E” (Glutamic acid), or “T” (Threonine);'}{'sub': '2', '“X” represents “G” (Glycine), “Y” (Tyrosine), “A” (Alanine), “D” (Aspartic acid), or “S” (Serine);'}{'sub': '3', '“X” represents “L” (Leucine), “F” (Phenylalanine), “M” (Methionine), “E” (Glutamic acid), or “T” (Threonine); and'}{'sub': '4', '“X” represents “R” (Arginine), “Y” (Tyrosine), “A” (Alanine), ...

Antibody Constructs For CDH19 and CD3

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 114-. (canceled)15. A method for treating or ameliorating a melanoma disease , comprising the step of administering to a subject in need thereof a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell ,wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(a)(i) CDR-H1 as set forth in SEQ ID NO: 14, CDR-H2 as set forth in SEQ ID NO: 15, CDR-H3 as set forth in SEQ ID NO: 16, CDR-L1 as set forth in SEQ ID NO: 17, CDR-L2 as set forth in SEQ ID NO: 18 and CDR-L3 as set forth in SEQ ID NO: 19;(a)(ii) CDR-H1 as set forth in SEQ ID NO: 27, CDR-H2 as set forth in SEQ ID NO: 28, CDR-H3 as set forth in SEQ ID NO: 29, CDR-L1 as set forth in SEQ ID NO: 30, CDR-L2 as set forth in SEQ ID NO: 31 and CDR-L3 as set forth in SEQ ID NO: 32;(a)(iii) CDR-H1 as set forth in SEQ ID NO: 40, CDR-H2 as set forth in SEQ ID NO: 41, CDR-H3 as set forth in SEQ ID NO: 42, CDR-L1 as set forth in SEQ ID NO: 43, CDR-L2 as set forth in SEQ ID NO: 44 and CDR-L3 as set forth in SEQ ID NO: 45;(a)(iv) CDR-H1 as set forth in SEQ ID NO: 53, CDR-H2 as set forth in SEQ ID NO: 54, CDR-H3 as set ...

MAGEB2 BINDING CONSTRUCTS

The present invention relates to antibody constructs comprising a domain which binds to a MAGEB2 peptide complexed with an HLA and optionally, another domain which binds to CD3. Moreover, the invention provides polynucleotides encoding the antibody constructs, vectors comprising said polynucleotides and host cells transformed or transfected with said polynucleotides or vectors. Furthermore, the invention provides processes for producing the antibody constructs of the invention, medical uses of said antibody constructs, and kits comprising said antibody constructs. 1. An isolated antibody construct that binds to an epitope comprising both a MAGEB2 peptide (SEQ ID NO: 1) and an HLA-A2/MHC , wherein the antibody construct comprises at least one of the following heavy chain amino acid residues: Ser30 , Ser31 , His32 , Tyr32 , Ala33 , Ser52 , Gly53 , Ser54 , Gly56 , Gly57 , Tyr59 , Lys100 , Gly101 , Val102 , His103 , Leu104 , or Gly105.2. The antibody of claim 1 , further comprising at least one of the following light chain amino acid residues: Asn25 claim 1 , Asn26 claim 1 , Gly28 claim 1 , Ser29 claim 1 , Lys30 claim 1 , Ser31 claim 1 , His33 claim 1 , Tyr48 claim 1 , Asp49 claim 1 , Asp50 claim 1 , Asn51 claim 1 , Asp52 claim 1 , Arg53 claim 1 , Asn65 claim 1 , Phe66 claim 1 , Ser66 claim 1 , Gly67 claim 1 , Trp90 claim 1 , Tyr92 claim 1 , Arg93 claim 1 , Leu95 claim 1 , Gln95.3. An isolated antibody construct that binds to an epitope comprising a pMAGE-HLA claim 1 , wherein the antibody construct binds to at least one of the following MAGEB2 peptide (SEQ ID NO: 1) residues: Asp4 claim 1 , Gly5 claim 1 , Glu6 claim 1 , Glu7 claim 1 , His8 claim 1 , Ser9 claim 1 , or Val10.4. The isolated antibody construct of claim 3 , wherein the antibody construct further binds to at least one of the following HLA-A2 residues: Arg65 claim 3 , Lys66 claim 3 , Ala69 claim 3 , Gln72 claim 3 , Thr73 claim 3 , Val76 claim 3 , Lys146 claim 3 , Ala149 claim 3 , Ala150 claim 3 , His151 ...

ANTIBODY CONSTRUCTS FOR CDH19 AND CD3

The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. An isolated multispecific antibody construct or an oligomer thereof comprising a first binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell , wherein the first binding domain comprises a VH region comprising CDR-H1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 , CDR-L2 and CDR-L3 selected from the group consisting of:(a) CDR-H1 as set forth in SEQ ID NO: 124, CDR-H2 as set forth in SEQ ID NO: 125, CDR-H3 as set forth in SEQ ID NO: 126, CDR-L1 as set forth in SEQ ID NO: 292, CDR-L2 as set forth in SEQ ID NO: 293 and CDR-L3 as set forth in SEQ ID NO: 294;(b) CDR-H1 as set forth in SEQ ID NO: 130, CDR-H2 as set forth in SEQ ID NO: 131, CDR-H3 as set forth in SEQ ID NO: 132, CDR-L1 as set forth in SEQ ID NO: 298, CDR-L2 as set forth in SEQ ID NO: 299 and CDR-L3 as set forth in SEQ ID NO: 300;(c) CDR-H1 as set forth in SEQ ID NO: 136, CDR-H2 as set forth in SEQ ID NO: 137, CDR-H3 as set forth in SEQ ID NO: 138, CDR-L1 as set forth in SEQ ID NO: 304, CDR-L2 as set forth in SEQ ID NO: 305 and CDR-L3 as set forth in SEQ ID NO: 306;(d) CDR-H1 as set forth in SEQ ID NO: 142, CDR-H2 as set forth in SEQ ID NO: 143, CDR-H3 as set forth in SEQ ID NO: 144, CDR-L1 as set forth in SEQ ID NO: 310, CDR-L2 as set forth in SEQ ID NO: 311 and CDR-L3 as ...

Binding molecules for bcma and cd3

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster3 of BCMA, and the second binding domain is capable of binding to the Tcell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

CROSS-SPECIES-SPECIFIC SINGLE DOMAIN BISPECIFIC SINGLE CHAIN ANTIBODY

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain consisting of one antibody variable domain capable of binding to an epitope of the human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to an epitope of a human and a non-chimpanzee primate tumor target antigen. The invention further relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3ε (epsilon) chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain consisting of one antibody variable domain capable of binding to an epitope of a human and a non-chimpanzee primate tumor target antigen. The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule. 115-. (canceled)16. A nucleic acid encoding a bispecific single chain antibody molecule comprising a first binding domain which binds to an epitope of a human CD3 epsilon (CD3ε) chain , wherein the epitope is part of the amino acid sequence set forth in SEQ ID NO: 2 , 4 , 6 , or 8 , and comprises at least the amino acid sequence Gln-Asp-Gly-Asn-Glu (QDGNE; SEQ ID NO: 430) , and a second binding domain comprising an antibody variable domain that is cross-species specific and binds to an epitope of a human and a non-chimpanzee primate tumor target antigen , wherein the first binding domain is a VHH domain and comprises CDR 1 of SEQ ID NO: 398 , CDR 2 of SEQ ID NO: ...

Antibody constructs for CDH19 and CD3

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. A bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell ,wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(a) CDR-H1 as depicted in SEQ ID NO: 14, CDR-H2 as depicted in SEQ ID NO: 15, CDR-H3 as depicted in SEQ ID NO: 16, CDR-L1 as depicted in SEQ ID NO: 17, CDR-L2 as depicted in SEQ ID NO: 18 and CDR-L3 as depicted in SEQ ID NO: 19;CDR-H1 as depicted in SEQ ID NO: 27, CDR-H2 as depicted in SEQ ID NO: 28, CDR-H3 as depicted in SEQ ID NO: 29, CDR-L1 as depicted in SEQ ID NO: 30, CDR-L2 as depicted in SEQ ID NO: 31 and CDR-L3 as depicted in SEQ ID NO: 32;CDR-H1 as depicted in SEQ ID NO: 40, CDR-H2 as depicted in SEQ ID NO: 41, CDR-H3 as depicted in SEQ ID NO: 42, CDR-L1 as depicted in SEQ ID NO: 43, CDR-L2 as depicted in SEQ ID NO: 44 and CDR-L3 as depicted in SEQ ID NO: 45;CDR-H1 as depicted in SEQ ID NO: 53, CDR-H2 as depicted in SEQ ID NO: 54, CDR-H3 as depicted in SEQ ID NO: 55, CDR-L1 as depicted in SEQ ID NO: 56, CDR-L2 as depicted in SEQ ID NO: 57 and CDR-L3 as depicted in SEQ ID NO: 58;CDR-H1 as depicted in SEQ ID NO: 66, CDR-H2 as depicted in ...

LONG LIFE POLYPEPTIDE BINDING MOLECULES

The present invention relates to a binding molecule comprising at least three domains comprised in at least one polypeptide chain, wherein the first binding domain is a binding domain which is capable of binding to a cell surface molecule on a target cell, the second binding domain is a binding domain which is capable of binding to the T cell CD3 receptor complex, and the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule comprising at least three binding domains comprised in at least one polypeptide chain , wherein(a) the first domain is a binding domain which is capable of binding to a cell surface molecule on a target cell; and(b) the second domain is a binding domain which is capable of binding to the T cell CD3 receptor complex; and(c) the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain.2. The binding molecule according to claim 1 , wherein the three domains are on one polypeptide in the order from the N-terminus to the C-terminusthe first binding domain;the second binding domain; andthe third binding domain.3. The binding molecule according to or claim 1 , wherein the third binding of the binding molecule is an scFv or single domain antibody.4. The binding molecule according to any of to claim 1 , wherein(a) the first binding domain is capable of binding to the cell surface molecule on a human and a non-human primate cell;(b) the second binding ...

ANTIBODY CONSTRUCTS FOR INFLUENZA M2 AND CD3

The present invention relates to an antibody construct comprising a first human binding domain specific for the extracellular part of the influenza envelope protein M2 (M2e) and a second domain specific for CD3. Moreover, the invention provides a nucleic acid molecule encoding the antibody construct, a vector comprising said nucleic acid molecule and a host cell transformed or transfected with said nucleic acid molecule or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a pharmaceutical composition comprising said antibody construct, a medical use/method of treatment relating to said antibody construct, and a kit comprising said antibody construct. 1. An antibody construct comprising:(a) a first human binding domain specific for the extracellular part of the influenza envelope protein M2 (M2e), characterized by a CDR-H1 as depicted in SEQ ID NO: 1, a CDR-H2 as depicted in SEQ ID NO: 2, a CDR-H3 as depicted in SEQ ID NO: 3, a CDR-L1 as depicted in SEQ ID NO: 4, a CDR-L2 as depicted in SEQ ID NO: 5, and a CDR-L3 as depicted in SEQ ID NO: 6; and(b) a second binding domain specific for CD3.2. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region selected from the group consisting of VH regions as depicted in SEQ ID NO: 8 claim 1 , 16 claim 1 , 24 claim 1 , 32 claim 1 , 40 claim 1 , 48 claim 1 , 56 claim 1 , 64 claim 1 , and 72.3. The antibody construct according to or claim 1 , wherein the first binding domain comprises a VL region selected from the group consisting of VL regions as depicted in SEQ ID NO: 10 claim 1 , 18 claim 1 , 26 claim 1 , 34 claim 1 , 42 claim 1 , 50 claim 1 , 58 claim 1 , 66 claim 1 , and 74.4. The antibody construct according to any one of the preceding claims claim 1 , wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of pairs of a VH region and a VL region as depicted in SEQ ...

METHOD FOR TREATING GLIOBLASTOMA OR GLIOMA WITH ANITBODY CONSTRUCTS EGFRVIII AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 126.-. (canceled)27. A chimeric human/murine BCMA extracellular domain consisting of SEQ ID NO: 1009. The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.BCMA (B-cell maturation antigen, TNFRSF17, CD269) is a transmembrane protein belonging to the TNF receptor super family. BCMA is originally reported as an integral membrane protein in the Golgi apparatus of human mature B lymphocytes, i.e., as an intracellular protein (Gras et al., (1995) International Immunol 7(7):1093-1105) showing that BCMA seems to have an important role during B-cell development and homeostasis. The finding of Gras et al. might be associated with the fact that the BCMA protein that was described ...

BCMA AND CD3 BISPECIFIC T CELL ENGAGING ANTIBODY CONSTRUCTS

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same. 1. An antibody construct comprising:a first domain which binds to BCMA,{'i': 'Macaca', 'a second domain which binds to an extracellular epitope of the human and/or the CD3ε chain; and'}a third domain which comprises two polypeptide monomers, each comprising a hinge, a CH2 domain and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker resulting in an amino to carboxyl order as follows: hinge-CH2-CH3-linker-hinge-CH2-CH3.2. The antibody construct of claim 1 , wherein the antibody construct is a single chain antibody construct.3. (canceled)4. The antibody construct of claim 1 , wherein each of said polypeptide monomers has an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of SEQ ID NOs: 17-24.5. The antibody construct of claim 1 , wherein each of said polypeptide monomers has an amino acid sequence selected from the group consisting of SEQ ID NOs: 17-24.6. The antibody construct of claim 1 , wherein the CH2 domain comprises an intra-domain cysteine disulfide bridge.7. The antibody construct of claim 1 , wherein(i) the first domain comprises two antibody variable domains and the second domain comprises two antibody variable domains;(ii) the first domain comprises one antibody variable domain and the second domain comprises two antibody variable domains;(iii) the first domain comprises two antibody variable domains and the second domain comprises one antibody variable domain; or ...

Antibody Constructs for CLDN18.2 and CD3

The present invention relates to an antibody construct comprising a domain which binds to Claudin 18.2 (CLDN18.2) and another domain which binds to CD3. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for producing the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. An antibody construct comprisinga first domain which binds to CLDN18.2 on the surface of a target cell, anda second domain which binds to human CD3 on the surface of a T cell, wherein the first domain binds to the same epitope of CLDN18.2 as an antibody or antibody construct comprising a domain which binds to CLDN18.2 on the surface of a target cell and which comprises:a) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 121, CDR-H2 as depicted in SEQ ID NO: 122, and CDR-H3 as depicted in SEQ ID NO: 123, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 124, CDR-L2 as depicted in SEQ ID NO: 125 and CDR-L3 as depicted in SEQ ID NO: 126;b) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 133, CDR-H2 as depicted in SEQ ID NO: 134, and CDR-H3 as depicted in SEQ ID NO: 135, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 136, CDR-L2 as depicted in SEQ ID NO: 137 and CDR-L3 as depicted in SEQ ID NO: 138;c) a VH region as depicted in SEQ ID NO: 127, and a VL region as depicted in SEQ ID NO: 128; ord) a VH region as depicted in SEQ ID NO: 139, and a VL region as depicted in SEQ ID NO: 140.2Callithrix jacchusSaimiri sciureus. The antibody construct according to claim 1 , wherein the second domain binds to human CD3 epsilon and to or CD3 epsilon.3. The antibody construct according to claim 1 , whereina) the antibody construct is a single chain antibody construct,b) the first domain is in the format of an ...

PSMA and CD3 Bispecific T Cell Engaging Antibody Constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to PSMA, a second domain binding to an extracellular epitope of the human and the CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same. 121-. (canceled)22. An antibody construct comprising , in amino to carboxyl order:(i) a first single-chain variable fragment (scFv) that binds to human prostate-specific membrane antigen (PSMA) comprising a VH region and a VL region;(ii) a second scFv that binds to human CD3 epsilon (CD3) chain comprising a VH region and a VL region; and(iii) a single chain Fc domain comprising two Fc monomers, each Fc monomer comprising an immunoglobulin hinge region, a CH2 domain, and a CH3 domain, wherein the Fc monomers are fused to each other via a peptide linker.23. The antibody construct of claim 22 , wherein each Fc monomer comprises the hinge region claim 22 , the CH2 domain claim 22 , and the CH3 domain from an IgG1 immunoglobulin.24. The antibody construct of claim 22 , wherein the peptide linker between the two Fc monomers comprises (GlySer)x claim 22 , wherein x is 5 claim 22 , 6 claim 22 , 7 claim 22 , or 8.25. The antibody construct of claim 22 , wherein each Fc monomer comprises a sequence selected from SEQ ID NOs: 17-24.26. The antibody construct of claim 22 , wherein the VH region and VL region of the first scFv and/or the second scFv are human VH and VL regions.27. The antibody construct of claim 22 , wherein the antibody construct comprises in an amino to carboxyl order: the first scFv claim 22 , a first peptide linker claim 22 , the second scFv claim 22 , a second peptide linker claim 22 , and the single chain Fc domain.28. The antibody construct of claim 22 , wherein ...

COMPOSITIONS COMPRISING CROSS-SPECIES-SPECIFIC ANTIBODIES AND USES THEREOF

The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases. 1. A bispecific single chain antibody comprising:(i) a first binding domain binding to a non-chimpanzee primate CD3, and(ii) a second binding domain binding to a cell surface antigen, wherein said first binding domain binds to human and non-chimpanzee primate CD3.2. The bispecific single chain antibody of claim 1 , wherein said first binding domain binds to an epitope of human and non-chimpanzee primate CD3 comprising the amino acid sequence “FSEXE” (SEQ ID NO. 204) claim 1 , wherein “X” represents L (Leucine) or M (Methionine).3. The bispecific single chain antibody of claim 1 , wherein said first binding domain is located C-terminally or N-terminally to the second binding domain.4. The bispecific single chain antibody of claim 1 , wherein the second binding domain binds to a human cell surface antigen and to the non-chimpanzee primate homolog of said cell surface antigen.5. The bispecific single chain antibody of claim 1 , wherein the cell surface antigen is a tumor antigen.6. The bispecific single chain antibody of claim 1 , wherein the first ...

ANTIBODY CONSTRUCTS FOR CDH19 AND CD3

The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. An isolated multispecific antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell.2. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from the group consisting of: CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 252,', 'CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927,', 'CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927,', 'CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 ...

CROSS-SPECIES-SPECIFIC BISPECIFIC BINDERS

The present invention relates to a polypeptide comprising a first human binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 (epsilon) chain and a second binding domain capable of binding to EGFR, Her2/neu or IgE of a human and/or a non-chimpanzee primate as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide. 1. A polypeptide comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon (CD3ε) chain and a second binding domain capable of binding to EGFR , Her2/neu or IgE of a human and/or a non-chimpanzee primate , wherein the epitope is part of an amino acid sequence set forth in SEQ ID NO: 2 , 4 , 6 , or 8.2. The polypeptide of claim 1 , wherein said first binding domain capable of binding to an epitope of the human and non-chimpanzee primate CD3 epsilon (CD3ε) chain is of human origin.3. The polypeptide of claim 1 , wherein the first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3ε chain comprises a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from:(a) CDR-L1 as depicted in SEQ ID NO. 27, CDR-L2 as depicted in SEQ ID NO. 28 and CDR-L3 as depicted in SEQ ID NO. 29;(b) CDR-L1 as depicted in SEQ ID NO. 117, CDR-L2 as depicted in SEQ ID NO. 118 and CDR-L3 as depicted in SEQ ID NO. 119; and(c) CDR-L1 as depicted in SEQ ID NO. 153, CDR-L2 as depicted in SEQ ID NO. 154 and CDR-L3 as depicted in SEQ ID NO. 155.4. The polypeptide of claim 1 , wherein the first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3ε chain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR ...

Antibody Neutralizers of Human Granulocyte Macrophage Colony Stimulating Factor

The present invention relates to a human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF. 113-. (canceled)14. A method of treating an inflammatory or tumorous disease , comprising administering a human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF , wherein the antibody or fragment thereof comprises in its light chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 16 , a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 17 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 18; and comprising in its heavy chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 14 , a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 15 and a CDR3 comprising an amino acid sequence as set out in any of SEQ ID NOS: 1-13 or 56.15. The method according to claim 14 , wherein said inflammatory disease is chosen from the group consisting of rheumatoid arthritis (RA) (including RA which is resistant to treatment with TNF-alpha neutralizers) claim 14 , asthma claim 14 , multiple sclerosis (MS) claim 14 , chronic obstructive pulmonary disease (COPD) claim 14 , Acute Respiratory Distress Syndrome (ARDS) claim 14 , Idiopathic Pulmonary Fibrosis (IPF) claim 14 , Inflammatory Bowel Disease (IBD) claim 14 , uveitis claim 14 , macular degeneration claim 14 , colitis claim 14 , psoriasis claim 14 , Wallerian Degeneration claim 14 , antiphospholipid syndrome (APS) claim 14 , acute coronary syndrome claim 14 , restenosis claim 14 , atherosclerosis claim 14 , relapsing polychondritis (RP) claim 14 , acute or chronic hepatitis claim 14 , failed orthopedic implants claim 14 , glomerulonephritis claim 14 , lupus and autoimmune disorders.16. (canceled)17. The method of claim 14 , wherein said tumorous disease is a cancer.18. The method of claim 17 , wherein said cancer is leukemia claim 17 , ...

BISPECIFIC ANTIBODY CONSTRUCTS FOR CDH3 AND CD3

The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. A bispecific antibody construct comprising a first human binding domain which binds to an epitope cluster of human CDH3 on the surface of a target cell and comprising a second binding domain which binds to human CD3 on the surface of a T cell , wherein the epitope cluster of human CDH3 is comprised within amino acid positions 291-363 (SEQ ID NO: 36) of human CDH3.2. The antibody construct according to claim 1 , wherein the first binding domain binds to an epitope which is comprised within amino acid positions 291-327 (SEQ ID NO: 34) of human CDH3.3. The antibody construct according to claim 1 , wherein the first binding domain binds to an epitope which is comprised within amino acid positions 328-363 (SEQ ID NO: 35) of human CDH3.4. The antibody construct according to claim 3 , wherein the first binding domain also binds to an epitope which is comprised within amino acid positions 404-440 (SEQ ID NO: 390) of human CDH3.5Macaca fascicularis. The antibody construct according to claim 1 , wherein the first binding domain also binds to macaque CDH3 claim 1 , preferably to CDH3.6. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of:a) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 149, a CDR-H2 as depicted in SEQ ID NO: 150, ...

CROSS-SPECIES-SPECIFIC BISPECIFIC BINDERS

The present invention relates to a polypeptide comprising a first human binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon (CD3ε) chain and a second binding domain capable of binding to EGFR, Her2/neu or IgE of a human and/or a non-chimpanzee primate as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide. 1Callithrix jacchus, Saguinus oedipusSaimiri sciureus. A polypeptide comprising a first binding domain which binds to an epitope of human and or CD3 epsilon (CD3ε) chain , wherein the epitope is part of an amino acid sequence comprising SEQ ID NO: 2 , 4 , 6 , or 8 and comprising at least the amino acid sequence Gln-Asp-Gly-Asn-Glu (SEQ ID NO: 509) , and a second binding domain which binds to EGFR , Her2/neu or IgE of a human and/or a non-chimpanzee primate.2. (canceled)3. The polypeptide of claim 1 , wherein the first binding domain comprises (a) CDR-L1 as depicted in SEQ ID NO. 27, CDR-L2 as depicted in SEQ ID NO. 28 and CDR-L3 as depicted in SEQ ID NO. 29;', '(b) CDR-L1 as depicted in SEQ ID NO. 117, CDR-L2 as depicted in SEQ ID NO. 118 and CDR-L3 as depicted in SEQ ID NO. 119; and', '(c) CDR-L1 as depicted in SEQ ID NO. 153, CDR-L2 as depicted in SEQ ID NO. 154 and CDR-L3 as depicted in SEQ ID NO. 155; and, '(i) a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from (a) CDR-H1 as depicted in SEQ ID NO. 12, CDR-H2 as depicted in SEQ ID NO. 13 and CDR-H3 as depicted in SEQ ID NO. 14;', '(b) CDR-H1 as depicted in SEQ ID NO. 30, CDR-H2 as depicted in SEQ ID NO. 31 and CDR-H3 as depicted in SEQ ID NO. 32;', '(c) CDR-H1 as depicted in SEQ ID NO. 48, CDR-H2 as depicted in SEQ ID NO. 49 and CDR-H3 as depicted ...

ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 114-. (canceled)15. A method for treating glioblastoma or glioma , comprising administering to a subject in need thereof an effective amount of a bispecific antibody construct , said antibody construct comprises a first binding domain which binds to human and macaque epidermal growth factor receptor VIII (EGFRVIII) on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell , wherein the first binding domain comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 157 , and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 158.16. The method of claim 15 , wherein said antibody construct is in a format selected from the group consisting of (scFv) claim 15 , diabodies claim 15 , and oligomers thereof.17Callithrix jacchus, Saguinus oedipusSaimiri sciureus. The method of claim 15 , wherein said second binding domain binds to human CD3 epsilon and to or CD3 epsilon claim 15 , and comprises:(i) a VL region comprising: a CDR-L1 comprising the amino acid of SEQ ID NO: 11, a CDR-L2 comprising the amino acid of SEQ ID NO:12, and a CDR-L3 comprising the amino acid of SEQ ID NO:13; and a VH region comprising: a CDR-H1 comprising the amino acid of SEQ ID NO: 14, a CDR-H2 comprising the amino acid of SEQ ID NO:15, and a CDR-H3 ...

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule which is at least bispecific comprising a first and a second binding domain , wherein(a) the first binding domain is capable of binding to epitope cluster 3; and(b) the second binding domain is capable of binding to the T cell CD3 receptor complex; andwherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002, and comprising at least one protein purification tag which is a GST tag, a FLAG tag or a polyhistidine tag; wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(1) CDR-H1 as depicted in SEQ ID NO: 1, CDR-H2 as depicted in SEQ ID NO: 2, CDR-H3 as depicted in SEQ ID NO: 3, CDR-L1 as depicted in SEQ ID NO: 4, CDR-L2 as depicted in SEQ ID NO: 5 and CDR-L3 as depicted in SEQ ID NO: 6;(2) CDR-H1 as depicted in SEQ ID NO: 11, CDR-H2 as depicted in SEQ ID NO: 12, CDR-H3 as depicted in SEQ ID NO: 13, CDR-L1 as depicted in SEQ ID NO: 14, CDR-L2 as depicted in SEQ ID NO: 15 and CDR-L3 as depicted in SEQ ID NO: 16;(3) CDR-H1 as depicted in SEQ ID NO: 21, CDR-H2 as depicted in SEQ ID NO: 22, CDR-H3 as depicted in SEQ ID NO: 23, CDR-L1 as depicted in SEQ ID NO: 24, CDR-L2 as depicted in SEQ ID NO: 25 and CDR-L3 as ...

LONG LIFE POLYPEPTIDE BINDING MOLECULES

The present invention relates to a binding molecule comprising at least three domains comprised in at least one polypeptide chain, wherein the first binding domain is a binding domain which is capable of binding to a cell surface molecule on a target cell, the second binding domain is a binding domain which is capable of binding to the T cell CD3 receptor complex, and the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule comprising at least three binding domains comprised in at least one polypeptide chain , wherein(a) the first domain is a binding domain which is capable of binding to a cell surface molecule on a target cell; and(b) the second domain is a binding domain which is capable of binding to the T cell CD3 receptor complex; and(c) the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain.2. The binding molecule according to claim 1 , wherein the three domains are on one polypeptide in the order from the N-terminus to the C-terminusthe first binding domain;the second binding domain; andthe third binding domain.3. The binding molecule according to claim 1 ,wherein the third binding domain of the binding molecule is an scFv or a single domain antibody.4. The binding molecule according to claim 1 , wherein(a) the first binding domain is capable of binding to the cell surface molecule on a human and a non-human primate cell;(b) the second binding ...

CROSS-SPECIES-SPECIFIC PSMAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain anti-body molecule.

Antibody Constructs for CDH19 and CD3

The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 1. An isolated multispecific antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell.2. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from the group consisting of: CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 252,', 'CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927,', 'CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927,', 'CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 ...

CROSS-SPECIES-SPECIFIC PSMAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule. 1. A method for treating prostate cancer in a subject having prostate cancer expressing prostate-specific membrane antigen (PSMA) comprising administering to the subject an effective amount of a bispecific single chain antibody molecule , wherein the bispecific single chain antibody molecule comprises a first binding domain that specifically binds to human CD3 epsilon chain and a second binding domain that specifically binds to human PSMA.2. The method of claim 1 , wherein at least one of the first binding domain or the second binding domain is a humanized binding domain.3. The method of claim 1 , wherein both the first binding domain and the second binding domain are humanized binding domains.4. The method of claim 1 , wherein the first binding domain is a single chain variable fragment (scFv) comprising a VH region and a VL region.5. The method of claim 4 , wherein the VH and VL regions are arranged in an amino to carboxyl terminal order of VH-VL.6. The method of claim 4 , wherein the first binding domain is positioned toward the carboxyl terminus of the molecule relative to the second binding domain.7. The method of claim 1 , wherein the second binding domain is a single chain variable fragment (scFv) comprising a ...

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule which is at least bispecific comprising a first and a second binding domain , wherein(a) the first binding domain is capable of binding to epitope cluster 3 and to epitope cluster 4 of BCMA; and(b) the second binding domain is capable of binding to the T cell CD3 receptor complex; andwherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002, and epitope cluster 4 of BCMA corresponds to amino acid residues 42 to 54 of the sequence as depicted in SEQ ID NO: 1002.2. The binding molecule of claim 1 , wherein the first binding domain is not capable of binding to the chimeric extracellular domain of BCMA as depicted in SEQ ID NO: 1015.3. The binding molecule according to wherein the first binding domain is further capable of binding to macaque BCMA.4. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to CD3 epsilon.5. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.6. The binding molecule according to claim 1 , wherein the first and/or the second binding domain are derived from an antibody.7. The binding molecule according to claim 6 , which is selected from the group consisting of (scFv) claim 6 , (single ...

ANTIBODY CONSTRUCTS FOR DLL3 AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 128-. (canceled)29. A nucleic acid encoding a bispecific antibody construct comprising a first binding domain which binds to human delta-like 3 (DLL3) on the surface of a target cell and a second binding domain which binds to human and macaque CD3 on the surface of a T cell , wherein the first binding domain binds to an epitope of DLL3 within the amino acid sequence of SEQ ID NO: 258.30. The nucleic acid of claim 29 , wherein the first binding domain further binds to macaque DLL3.31Macaca fascicularis. The nucleic acid of claim 30 , wherein the macaque DLL3 is DLL3.32Callithrix jacchus, Saguinus oedipusSaimiri sciureus. The nucleic acid of claim 29 , wherein the second binding domain binds to human CD3 epsilon and to or CD3 epsilon.33. The nucleic acid of claim 29 , wherein the antibody construct is in a format selected from the group consisting of: (scFv) claim 29 , diabodies and oligomers of the foregoing formats.34. The nucleic acid of claim 29 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 29 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 29 , CDR-L2 and CDR-L3 selected from the group consisting of:a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 31, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 32, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L1 ...

ANTIBODY CONSTRUCTS FOR DLL3 AND CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 128-. (canceled)29. A bispecific antibody construct comprising a first binding domain which binds to human delta-like 3 (DLL3) on the surface of a target cell and a second binding domain which binds to human and macaque CD3 on the surface of a T cell , wherein the first binding domain binds to an epitope of DLL3 within the amino acid sequence of SEQ ID NO: 258 , and wherein the second binding domain comprises a VL region comprising CDR-L1 , CDR-L2 and CDR-L3 and a VH region comprising CDR-H1 , CDR-H2 and CDR-H3 selected from:a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 342, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 343, CDR-L3 comprising the amino acid sequence of SEQ ID NO: 344; CDR-H1 comprising the amino acid sequence of SEQ ID NO: 345, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 346, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 347;b) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 351, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 352, CDR-L3 comprising the amino acid sequence of SEQ ID NO: 353; CDR-H1 comprising the amino acid sequence of SEQ ID NO: 354, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 355, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 356;c) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 360, CDR-L2 comprising the ...

OPTIMIZED CROSS-SPECIES SPECIFIC BISPECIFIC SINGLE CHAIN ANTIBODY CONTRUCTS

The present invention provides to a bispecific single chain antibody construct binding to a target cell surface antigen via a first binding domain and to the T cell surface antigen CD3 via a second binding domain, wherein serum albumin is fused to the C-terminus of the antibody construct. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 2. The antibody construct according to claim 1 , wherein the serum albumin is a human serum albumin or an FcRn binding optimized variant thereof.3. The antibody construct according to claim 1 , wherein the serum albumin comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 4 to 12 and 608 to 628.4. The antibody construct according to claim 1 , wherein the serum albumin is linked to the antibody construct via a peptide linker.5. The antibody construct according to claim 4 , wherein the peptide linker has the amino acid sequence (GGGGS)(SEQ ID NO: 13)wherein n is an integer in the range of 1 to 5.6. The antibody construct according to claim 1 , wherein the second binding domain comprises a VL region having CDR-L1-L3 and a VH region having CDR-H1-H3 selected from the group consisting of:(a) CDR-L1-L3 as depicted in SEQ ID NOs: 14-16 and CDR-H1-H3 as depicted in SEQ ID NOs: 17-19;(b) CDR-L1-L3 as depicted in SEQ ID NOs: 26-28 and CDR-H1-H3 as depicted in SEQ ID NOs: 29-31;(c) CDR-L1-L3 as depicted in SEQ ID NOs: 38-40 and CDR-H1-H3 as depicted in SEQ ID NOs: 41-43;(d) CDR-L1-L3 as depicted in SEQ ID NOs: 50-52 and CDR-H1-H3 as depicted in SEQ ID NOs: 53-55;(e) CDR-L1-L3 as depicted in SEQ ID NOs: 62-64 and CDR-H1-H3 as depicted in SEQ ID NOs: 65-67;(f) CDR-L1-L3 as depicted in SEQ ID ...

Antibody constructs for cdh19 and cd3

The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Cross-species-specific pscaxcd3, cd19xcd3, c-metxcd3, endosialinxcd3, epcamxcd3, igf-1rxcd3 or fapalphaxcd3 bispecific single chain antibody

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to an antigen selected from the group consisting of Prostate Stem Cell Antigen (PSCA), B-Lymphocyte antigen CD19 (CD19), hepatocyte growth factor receptor (C-MET), Endosialin, the EGF-like domain 1 of EpCAM, encoded by exon 2, Fibroblast activation protein alpha (FAP alpha) and Insulin-like growth factor I receptor (IGF-IR or IGF-1R). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

Cross-species-specific bispecific binders

The present invention relates to a polypeptide comprising a first human binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 (epsilon) chain and a second binding domain capable of binding to EGFR, Her2/neu or IgE of a human and/or a non-chimpanzee primate as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide.

Cross-species-specific psmaxcd3 bispecific single chain antibody

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

Cross-species-specific psmaxcd3 bispecific single chain antibody

BINDING MOLECULES FOR BCMA AND CD3

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. (canceled)2. An antibody comprising:a first portion comprising a binding domain that binds to human CD3; anda second portion comprising an amino acid sequence of SEQ ID NO: 732 with not more than 6 amino acid substitutions.3. The antibody of claim 2 , wherein the antibody is human or humanized.4. The antibody of claim 2 , further comprising an IgG framework.5. The antibody of claim 2 , further comprising an Fc constant domain.6. The antibody of claim 2 , wherein the first portion binds to human CD3 with a KD of about 10M or stronger.7. A method of processing a cell culture supernatant comprising:{'sub': '2', 'equilibrating an immobilized metal affinity chromatography column loaded with ZnClwith a buffer consisting of 20 mM sodium phosphate buffer pH 7.2 and 0.1 M NaCl (Buffer A);'}applying 10 ml of 0.2 m filtered cell culture supernatant from cells expressing a soluble BCMA protein comprising a modified histidine tag having the sequence SGHHGGHHGGHH to the immobilized metal affinity chromatography column at a flow rate of 3 ml/min;washing the immobilized metal affinity chromatography column with Buffer A to remove unbound sample;eluting bound protein using a two-step gradient of a buffer consisting of 20 mM sodium phosphate buffer pH 7.2, 0.1 M NaCl, and 0.5 M imidazole (Buffer B) ...

Antibody constructs for CD70 and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Expression-enhanced polypeptides

A composite polypeptide, said composite polypeptide comprising a desired polypeptide and an expression enhancing domain (“EED”), said EED comprising first and second cysteine amino acid residues Cys1 and Cys2, respectively, Cys1 being located closer to the N-terminus of the composite polypeptide molecule than Cys2, wherein Cys1 and Cys2 are separated by a polypeptide linker, said linker—being free of cysteine and proline;—defining a length sufficient to allow Cys1 and Cys2 to engage in an intramolecular disulfide bond with one another; and—having a flexible polypeptide conformation essentially free of secondary polypeptide structure in aqueous solution, wherein at least one of Cys1 and Cys2 is derivatized with a derivatization moiety.

ANTI-CCR8 ANTIBODIES AND USES THEREOF

The present invention provides anti-CCR8 antibodies and antigen-binding fragments thereof, and methods of making and using said anti-CCR8 antibodies and antigen-binding fragments thereof. 1. An antibody that binds to human C—C chemokine receptor type 8 (CCR8) , or an antigen-binding fragment thereof , wherein said antibody or antigen-binding fragment thereof comprises:(a) a heavy chain complementarity-determining region (HCDR) 1 amino acid sequence of SEQ ID NO: 839;(b) an HCDR2 amino acid sequence of SEQ ID NO: 840,(c) an HCDR3 amino acid sequence of SEQ ID NO: 841,{'sub': 1', '1, '(d) a light chain complementarity-determining region (LCDR) 1 amino acid sequence of KSSQSVLYSSNNXNYLA (SEQ ID NO: 1235), wherein Xis K or R,'}(e) an LCDR2 amino acid sequence of SEQ ID NO: 843, and(f) an LCDR3 amino acid sequence of SEQ ID NO: 844.2. The antibody or antigen binding fragment of claim 1 , which comprises an LCDR1 amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 842.3. The antibody or antigen binding fragment of claim 1 , which comprises a heavy chain variable region (HCVR) amino acid sequence of SEQ ID NO: 13 claim 1 , and a light chain variable region (LCVR) comprising the amino acid sequence: DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNXNYLAWYXQKPGQXPKLLIS WASTRESGVPDRFSGSGSGTDFTLTINSLQAEDVAVYYCQQYYSIPITFGGGTKVEIK R (SEQ ID NO: 1236) claim 1 , wherein Xis K or R claim 1 , Xis H or Q claim 1 , and/or Xis S or P.4. The antibody or antigen-binding fragment of claim 1 , which comprises a heavy chain variable region (HCVR) amino acid sequence of SEQ ID NO: 1017 and a light chain variable region (LCVR) amino acid sequence of SEQ ID NO: 1018.5. The antibody or antigen-binding fragment of claim 1 , which comprises a heavy chain (HC) amino acid sequence of SEQ ID NO: 1125 or SEQ ID NO: 1237 and a light chain (LC) amino acid sequence of SEQ ID NO: 1126.6. The antibody or antigen-binding fragment of claim 1 , which comprises two HCs and two LCs claim 1 , wherein both HCs comprise an amino ...

Moléculas de unión para bcma y cd3

La presente invención se refiere a una molécula de unión que es al menos biespecífica, que comprende un primer y un segundo dominio de unión, en donde el primer dominio de unión es capaz de unirse al clúster de epítopes 3 de BCMA, y el segundo dominio de unión es capaz de unirse al complejo del receptor CD3 de células T. Más aún, la invención provee una secuencia de ácido nucleico que codifica la molécula de unión, un vector que comprende dicha secuencia de ácido nucleico y una célula hospedadora transformada o transfectada con dicho vector. Adicionalmente, la invención provee un proceso para la producción de la molécula de unión de la invención, un uso médico de dicha molécula de unión y un kit que comprende dicha molécula de unión.

Bispecific binding molecules for 5t4 and cd3

The present invention provides a bispecific binding molecule comprising a first and a second binding domain wherein the first binding domain is capable of binding to the epitope cluster 4 of T4 and the second binding domain is capable of binding to the CD3 receptor complex on T cells. Moreover, the invention providesa nucleic acid sequence encoding the bispecific binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention providesa process for the production of the bispecific binding molecule of the invention, a medical use of said bispecific binding molecule and a kit comprising said bispecific binding molecule.

Binding molecules for e3 of bcma and cd3

本發明係有關於一種結合分子，其至少具有雙特異性及包含一個第一結合域與一個第二結合域，其中第一結合域可與BCMA的第3簇抗原決定位結合，而第二結合域可與T細胞CD3受體複合體結合。此外，本發明提供編碼該結合分子之一核酸序列、包含該核酸序列之一載體及經該載體轉形或轉染之一宿主細胞。而且，本發明提供用於生產本發明的結合分子之一種方法、該結合分子的醫療用途及包含該結合分子之一套組。

UNION MOLECULES FOR BCMA AND CD3

Una molécula de unión, que comprende un primer y un segundo dominio de unión, en donde el primer dominio de unión es capaz de unirse a clústeres de epítopes de BCMA (antígeno de maduración de células B, TNFRSF17, CD269), y el segundo dominio de unión es capaz de unirse al complejo de receptores CD3 de células T. Más aún, una secuencia de ácido nucleico que codifica la molécula de unión, un vector que comprende dicha secuencia de ácido nucleico y una célula hospedadora transformada o transfectada con dicho vector. Adicionalmente, un procedimiento para la producción de la molécula de unión de la presente, un uso médico de dicha molécula de unión y un kit que comprende dicha molécula de unión. Composición farmacéutica. A binding molecule, comprising a first and a second binding domain, wherein the first binding domain is capable of binding to clusters of BCMA epitopes (B-cell maturation antigen, TNFRSF17, CD269), and the second domain Binding is capable of binding to the T-cell CD3 receptor complex. Moreover, a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Additionally, a process for the production of the binding molecule herein, a medical use of said binding molecule and a kit comprising said binding molecule. Pharmaceutical composition

ANTIBODY CONSTRUCTS FOR CDH19 AND CD3

La presente proporciona un constructo de anticuerpo biespecífico que comprende un primer dominio de ligación humano que se liga al CDH19 (proteína transmembrana de caderina tipo II) humano sobre la superficie de una célula objetivo y un segundo dominio de ligación que se liga a la CD3 (antígeno CD3) humana sobre la superficie de una célula T. Por otra parte proporciona un polinucleótido que codifica el constructo de anticuerpo, un vector que comprende el polinucleótido y una célula hospedera transformada o transfectada con el polinucleótido o vector. Adicionalmente, proporciona un proceso para la producción del constructo de anticuerpo, un uso médico del constructo de anticuerpo y un kit que comprende el constructo de anticuerpo. Composición farmacéutica.

Specific bispecific single stranded antibody constructs of optimized cross species

Un constructor de anticuerpo monocatenario biespecífico que se une a un antígeno de superficie de una célula diana a través de un primer dominio de unión y al antígeno de superficie de una célula T CD3 a través de un segundo dominio de unión, en el que: - el segundo dominio de unión se une a un epítope de la cadena CD3ε humana y de Callithrix jacchus, Saguinus oedipus o Saimiri sciureus, comprendiendo el epítope al menos la secuencia de aminoácidos Gln-Asp-Gly-Asn-Glu (SEQ ID NO: 1), y - una albúmina sérica está fusionada al extremo C-terminal del constructor; el constructor de anticuerpo monocatenario biespecífico no tiene una secuencia de aminoácidos tal como se representa en las SEQ ID NO: 2 y 3, y el constructor de anticuerpo monocatenario biespecífico no tiene la secuencia de aminoácidos: A bispecific single-chain antibody construct that binds to a target cell surface antigen through a first binding domain and to a CD3 T cell surface antigen through a second binding domain, wherein: the second binding domain binds to an epitope of the human CD3ε chain and of Callithrix jacchus, Saguinus oedipus or Saimiri sciureus, the epitope comprising at least the amino acid sequence Gln-Asp-Gly-Asn-Glu (SEQ ID NO: 1 ), and - a serum albumin is fused to the C-terminus of the constructor; the bispecific single-chain antibody constructor does not have an amino acid sequence as represented in SEQ ID NO: 2 and 3, and the bispecific single-chain antibody constructor does not have the amino acid sequence:

Psma and cd3 bispecific t cell engaging antibody constructs.

La presente invención provee constructos de anticuerpo biespecíficos de una modalidad específica Fc caracterizados porque comprenden un primer dominio que se une a PSMA, un segundo dominio que se une a un epítope extracelular de la cadena CD3? de humano y de Macaca y un tercer dominio, el cual es la modalidad específica Fc. Más aún, la invención provee un polinucleótido, que codifica el constructo de anticuerpo, un vector que comprende este polinucleótido, células hospedadoras, que expresan el constructo y una composición farmacéutica que comprende el mismo.

BCMA and CD3 bispecific T cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

CONSTRUCTION OF BIESPECFIC ANTIBODY DIRECTED TO MUC17 AND CD3

Construcciones de anticuerpos biespecíficos que comprenden un primer dominio que se une a MUC17, un segundo dominio que se une a un epitope extracelular de la cadena CD3e de humano y de Macaca y opcionalmente un tercer dominio, que es una Fc específica. Además, la invención provee un polinucleótido, que codifica la construcción de anticuerpo, un vector que comprende a dicho polinucleótido, células huésped que expresan la construcción y una composición farmacéutica que lo comprende.

Antibody constructs for CLDN18.2 and CD3

The present invention relates to an antibody construct comprising a domain which binds to Claudin 18.2 (CLDN18.2) and another domain which binds to CD3. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for producing the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Mageb2 binding constructs

The present disclosure relates to antibody constructs comprising a domain which binds to a MAGEB2 peptide complexed with an HLA and optionally, another domain which binds to CD3. Moreover, the disclosure provides polynucleotides encoding the antibody constructs vectors comprising said polynucleotides and host cells transformed or transfected with said polynucleotides or vectors. Furthermore, the disclosure provides processes for producing the antibody constructs of the disclosure, medical uses of said antibody constructs, and kits comprising said antibody constructs.

Polypeptide constructs selectively binding to cldn6 and cd3

The present invention relates to a polypeptide or a polypeptide construct comprising a domain which binds to Claudin 6 (CLDN6) and another domain which binds to CD3. Moreover, the invention provides a polynucleotide encoding the construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for producing the construct of the invention, a medical use of said construct and a kit comprising said construct.

BSPECIFIC ANTIGEN-BINDING MOLECULES WITH MULTIPLE TARGETS OF ENHANCED SELECTIVITY

La presente invención proporciona moléculas de unión a antígeno biespecíficas con múltiples dianas caracterizadas por comprender una primera y una segunda entidad biespecífica, comprendiendo cada una de las cuales un dominio que se une a la diana, y un segundo dominio que se une a un epítopo extracelular de la cadena CD3e humana y de Macaca, en donde ambas entidades biespecíficas están unidas entre sí por un espaciador que separa la primera y la segunda entidad biespecífica. Además, la invención proporciona un polinucleótido que codifica la molécula de unión a antígeno biespecífica con múltiples dianas, un vector que comprende este.

Antibody constructs for CDH19 and CD3

The present invention provides to antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for FLT3 and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human FLT3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for cdh19 and cd3

The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for influenza m2 and cd3

The present invention relates to an antibody construct comprising a first human binding domain specific for the extracellular part of the influenza envelope protein M2 (M2e) and a second domain specific for CD3. Moreover, the invention provides a nucleic acid molecule encoding the antibody construct, a vector comprising said nucleic acid molecule and a host cell transformed or transfected with said nucleic acid molecule or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a pharmaceutical composition comprising said antibody construct, a medical use / method of treatment relating to said antibody construct, and a kit comprising said antibody construct.

Optimized cross-species specific bispecific single chain antibody constructs

The present invention provides to a bispecific single chain antibody construct binding to a target cell surface antigen via a first binding domain and to the T cell surface antigen CD3 via a second binding domain, wherein serum albumin is fused to the C-terminus of the antibody construct. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for cdh19 and cd3

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody constructs for cdh3 and cd3

The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transiected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody constructs binding mesothelin and cd3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human MSLN on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for flt3 and cd3

The present disclosure relates to a bispecific antibody construct comprising a first binding domain which binds to human FLT3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the disclosure provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the disclosure provides a process for the production of the antibody construct of the disclosure, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody constructs binding egfrviii and cd3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody constructs binding dll3 and cd3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a Tcell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for cd70 and cd3

The present disclosure relates to a bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the disclosure provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the disclosure provides a process for the production of the antibody construct of the disclosure, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody construct directed to muc17 and cd3

The present invention provides bispecific antibody constructs characterized by comprising a first domain binding to MUC17, a second domain binding to an extracellular epitope of the human and the Macaca CD3ε chain and optionally a third domain, which is a specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Polypeptide constructs binding to cd3

The invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3s chain comprising or consisting of a VH region and a VL region, wherein i) the VH region comprises: a CDR- H1 sequence of X 1 YAX 2 N, where X1 is K, V, S, G, R, T, or I; and X 2 is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX 1 VKX 2 , where Χ 1 is S or Q; and X 2 is D, G, K, S, or E; and a CDR-H3 sequence of HX 1 NFGNSYX 2 SX 3 X 4 AY, where Χ Ί is G, R, or A; X 2 is I, L, V, or T; X 3 is Y, W or F; and X 4 is W, F or Y; and ii) wherein the VL region comprises: a CDR-L1 sequence of Χ Ί SSTGAVTX 2 X 3 X 4 YX 5 N, where Χ Ί is G, R, or A; X 2 is S or T; X 3 is G or S; X 4 is N or Y; and X 5 is P or A; a CDR-L2 sequence of X 1 TX 2 X 3 X 4 X 5 X 6 ; where Χ 1 is G or A; X 2 is K, D, or N; X 3 is F, M or K; X 4 is L or R; X 5 is A, P, or V; and X 6 is P or S; and a CDR-L3 sequence of X 1 LWYSNX 2 VW, where X 1 is V, A, or T; and X 2 is R or L; and iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X 2 4V and X 2 4F in CDR-H1; D15, and X 1 16A in CDR-H2; H1, X 1 2E, F4, and N6 in CDR-H3; and X 1 1L and W3 in CDR-L3. The invention also relates to a polynucleotide encoding the polypeptide or polypeptide construct of the invention, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or with said vector. Moreover, the invention also provides for a process for the production of said polypeptide or polypeptide construct and a pharmaceutical composition comprising said polypeptide or polypeptide construct of the invention. Furthermore, the invention relates to medical uses of said polypeptide or polypeptide construct and kits comprising said polypeptide or polypeptide construct.

Multitargeting bispecific antigen-binding molecules of increased selectivity

The present invention provides multitargeting bispecific antigen-binding molecules characterized by comprising a first and a second bispecific entity each comprising a domain binding to target, a second domain binding to an extracellular epitope of the human and the Macaca CD3ε chain, wherein both bispecific entities are linked to each other by a spacer which spaces apart the first and the second bispecific entity. Moreover, the invention provides a polynucleotide, encoding the multitargeting bispecific antigen-binding molecule, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Bcma and cd3 bispecific t cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Bispecific antibody constructs binding egfrviii and cd3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific antibody constructs binding dll3 and cd3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

BCMA and CD3 bispecific T cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Antibody constructs for EGFRVIII and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for cldn18.2 and cd3

The present invention relates to an antibody construct comprising a domain which binds to Claudin 18.2 (CLDN18.2) and another domain which binds to CD3. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for producing the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for cdh19 and cd3

The present invention provides to an antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

PSMA and CD3 bispecific T cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to PSMA, a second domain binding to an extracellular epitope of the human and the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Bispecific antibody constructs for CDH3 and CD3

The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Bispecific T cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to a target cell surface antigen, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Method for treating glioblastoma or glioma with antibody constructs for EGFRVIII and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

BCMA and CD3 bispecific T cell engaging antibody constructs

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to BCMA, a second domain binding to an extracellular epitope of the human and/or the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Process for preparing anti-human antigen receptor, anti-human antigen receptor per se, VH and VL chain, kit for the selection of anti-human antigen receptors and pharmaceutical composition containing such a receptor

The present invention relates to a process for preparing anti-human antigen receptor, wherein the process is characterized in that comprises steps of b) selecting a combination of functionally rearranged VH and VL immunoglobulin chains wherein at least said VH chain is derived from essentially unprimed mature human B-lymphocytes and said VL chain is derived from a naturally occurring human B cell repertoire, said chains being expressed from a recombinant vector and c) using an in vitro display system for binding to a human target antigen whereby prior the selection step b), there is carried out a) selection of ether said VH chain or said chain for binding to said antigen along with a chain V of another antigen receptor being specific for said target antigen. Furthermore, the invention also relates to the anti-human antigen receptor, the VH and VL immunoglobulin chains, a kit for the selection of anti-human antigen receptors as well as a pharmaceutical composition containing such a receptor.

Antibody constructs for DLL3 and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Antibody constructs for DLL3 and CD3

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising the polynucleotide and a host cell transformed or transfected with the polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of the antibody construct and a kit comprising the antibody construct.