CD38 antibody

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a PROTEASE polypeptide, or fragment thereof, and measuring a compound-PROTEASE property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including cleaved protease substrate and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of PROTEASE expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer's disease.

ANTI-CD25 ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer. 146.-. (canceled)47. A composition comprising an antibody or antigen-binding fragment thereof comprising:a) aCD25-a-686-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3;b) a variable heavy chain complementarity determining region 1 (HCDR1) selected from the group consisting of GTFSSLAIT (SEQ ID NO: 10), GTFSSLAIS (SEQ ID NO: 2), GTFSALAIS (SEQ ID NO: 11) and GTFSSLAIF (SEQ ID NO: 12);c) a variable heavy chain complementarity determining region 2 (HCDR2) selected from the group consisting of AIIPVFGTASYAQKFQG (SEQ ID NO: 13), GIIPIFGDASYAQKFQG (SEQ ID NO: 14), GIIPIFGDANYAQKLQG (SEQ ID NO: 15), GIIPLFGRANYAQKFQG (SEQ ID NO: 16) and GIIPVFGQANYAQKFQG (SEQ ID NO: 17);d) aCD25-a-686-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;e) aCD25-a-686-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andf) aCD25-a-686-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3; anda pharmaceutically acceptable carrier or excipient.48. The composition of claim 47 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain sequence having at least 95% sequence identity to the variable heavy chain region sequence selected from aCD25-a-686-m1-HCDR123 amino acid sequence (SEQ ID NO: 18) claim 47 , aCD25-a-686-m2-HCDR123 amino acid sequence (SEQ ID NO: 19) claim 47 , aCD25-a-686-m3-HCDR123 amino acid sequence (SEQ ID NO: 20) claim 47 ...

FC-OPTIMIZED ANTI-CD25 FOR TUMOR SPECIFIC CELL DEPLETION

The present disclosure relates to use of an anti-CD25 antibody, not inhibiting IL-2-CD25 interaction, with enhanced binding to activating Fc gamma Rs that lead to effective depletion of tumor-infiltrating Treg cells and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies further improves tumor rejection. 1. A method of treating a human subject who has cancer comprising the step of administering an anti-CD25 antibody to a subject , wherein said subject has a solid tumour , wherein said antibody does not inhibit the binding of Interleukin-2 (IL-2) to CD25.2. The method according to wherein the anti-CD25 antibody competes with the antibody 7G7B6 for binding to human CD25; and/or competes with the antibody MA251 for binding to human CD25.3. The method according to or wherein the anti-CD25 antibody binds to the same epitope recognised by antibody 7G7B6 and/or the epitope recognised by antibody MA251.4. The method according to any one of to wherein the anti-CD25 antibody specifically binds to an epitope of human CD25 wherein the epitope comprises one or more amino acid residues comprised in one or more of the amino acid stretches selected from amino acids 150-163 of SEQ ID NO:1 (YQCVQGYRALHRGP) claim 1 , amino acids 166-186 of SEQ ID NO:1 (SVCKMTHGKTRWTQPQLICTG) claim 1 , amino acids 42-56 of SEQ ID NO:1 (KEGTMLNCECKRGFR) and amino acids 70-88 of SEQ ID NO:1 (NSSHSSWDNQCQCTSSATR).5. The method according to wherein the anti-CD25 antibody specifically binds to an epitope of human CD25 wherein the epitope comprises at least one sequence selected from: amino acids 150-158 of SEQ ID NO:1 (YQCVQGYRA) claim 4 , amino acids 176-180 of SEQ ID NO:1 (RWTQP) claim 4 , amino acids 42-56 of SEQ ID NO:1 (KEGTMLNCECKRGFR) and amino acids 74-84 of SEQ ID NO:1 (SSWDNQCQCTS).6. The method according to wherein the anti-CD25 antibody specifically binds to an epitope of human CD25 wherein the epitope comprises at least one sequence selected ...

Anti-CD25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-672 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: PHATFKAMA YKEGTM (42-56) and YQCVQGYRALH (150-160) on CD25. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

CD38 MODULATING ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

ANTI-CD25 ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer. 146.-. (canceled)47. A composition comprising an antibody or antigen-binding fragment thereof , comprising:a) aCD25-a-646-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3;b) a variable heavy chain complementarity determining region 1 (HCDR1) selected from the group consisting of FTFASYGMH (SEQ ID NO: 10) and FTFPSYGMH (SEQ ID NO: 11);c) a a variable heavy chain complementarity determining region 2 (HCDR2) selected from the group consisting of VIWYDASTKYYADSVKG (SEQ ID NO: 12), VIWYDAINKYYADSVKG (SEQ ID NO: 13), VIWYDAVNKYYADSVKG (SEQ ID NO: 14), and VIWYDALNKYYADSVKG (SEQ ID NO: 15);d) aCD25-a-646-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;e) aCD25-a-646-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andf) aCD25-a-646-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3; anda pharmaceutically acceptable carrier or excipient.48. The composition of claim 47 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising a sequence having at least 95% sequence identity to a variable heavy chain region sequence selected from aCD25-a-646-m1-HCDR123 amino acid sequence (SEQ ID NO: 16) claim 47 , aCD25-a-646-m2-HCDR123 amino acid sequence (SEQ ID NO: 17) claim 47 , aCD25-a-646-m3-HCDR123 amino acid sequence (SEQ ID NO: 18) claim 47 , aCD25-a-646-m4-HCDR123 amino acid sequence (SEQ ID NO: 19) claim 47 , ...

MURINE CROSS-REACTIVE HUMAN CCR8 BINDERS

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is cross-reactive with murine CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general.

ANTI-CD25 FOR TUMOUR SPECIFIC CELL DEPLETION

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-634 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD25-a-634-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD25-a-634-HCDR1 amino acid sequence (SEQ ID NO: 2) as variable heavy chain complementarity determining region 1; andb) aCD25-a-634-HCDR2 amino acid sequence (SEQ ID NO: 3) as variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD25-a-634-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;b) aCD25-a-634-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andc) aCD25-a-634-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD25-a-634-HCDR123 amino acid sequence (SEQ ID NO: 5).5. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain comprising aCD25-a-634-LCDR123 amino acid sequence (SEQ ID NO: 9).6. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody claim 1 , a domain ...

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer.

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a KINASE polypeptide, or fragment thereof, and measuring a compound-KINASE property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including phosphorylated kinase substrate and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of KINASE expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer's disease.

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer.

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit aberrant amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a LIGASE polypeptide, or fragment thereof, and measuring a compound-LIGASE property related to the production of amyloid-beta peptide. Cellular assays of the method measure amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of LIGASE DNA expression agents or LIGASE agonists, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody

The present disclosure relates to use of an anti-CD25 antibody, not inhibiting IL-2-CD25 interaction, with enhanced binding to activating Fc gamma Rs that lead to effective depletion of tumor-infiltrating Treg cells and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies further improves tumor rejection.

Anti-CD25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: QCVQGYRA and RWTQPQLICTG on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer.

Nanobodies Tm Against Amyloid-Beta and Polypeptides Comprising the Same for the Treatment of Degenerative Neural Diseases Such as Alzheimer's Disease

The present invention relates to anti-A-beta polypeptides comprising at least one Nanobody, or a functional fragment thereof, directed against A-beta, for the treatment of diseases or disorders mediated by A-beta or dysfunction thereof, or mediated by amyloid plaque formation.

ANTI-CD25 FOR TUMOUR SPECIFIC CELL DEPLETION

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising a variable heavy chain region comprising an amino acid sequence of SEQ ID NO:1 , SEQ ID NO:2 or SEQ ID NO:3.2. The antibody or antigen-binding fragment thereof of any preceding claim , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain region comprising an amino acid sequence of SEQ ID NO:4 , SEQ ID NO:5 , SEQ ID NO:6 or SEQ ID NO:7.3. An antibody or antigen-binding fragment thereof , comprising a variable light chain region comprising an amino acid sequence of SEQ ID NO:4 , SEQ ID NO:5 , SEQ ID NO:6 or SEQ ID NO:7.4. The antibody or antigen-binding fragment thereof of any preceding claim , comprising:a. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 1 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 4;b. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 1 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 5;c. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 1 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 6;d. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 1 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 7;e. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 2 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 4;f. a variable ...

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in 5 pharmaceutical compositions and methods of treatment, in particular for treating cancer.

HUMAN CCR8 BINDERS

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is cross-reactive with a non-human primate CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general.

ANTI-CD25 ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising:a) aCD25-a-674-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3;b) aCD25-a-674-HCDR2 amino acid sequence (SEQ ID NO: 3) as variable heavy chain complementarity determining region 2;c) aCD25-a-674-HCDR1 amino acid sequence (SEQ ID NO: 2) as variable heavy chain complementarity determining region 1;d) aCD25-a-674-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;e) aCD25-a-674-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andf) aCD25-a-674-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3.2. (canceled)3. (canceled)4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain sequence having at least 95% sequence identity to the variable heavy chain region sequence of aCD25-a-674-HCDR123 amino acid sequence (SEQ ID NO: 5).5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain sequence having at least 95% sequence identity to the variable light chain region sequence of aCD25-a-674-LCDR123 amino acid sequence (SEQ ID NO: 9).6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody claim 1 , a domain ...

NON-BLOCKING HUMAN CCR8 BINDERS

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is a non-blocking binder of hCCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general tumour

CD38 MODULATING ANTIBODY

The present disclosure provides antibodies that bind to human CD38. In particular, the antibodies and antigen-binding portions thereof are defined by particular functional characteristics. The antibodies present features compatible for manufacturing and can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer. 1. An anti-CD38 antibody or antigen-binding fragment thereof , wherein the antibody or fragment thereof:exhibits antibody-dependent cell-mediated cytotoxicity (ADCC) activity against CD38+ target cells;exhibits no complement dependent cytotoxicity (CDC) or reduced CDC activity against a CD38+ target cell as compared to daratumumab under the same or substantially the same conditions; andinduces immune effector cell activation.2. The anti-CD38 antibody or antigen-binding fragment thereof according to wherein the antibody or fragment thereof exhibits either no CDC or exhibits CDC:a. with an EC50 that is at least 0.5-fold higher or at least 1-fold higher than daratumumab; orb. with a maximum % lysis as measured in Raji and/or Daudi cells in the presence of 10% complement that is no more than half that exhibited by daratumumab.3. The anti-CD38 antibody or antigen-binding fragment thereof according to wherein the antibody or antigen-binding fragment thereof induces CDC with an EC50 value of more than 0.05 μg/mL against Daudi cells and/or Raji cells in the presence of 10% complement.4. The anti-CD38 antibody or antigen-binding fragment thereof according to wherein the reduction in CDC activity is such that the EC50 of the antibody or antibody binding fragment thereof is at least 0.5-fold or at least 1-fold greater than that of Daratumumab under the same or substantially the same conditions.5. The anti-CD38 antibody or antigen-binding fragment thereof according to wherein reduction in CDC activity compared to daratumumab is ...

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer.

Anti-CD25 antibody agents

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer.

CD38 modulating antibody

The present disclosure provides antibodies that bind to human CD38. In particular, the antibodies and antigen-binding portions thereof are defined by particular functional characteristics. The antibodies present features compatible for manufacturing and can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

ANTI-CD25 FOR TUMOUR SPECIFIC CELL DEPLETION

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: QCVQGYRA and RWTQPQLICTG on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD25-a-674-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD25-a-674-HCDR1 amino acid sequence (SEQ ID NO: 2) as variable heavy chain complementarity determining region 1; andb) aCD25-a-674-HCDR2 amino acid sequence (SEQ ID NO: 3) as variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD25-a-674-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;b) aCD25-a-674-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andc) aCD25-a-674-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD25-a-674-HCDR123 amino acid sequence (SEQ ID NO: 5).5. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain comprising aCD25-a-674-LCDR123 amino acid sequence (SEQ ID NO: 9).6. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or ...

CD38 MODULATING ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD38-b-329-HCDR3 amino acid sequence as variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD38-b-329-HCDR1 amino acid sequence as variable heavy chain complementarity determining region 1; andb) aCD38-b-329-HCDR2 amino acid sequence as variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD38-b-329-LCDR1 amino acid sequence as variable light chain complementarity determining region 1;b) aCD38-b-329-LCDR2 amino acid sequence as variable light chain complementarity determining region 2; andc) aCD38-b-329-LCDR3 amino acid sequence as variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of claim 1 , or claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD38-b-329-HCDR123 amino acid sequence.5. The antibody or antigen-binding fragment thereof according to anyone of to claim 1 , wherein the antibody or antigen-binding fragment thereof further comprises a variable light chain comprising aCD38-b-329-LCDR123 amino acid.6. The antibody or antigen-binding fragment thereof according to any one of to claim 1 , wherein the antibody or antigen-binding fragment thereof is mutated ...

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

A-beta binding polypeptides

The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease.

ANTI-CD25 FOR TUMOUR SPECIFIC CELL DEPLETION

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-672 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: PHATFKAMA YKEGTM (42-56) and YQCVQGYRALH (150-160) on CD25. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD25-a-672-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD25-a-672-HCDR1 amino acid sequence (SEQ ID NO: 2) as variable heavy chain complementarity determining region 1; andb) aCD25-a-672-HCDR2 amino acid sequence (SEQ ID NO: 3) as variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD25-a-672-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;b) aCD25-a-672-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andc) aCD25-a-672-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD25-a-672-HCDR123 amino acid sequence (SEQ ID NO: 5).5. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain comprising aCD25-a-672-LCDR123 amino acid sequence (SEQ ID NO: 9).6. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , ...

ANTI-CD25 ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical composition and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising:a) aCD25-a-686-HCDR3 amino acid sequence (SEQ ID NO: 4) as variable heavy chain complementarity determining region 3;b) aCD25-a-686-HCDR1 amino acid sequence (SEQ ID NO: 2) as variable heavy chain complementarity determining region 1;c) aCD25-a-686-HCDR2 amino acid sequence (SEQ ID NO: 3) as variable heavy chain complementarity determining region 2;d) aCD25-a-686-LCDR1 amino acid sequence (SEQ ID NO: 6) as variable light chain complementarity determining region 1;e) aCD25-a-686-LCDR2 amino acid sequence (SEQ ID NO: 7) as variable light chain complementarity determining region 2; andf) aCD25-a-686-LCDR3 amino acid sequence (SEQ ID NO: 8) as variable light chain complementarity determining region 3.2. (canceled)3. (canceled)4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain sequence having at least 95% sequence identity to the variable heavy chain region sequence of aCD25-a-686-HCDR123 amino acid sequence (SEQ ID NO:5).5. The antibody or antigen-binding fragment thereof of a claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain sequence having at least 95% sequence identity to the variable light chain region sequence of aCD25-a-686-LCDR123 amino acid (SEQ ID NO: 9).6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody claim 1 , a domain antibody ...

Anti-CD25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: YQCVQGYRALHRGP (150 to 163) or SVCKMTHGKTRWTQP (166 to 180) on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

ANG2-BINDING MOLECULES

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same. 1. An Ang2-binding molecule comprising an immunoglobulin single variable domain , wherein said immunoglobulin single variable domain comprises three complementarity determining regions CDR1 , CDR2 and CDR3 , wherein CDR1 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 168 to 170 , CDR2 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 171 to 173 and CDR3 has an amino acid selected from amino acid sequences shown in SEQ ID NOs: 174 to 177.2. The Ang2-binding molecule according to claim 1 , wherein(a) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 174, or wherein(b) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 175, or wherein(c) CDR1 has an amino acid sequence shown in SEQ ID NO: 169, CDR2 has an amino acid sequence shown in SEQ ID NO: 172 and CDR3 has an amino acid sequence shown in SEQ ID NO: 176, or wherein(d) CDR1 has an amino acid sequence shown in SEQ ID NO: 170, CDR2 has an amino acid sequence shown in SEQ ID NO: 173 and CDR3 has an amino acid sequence shown in SEQ ID NO: 177.3. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH or a domain antibody.4. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH.5. The Ang2-binding molecule according to claim 4 , wherein said VHH consists of an ...

ANTI-CD25 FOR TUMOUR SPECIFIC CELL DEPLETION

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: YQCVQGYRALHRGP (150 to 163) or SVCKMTHGKTRWTQP (166 to 180) on CD25 Antibodies and antigen-binding portions N thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

and VEGF-binding molecules

ANG2-BINDING MOLECULES

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same. 1. An Ang2-binding molecule comprising an immunoglobulin single variable domain , wherein said immunoglobulin single variable domain comprises three complementarity determining regions CDR1 , CDR2 and CDR3 , wherein CDR1 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 168 to 170 , CDR2 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 171 to 173 and CDR3 has an amino acid selected from amino acid sequences shown in SEQ ID NOs: 174 to 177.2. The Ang2-binding molecule according to claim 1 , wherein(a) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 174, or wherein(b) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 175, or wherein(c) CDR1 has an amino acid sequence shown in SEQ ID NO: 169, CDR2 has an amino acid sequence shown in SEQ ID NO: 172 and CDR3 has an amino acid sequence shown in SEQ ID NO: 176, or wherein(d) CDR1 has an amino acid sequence shown in SEQ ID NO: 170, CDR2 has an amino acid sequence shown in SEQ ID NO: 173 and CDR3 has an amino acid sequence shown in SEQ ID NO: 177.3. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH or a domain antibody.4. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH.5. The Ang2-binding molecule according to claim 4 , wherein said VHH consists of an ...

ANTI-CD25 ANTIBODY AGENTS

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in 5 pharmaceutical compositions and methods of treatment, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:11 as variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 9 as a variable heavy chain complementarity determining region 1; andb) the amino acid sequence for SEQ ID NO:2 or SEQ ID NO: 10 as a variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 12 as a variable light chain complementarity determining region 1;b) the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 13 as a variable light chain complementarity determining region 2; andc) the amino acid sequence of SEQ ID NO:6 or SEQ ID NO:14 as variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:7.5. The antibody or antigen-binding fragment thereof of any preceding claim claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable light chain region comprising the amino acid sequence of SEQ ID NO: 8.6. The antibody or antigen-binding fragment thereof of any one of to claim 1 , wherein the antibody or antigen-binding fragment thereof ...

Anti-CD25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-634 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Anti-CD25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

CD38 modulating antibody

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

AN LTBR AGONIST IN COMBINATION THERAPY AGAINST CANCER

The present invention relates to a combination comprising a Treg depletor and an LTBR agonist. Such a combination is particularly useful for use in the treatment of a cancer.

Methods, compositions and compound assays for inhibiting amyloid-beta protein production

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a SPHK polypeptide, or fragment thereof, and measuring a compound-SPHK property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including phosphorylated kinase substrate and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of SPHK expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer's Disease.

VEGF-BINDING MOLECULES

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same. 1. VEGF-binding molecule comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 , CDR2 and CDR3 , respectively , wherein said CDR3 has the amino acid sequence Ser Arg Ala Tyr Xaa Ser Xaa Arg Leu Arg Leu Xaa Xaa Thr Tyr Xaa Tyr as shown in SEQ ID NO: 1 , whereinXaa at position 5 is Gly or Ala;Xaa at position 7 is Ser or Gly;Xaa at position 12 is Gly, Ala or Pro;Xaa at position 13 is Asp or Gly;Xaa at position 16 is Asp or Glu; andwherein said VEGF-binding molecule is capable of blocking the interaction of human recombinant VEGF165 with the human recombinant VEGFR-2 with an inhibition rate of ≧60%.3. A VEGF-binding molecule of claim 2 , which comprises one or more immunoglobulin single variable domains each containinga) a CDR3 with an amino acid sequence selected from a first group of sequences shown in SEQ ID NO: 2 to 8;b) a CDR1 and a CDR2 with an amino acid sequences that is contained, as indicated in Table 3, in a sequence selected from a second group of sequences shown in SEQ ID NOs: 9 to 46, wherein said second sequence contains the respective CDR3 in said selected sequence according to a).4. A VEGF-binding molecule of claim 3 , wherein said one or more immunoglobulin single variable domains are VHHs.5. A VEGF-binding molecule of claim 4 , wherein said one or more VHHs have amino acid sequences selected from the amino acid sequences shown in SEQ ID NOs: 9-46.6. A VEGF-binding molecule of claim 5 , which comprises one or more VHHs having amino acid sequences selected from SEQ ID NO: 15 claim 5 , SEQ ID NO: 18 and SEQ ID NO: 25.7. A VEGF-binding ...

A-BETA BINDING POLYPEPTIDES

The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease. 115-. (canceled)17. An expression vector comprising a nucleic acid molecule according to .1920-. (canceled)22. The method of claim 21 , wherein said disease claim 21 , disorder or condition is selected from the group consisting of neurodegenerative diseases or disorders claim 21 , Alzheimer's disease claim 21 , dementia of the Alzheimer type claim 21 , dry AMD claim 21 , glaucoma claim 21 , cerebral amyloid angiopathy claim 21 , trisomy 21 (Down's Syndrome) claim 21 , adult Down syndrome claim 21 , hereditary cerebral hemorrhage with amyloidosis of the Dutch-type (HCHWA-D) claim 21 , dementia with Lewy Bodies claim 21 , frontotemporal lobar degeneration claim 21 , glaucoma claim 21 , amyotrophic lateral sclerosis claim 21 , sporadic inclusion body myositis claim 21 , and anxiety disorder in an elderly human subject.23. (canceled)25. The method of claim 21 , further comprising administering an additional therapeutic agent selected from the group consisting of ELND-005 claim 21 , Caprospinol claim 21 , NRM-8499 claim 21 , PBT-2 claim 21 , Posiphen claim 21 , EHT-0202 claim 21 , CTS-21166 claim 21 , Semagacest claim 21 , BMS-708163 claim 21 , BMS-299897 claim 21 , BMS-433796 claim 21 , ELND-006 claim 21 , ELN-475516 claim 21 , ELN-318463 claim 21 , ELN-475513 claim 21 , Begacestat claim 21 , E-2012 claim 21 , CHF-5074 claim 21 , Dimebolin claim 21 , and PF-4494700.26. (canceled)2831-. (canceled) The present invention relates to novel beta-amyloid peptide (in the following: “A-beta”) binding polypeptides, the polypeptides comprising specific ...

AMINO ACID SEQUENCES DIRECTED AGAINST GPCRS AND POLYPEPTIDES COMPRISING THE SAME FOR THE TREATMENT OF GPCR-RELATED DISEASES AND DISORDERS

The present invention relates to amino acid sequences that are directed against G-protein coupled receptors (GPCRs), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes. 1. A polypeptide comprising two or more amino acid sequences which are directed against GPCRs , whereina) at least one “first” amino acid sequence is directed against a first antigenic determinant, epitope, part, domain, subunit or conformation of a GPCR; and wherein,b) at least one “second” amino acid sequence is directed against a second antigenic determinant, epitope, part, domain, subunit or conformation of said GPCR different from the first antigenic determinant epitope, part, domain, subunit or conformation, respectively.2. The polypeptide according to claim 1 , wherein said at least one “first” amino acid sequence and/or said at least one “second” amino acid sequence consists of a domain antibody claim 1 , an amino acid sequence that is suitable for use as a domain antibody claim 1 , a single domain antibody claim 1 , an amino acid sequence that is suitable for use as a single domain antibody claim 1 , a “dAb” claim 1 , an amino acid sequence that is suitable for use as a dAb claim 1 , a Nanobody or a VHH sequence.3. The polypeptide according to claim 1 , wherein said at least one “first” amino acid sequence and/or said ...

ANG2-BINDING MOLECULES

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same. 1. An Ang2-binding molecule comprising an immunoglobulin single variable domain , wherein said immunoglobulin single variable domain comprises three complementarity determining regions CDR1 , CDR2 and CDR3 , wherein CDR1 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 168 to 170 , CDR2 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 171 to 173 and CDR3 has an amino acid selected from amino acid sequences shown in SEQ ID NOs: 174 to 177.2. The Ang2-binding molecule according to claim 1 , wherein(a) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 174, or wherein(b) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 175, or wherein(c) CDR1 has an amino acid sequence shown in SEQ ID NO: 169, CDR2 has an amino acid sequence shown in SEQ ID NO: 172 and CDR3 has an amino acid sequence shown in SEQ ID NO: 176, or wherein(d) CDR1 has an amino acid sequence shown in SEQ ID NO: 170, CDR2 has an amino acid sequence shown in SEQ ID NO: 173 and CDR3 has an amino acid sequence shown in SEQ ID NO: 177.3. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is aVHH or a domain antibody.4. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH.5. The Ang2-binding molecule according to claim 4 , wherein said VHH consists of an ...

A-BETA BINDING POLYPEPTIDES

The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease. 120-. (canceled)21. A method of using a polypeptide for the treatment , prevention or alleviation of a disease , disorder or condition in a human being , wherein said polypeptide comprises a first immunoglobulin single variable domain and a second immunoglobulin single variable domain , wherein the CDR sequences of said first immunoglobulin variable domain (CDR(1) sequences) and the CDR sequences of said second immunoglobulin variable domain (CDR(2) sequences) are defined as follows:CDR(1)1: SEQ ID NO:17CDR(1)2: SEQ ID NO:18CDR(1)3: SEQ ID NO:19CDR(2)1: SEQ ID NO:14CDR(2)2: SEQ ID NO:15CDR(2)3: SEQ ID NO:16,orCDR(1)1: SEQ ID NO:14CDR(1)2: SEQ ID NO:15CDR(1)3: SEQ ID NO:16CDR(2)1: SEQ ID NO:17CDR(2)2: SEQ ID NO:18CDR(2)3: SEQ ID NO:19.22. The method of claim 21 , wherein said disease claim 21 , disorder or condition is selected from the group consisting of neurodegenerative diseases or disorders claim 21 , Alzheimer's disease claim 21 , dementia of the Alzheimer type claim 21 , dry age-related macular degeneration (AMD) claim 21 , glaucoma claim 21 , cerebral amyloid angiopathy claim 21 , trisomy 21 (Down's Syndrome) claim 21 , adult Down syndrome claim 21 , hereditary cerebral hemorrhage with amyloidosis of the Dutch-type (HCHWA-D) claim 21 , dementia with Lewy Bodies claim 21 , frontotemporal lobar degeneration claim 21 , glaucoma claim 21 , amyotrophic lateral sclerosis claim 21 , sporadic inclusion body myositis claim 21 , and anxiety disorder in an elderly human subject.23. (canceled)24. A method for preventing and/or treating a ...

BISPECIFIC BINDING MOLECULES FOR ANTI-ANGIOGENESIS THERAPY

Bispecific binding molecules, in particular immunoglobulin single variable domains such as VHHs and domain antibodies, comprising a VEGF-binding component and a DII4-binding component in one molecule. Pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- and DII4-mediated effects on angiogenesis. Nucleic acids encoding the bispecific binding molecules, host cells and methods for preparing same. 1. A bispecific binding molecule comprising a DII4-binding component and a VEGF-binding component.2. A bispecific binding molecule of claim 1 , wherein said DII4-binding component and said VEGF-binding component comprise at least one DII4-binding immunoglobulin single variable domain and at least one VEGF-binding immunoglobulin single variable domain claim 1 , respectively.3. A bispecific binding molecule of claim 2 , wherein said immunoglobulin single variable domains are VHHs.4. A bispecific binding molecule of claim 2 , wherein said VEGF-binding component is located N-terminally.5. A bispecific binding molecule of claim 2 , wherein said DII4-binding component and said VEGF-binding component comprise at least one VEGF-binding immunoglobulin single variable domain and at least one DII4-binding immunoglobulin single variable domain claim 2 , respectively claim 2 , wherein each of said immunoglobulin single variable domains has four framework regions and three complementarity determining regions CDR1 claim 2 , CDR2 and CDR3 claim 2 , respectively claim 2 , wherein [ Xaa at position 8 is Arg, Ala or Glu;', 'Xaa at position 11 is Leu or Glu; and', 'Xaa at position 14 is Tyr or His; and, 'i. Arg Ala Pro Asp Thr Arg Leu Xaa Pro Tyr Xaa Tyr Asp Xaa as shown in SEQ ID NO: 1, wherein'}, 'Xaa is Gln, Ala or Tyr; and wherein', 'ii. Asp Arg Tyr Ile Trp Ala Arg Gln Gly Glu Tyr Trp Gly Ala Tyr Xaa Asp Tyr as shown in SEQ ID NO: 2, wherein'}], 'a) a CDR3 of said at least one DII4-binding immunoglobulin single variable domain ...

CD38 ANTIBODY

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

BIOLOGICAL MATERIALS RELATED TO CXCR7

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth. 1. A construct comprising at least one immunoglobulin single variable domain (ISVD) that binds to and/or recognizes amino acid residue M33 , and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1) and at least one ISVD that binds to and/or recognizes amino acid residue WF19 , and optionally S23 and/or D25 of CXCR7 (SEQ ID NO: 1).2. The construct according to for use as a medicament to reduce tumour growth and/or to treat cancer claim 1 , preferably head and neck cancer or GBM.3. An immunoglobulin single variable domain that can specifically displace SDF-1 and I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 and I-TAC displacement of 50% or more.4. An immunoglobulin single variable domain that can specifically displace SDF-1 on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 displacement of 50% or more.5. An immunoglobulin single variable domain that can specifically displace I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average I-TAC displacement of 50% or more.6. The immunoglobulin single variable domain of claim 3 , wherein the average Ki is 50 nM or less.7. The immunoglobulin single variable domain of claim 3 , wherein the average Ki is 10 nM or less.8. The immunoglobulin single variable domain of claim 3 , wherein the average SDF-1 or I-TAC displacement is 80% or more.9. An immunoglobulin single variable domain that can bind ...

BIOLOGICAL MATERIALS RELATED TO CXCR7

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. 1. An immunoglobulin single variable domain that can specifically displace SDF-1 and I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 and I-TAC displacement of 50% or more.2. An immunoglobulin single variable domain that can specifically displace SDF-1 on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 displacement of 50% or more.3. An immunoglobulin single variable domain that can specifically displace I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average I-TAC displacement of 50% or more.4. The immunoglobulin single variable domain of claim 1 , wherein the average Ki is 50 nM or less.5. The immunoglobulin single variable domain of claim 1 , wherein the average Ki is 10 nM or less.6. The immunoglobulin single variable domain of claim 1 , wherein the average SDF-1 or I-TAC displacement is 80% or more.7. (canceled)8. The immunoglobulin single variable domain of claim 1 , wherein the immunoglobulin single variable domain comprises an amino acid sequence with the formula 1{'br': None, 'FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\u2003\u2003(1);'}wherein FR1 to FR4 refer to framework regions 1 to 4 and are framework regions of an immunoglobulin single variable domain; a) SEQ ID NO: 10,', 'b) amino acid sequences that have at least 80% amino acid identity with SEQ ID NO: 10,', 'c) amino acid sequences that have 3, 2, or 1 amino acid difference with SEQ ID NO: 10,, 'and wherein CDR1 is chosen from the group consisting of d) SEQ ID NO: 20;', 'e) amino acid sequences that have at least 80% amino acid identity ...

ANG2-BINDING MOLECULES

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same. 1. An Ang2-binding molecule comprising an immunoglobulin single variable domain , wherein said immunoglobulin single variable domain comprises three complementarity determining regions CDR1 , CDR2 and CDR3 , wherein CDR1 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 168 to 170 , CDR2 has an amino acid sequence selected from amino acid sequences shown in SEQ ID Nos: 171 to 173 and CDR3 has an amino acid selected from amino acid sequences shown in SEQ ID NOs: 174 to 177.2. The Ang2-binding molecule according to claim 1 , wherein(a) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 174, or wherein(b) CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 175, or wherein(c) CDR1 has an amino acid sequence shown in SEQ ID NO: 169, CDR2 has an amino acid sequence shown in SEQ ID NO: 172 and CDR3 has an amino acid sequence shown in SEQ ID NO: 176, or wherein(d) CDR1 has an amino acid sequence shown in SEQ ID NO: 170, CDR2 has an amino acid sequence shown in SEQ ID NO: 173 and CDR3 has an amino acid sequence shown in SEQ ID NO: 177.3. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is aVHH or a domain antibody.4. The Ang2-binding molecule according to claim 1 , wherein said immunoglobulin single variable domain is a VHH.5. The Ang2-binding molecule according to claim 4 , wherein said VHH consists of an ...

BISPECIFIC ANTI-CXCR7 IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth. 1. A construct comprising at least one immunoglobulin single variable domain (ISVD) that binds to and/or recognizes amino acid residue M33 , and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1) and at least one ISVD that binds to and/or recognizes amino acid residue WF19 , and optionally S23 and/or D25 of CXCR7 (SEQ ID NO: 1).2. The construct according to for use as a medicament to reduce tumour growth and/or to treat cancer claim 1 , preferably head and neck cancer or GBM.3. An immunoglobulin single variable domain that can specifically displace SDF-1 and/or I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 and I-TAC displacement of 50% or more.48-. (canceled)9. An immunoglobulin single variable domain that can bind human CXCR7 (SEQ ID NO: 1) with a Kd of less than 50 nM.10. An immunoglobulin single variable domain selected from the group consisting ofimmunoglobulin single variable domains that bind to and/or recognize amino acid residue M33, and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1); andimmunoglobulin single variable domains that bind to and/or recognize amino acid residue W19, and optionally amino acid residue S23 and/or amino acid residue D25 of CXCR7 (SEQ ID NO: 1).11. (canceled)125. The immunoglobulin single variable domain according to claim for use as a medicament to reduce tumour growth and/or to treat cancer claim 1 , preferably head and neck ...

BISPECIFIC ANTI-CXCR7 IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth. 1. A construct comprising at least one immunoglobulin single variable domain (ISVD) that binds to and/or recognizes amino acid residue M33 , and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1) and at least one ISVD that binds to and/or recognizes amino acid residue W19 , and optionally S23 and/or D25 of CXCR7 (SEQ ID NO: 1).2. The construct according to for use as a medicament to reduce tumour growth and/or to treat cancer claim 1 , preferably head and neck cancer or GBM.3. An immunoglobulin single variable domain that can specifically displace SDF-1 and/or I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and an average SDF-1 and I-TAC displacement of 50% or more.48-. (canceled)9. An immunoglobulin single variable domain that can bind human CXCR7 (SEQ ID NO: 1) with a Kd of less than 50 nM.10. An immunoglobulin single variable domain selected from the group consisting ofimmunoglobulin single variable domains that bind to and/or recognize amino acid residue M33, and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1); andimmunoglobulin single variable domains that bind to and/or recognize amino acid residue W19, and optionally amino acid residue S23 and/or amino acid residue D25 of CXCR7 (SEQ ID NO: 1).11. (canceled)125. The immunoglobulin single variable domain according to claim for use as a medicament to reduce tumour growth and/or to treat cancer claim 1 , preferably head and neck ...

VEGF-BINDING MOLECULES

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same. 1. VEGF-binding molecule comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 , CDR2 and CDR3 , respectively , wherein said CDR3 has the amino acid sequence Ser Arg Ala Tyr Xaa Ser Xaa Arg Leu Arg Leu Xaa Xaa Thr Tyr Xaa Tyr as shown in SEQ ID NO: 1 , whereinXaa at position 5 is Gly or Ala;Xaa at position 7 is Ser or Gly;Xaa at position 12 is Gly, Ala or Pro;Xaa at position 13 is Asp or Gly;Xaa at position 16 is Asp or Glu; andwherein said VEGF-binding molecule is capable of blocking the interaction of human recombinant VEGF165 with the human recombinant VEGFR-2 with an inhibition rate of ≧60%.3. A VEGF-binding molecule of claim 2 , which comprises one or more immunoglobulin single variable domains each containinga) a CDR3 with an amino acid sequence selected from a first group of sequences shown in SEQ ID NO: 2 to 8;b) a CDR1 and a CDR2 with an amino acid sequences that is contained, as indicated in Table 3, in a sequence selected from a second group of sequences shown in SEQ ID NOs: 9 to 46, wherein said second sequence contains the respective CDR3 in said selected sequence according to a).4. A VEGF-binding molecule of claim 3 , wherein said one or more immunoglobulin single variable domains are VHHs.5. A VEGF-binding molecule of claim 4 , wherein said one or more VHHs have amino acid sequences selected from the amino acid sequences shown in SEQ ID NOs: 9-46.6. A VEGF-binding molecule of claim 5 , which comprises one or more VHHs having amino acid sequences selected from SEQ ID NO: 15 claim 5 , SEQ ID NO: 18 and SEQ ID NO: 25.7. A VEGF-binding ...

VEGF-BINDING MOLECULES

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same. 1. VEGF-binding molecule comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 , CDR2 and CDR3 , respectively , wherein said CDR3 has the amino acid sequence Ser Arg Ala Tyr Xaa Ser Xaa Arg Leu Arg Leu Xaa Xaa Thr Tyr Xaa Tyr as shown in SEQ ID NO: 1 , whereinXaa at position 5 is Gly or Ala;Xaa at position 7 is Ser or Gly;Xaa at position 12 is Gly, Ala or Pro;Xaa at position 13 is Asp or Gly;Xaa at position 16 is Asp or Glu; andwherein said VEGF-binding molecule is capable of blocking the interaction of human recombinant VEGF165 with the human recombinant VEGFR-2 with an inhibition rate of ≥60%.3. A VEGF-binding molecule of claim 2 , which comprises one or more immunoglobulin single variable domains each containinga) a CDR3 with an amino acid sequence selected from a first group of sequences shown in SEQ ID NO: 2 to 8;b) a CDR1 and a CDR2 with an amino acid sequences that is contained, as indicated in Table 3, in a sequence selected from a second group of sequences shown in SEQ ID NOs: 9 to 46, wherein said second sequence contains the respective CDR3 in said selected sequence according to a).4. A VEGF-binding molecule of claim 3 , wherein said one or more immunoglobulin single variable domains are VHHs.5. A VEGF-binding molecule of claim 4 , wherein said one or more VHHs have amino acid sequences selected from the amino acid sequences shown in SEQ ID NOs: 9-46.6. A VEGF-binding molecule of claim 5 , which comprises one or more VHHs having amino acid sequences selected from SEQ ID NO: 15 claim 5 , SEQ ID NO: 18 and SEQ ID NO: 25.7. A VEGF-binding ...

Compounds and methods for tumour-specific cell depletion

Described is a human IgG2 anti-CD25 antibody, wherein the antibody depletes CD25 cells, in particular tumour-infiltrating regulatory T cells. The antibody can be used in the treatment of cancer, for example in treating solid tumours and in haematological cancers.

VEGF-BINDING MOLECULES

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same. 1. VEGF-binding molecule comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 , CDR2 and CDR3 , respectively , wherein said CDR3 has the amino acid sequence Ser Arg Ala Tyr Xaa Ser Xaa Arg Leu Arg Leu Xaa Xaa Thr Tyr Xaa Tyr as shown in SEQ ID NO: 1 , whereinXaa at position 5 is Gly or Ala;Xaa at position 7 is Ser or Gly;Xaa at position 12 is Gly, Ala or Pro;Xaa at position 13 is Asp or Gly;Xaa at position 16 is Asp or Glu; andwherein said VEGF-binding molecule is capable of blocking the interaction of human recombinant VEGF165 with the human recombinant VEGFR-2 with an inhibition rate of ≥60%.3. A VEGF-binding molecule of claim 2 , which comprises one or more immunoglobulin single variable domains each containinga) a CDR3 with an amino acid sequence selected from a first group of sequences shown in SEQ ID NO: 2 to 8;b) a CDR1 and a CDR2 with an amino acid sequences that is contained, as indicated in Table 3, in a sequence selected from a second group of sequences shown in SEQ ID NOs: 9 to 46, wherein said second sequence contains the respective CDR3 in said selected sequence according to a).4. A VEGF-binding molecule of claim 3 , wherein said one or more immunoglobulin single variable domains are VHHs.5. A VEGF-binding molecule of claim 4 , wherein said one or more VHHs have amino acid sequences selected from the amino acid sequences shown in SEQ ID NOs: 9-46.6. A VEGF-binding molecule of claim 5 , which comprises one or more VHHs having amino acid sequences selected from SEQ ID NO: 15 claim 5 , SEQ ID NO: 18 and SEQ ID NO: 25.7. A VEGF-binding ...

CD38 MODULATING ANTIBODY

The present disclosure provides antibody sequences found in antibodies that bind to human CD In particular, the present disclosure provides sequences of anti-human CD antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD38-a-323-HCDR3 amino acid sequence as a variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD38-a-323-HCDR1 amino acid sequence as a variable heavy chain complementarity determining region 1; andb) aCD38-a-323-HCDR2 amino acid sequence as a variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD38-a-323-LCDR1 amino acid sequence as a variable light chain complementarity determining region 1;b) aCD38-a-323-LCDR2 amino acid sequence as a variable light chain complementarity determining region 2; andc) aCD38-a-323-LCDR3 amino acid sequence as a variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof of any one of to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD38-a-323-HCDR123 amino acid sequence.5. The antibody or antigen-binding fragment thereof of any one of to claim 1 , wherein the antibody or antigen-binding fragment thereof further comprises a variable light chain comprising aCD38-a-323-LCDR123 amino acid sequence.6. The antibody or antigen-binding fragment thereof according to any one of to wherein the antibody or an antigen-binding fragment thereof is selected ...

CD38 ANTIBODY

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer. 1. An antibody or antigen-binding fragment thereof , comprising the aCD38-a-309-HCDR3 amino acid sequence as a variable heavy chain complementarity determining region 3.2. The antibody or antigen-binding fragment thereof of claim 1 , further comprisinga) aCD38-a-309-HCDR1 amino acid sequence as a variable heavy chain complementarity determining region 1; andb) aCD38-a-309-HCDR2 amino acid sequence as a variable heavy chain complementarity determining region 2.3. The antibody or antigen-binding fragment thereof of or claim 1 , further comprising:a) aCD38-a-309-LCDR1 amino acid sequence as a variable light chain complementarity determining region 1;b) aCD38-a-309-LCDR2 amino acid sequence as a variable light chain complementarity determining region 2; andc) aCD38-a-309-LCDR3 amino acid sequence as a variable light chain complementarity determining region 3.4. The antibody or antigen-binding fragment thereof according to any one of the preceding claims claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain comprising aCD38-a-309-HCDR123 amino acid sequence.5. The antibody or antigen-binding fragment thereof according to any one of the preceding claims claim 1 , wherein the antibody or antigen-binding fragment thereof further comprises a variable light chain comprising aCD38-a-309-LCDR123 amino acid.6. The antibody or antigen-binding fragment thereof according to any one of to wherein the ...

VEGF-BINDING MOLECULES

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same. 1. VEGF-binding molecule comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 , CDR2 and CDR3 , respectively , wherein said CDR3 has the amino acid sequence Ser Arg Ala Tyr Xaa Ser Xaa Arg Leu Arg Leu Xaa Xaa Thr Tyr Xaa Tyr as shown in SEQ ID NO: 1 , whereinXaa at position 5 is Gly or Ala;Xaa at position 7 is Ser or Gly;Xaa at position 12 is Gly, Ala or Pro;Xaa at position 13 is Asp or Gly;Xaa at position 16 is Asp or Glu; andwherein said VEGF-binding molecule is capable of blocking the interaction of human recombinant VEGF165 with the human recombinant VEGFR-2 with an inhibition rate of ≥60%.3. A VEGF-binding molecule of claim 2 , which comprises one or more immunoglobulin single variable domains each containinga) a CDR3 with an amino acid sequence selected from a first group of sequences shown in SEQ ID NO: 2 to 8;b) a CDR1 and a CDR2 with an amino acid sequences that is contained, as indicated in Table 3, in a sequence selected from a second group of sequences shown in SEQ ID NOs: 9 to 46, wherein said second sequence contains the respective CDR3 in said selected sequence according to a).4. A VEGF-binding molecule of claim 3 , wherein said one or more immunoglobulin single variable domains are VHHs.5. A VEGF-binding molecule of claim 4 , wherein said one or more VHHs have amino acid sequences selected from the amino acid sequences shown in SEQ ID NOs: 9-46.6. A VEGF-binding molecule of claim 5 , which comprises one or more VHHs having amino acid sequences selected from SEQ ID NO: 15 claim 5 , SEQ ID NO: 18 and SEQ ID NO: 25.7. A VEGF-binding ...

Dll4-binging molecules

DII4-binding molecules, preferably DII4-binding immunoglobulin single variable domains like VHHs and VHs, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with DII4-mediated effects on angiogenesis. Bispecific DII4-binding molecules that also bind to VEGF-A. Nucleic acids encoding DII4-binding molecules, host cells and methods for preparing same.

BISPECIFIC UNION MOLECULES FOR ANTI-ANGIOGENESIS THERAPY

Moléculas de unión biespecíficas, en particular dominios variables sencillos de inmunoglobulina tales como VHH y anticuerpos de dominio, que comprenden un componente de unión a VEGF y un componente de unión a DII4 en una molécula. Composiciones farmacéuticas que contienen los mismos y su uso en el tratamiento de enfermedades que están asociadas con efectos mediados por VEGF y DII4 sobre la angiogénesis. Ácidos nucleicos que codifican las moléculas de unión biespecíficas, células hospedadoras y métodos para prepararlas

Bispecific binding molecules for anti-angiogenesis therapy

Bispecific binding molecules, in particular immunoglobulin single variable domains such as VHHs and domain antibodies, comprising a VEGF-binding component and a Dll4-binding component in one molecule. Pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- and Dll4-mediated effects on angiogenesis. Nucleic acids encoding the bispecific binding molecules, host cells and methods for preparing same.

Dll4-binding molecules

DII4-binding molecules, preferably DII4-binding immunoglobulin single variable domains like VHHs and VHs, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with DII4-mediated effects on angiogenesis. Bispecific DII4-binding molecules that also bind to VEGF-A. Nucleic acids encoding DII4-binding molecules, host cells and methods for preparing same.

Biparatopic abeta binding polypeptides

The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease.

Vegf-binding molecules

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs anddomain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- mediated effects on angiogenesis.Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same.

Ang2-binding molecules

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same.

Ccr8 non-blocking binders

The present invention relates CCR8 binders having cytotoxic activity, wherein the CCR8 binder is a non-blocking binder of CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general tumour.

An ltbr agonist in combination therapy against cancer

The present invention relates to a combination comprising a Treg depletor and an LTBR agonist. Such a combination is particularly useful for use in the treatment of a cancer.

A ccr8 antagonist antibody in combination with a lymphotoxin beta receptor agonist antibody in therapy against cancer

The present invention relates combinations of a CCR8 binder having cytotoxic activity and a HEV inducer. Such combinations are particularly useful in the treatment of a cancer.

Non-blocking human ccr8 binders

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is a non-blocking binder of hCCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general tumour

Murine cross-reactive human ccr8 binders

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is cross-reactive with murine CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general.

Human ccr8 binders

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is cross-reactive with a non-human primate CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general.

Amino acid sequences directed against GPCRS and polypeptides comprising the same for the treatment of GPCR-related diseases and disorders

The present invention relates to amino acid sequences that are directed against G-protein coupled receptors (GPCRs), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.

Immunoglobulin single variable domains directed against cxcr7

Bispecific anti-CXCR7 immunoglobulin single variable domains

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth.

VEGF-binding molecules

VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same.

A-beta binding polypeptides

The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease.

Single domain camelide anti-amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenerative neural diseases such as alzheimer's disease

The present invention relates to anti-A-beta polypeptides comprising at least one Nanobody, or a functional fragment thereof, directed against A-beta, for the treatment of diseases or disorders mediated by A-beta or dysfunction thereof, or mediated by amyloid plaque formation.

Amino acid sequences directed against vascular endothelial growth factor and polypeptides comprising the same for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization

The present invention relates to amino acid sequences that are directed against vascular endothelial growth factor (VEGF), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The amino acid sequences, compounds and constructs can be used for prophylactic, therapeutic or diagnostic purposes, such as for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization.

Bispecific binding molecules for anti-angiogenesis therapy

Bispecific binding molecules, in particular immunoglobulin single variable domains such as VHHs and domain antibodies, comprising a VEGF-binding component and a Dll4-binding component in one molecule. Pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- and Dll4-mediated effects on angiogenesis. Nucleic acids encoding the bispecific binding molecules, host cells and methods for preparing same.

Ang2-binding molecules.

La presente invención se refiere a moléculas que se unen a Ang2, caracterizada porque comprende un dominio variable simple de inmunoglobulina, en donde dicho dominio variable simple de inmunoglobulina comprende tres regiones determinantes de la complementariedad CDR1, CDR2, y CDR3, en donde CDR1 tiene una secuencia de aminoácidos mostrada en SEC ID NO. 168, CDR2 tiene una secuencia de aminoácidos mostrada en SEC ID NO. 171 y CDR3 tiene una secuencia de aminoácidos mostrada en SEC ID NO. 175.

Cd38 modulating antibody

The present disclosure provides antibodies that bind to human CD38. In particular, the antibodies and antigen-binding portions thereof are defined by particular functional characteristics. The antibodies present features compatible for manufacturing and can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen- binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

Ang2-binding molecules

DLL-4 BINDING MOLECULES.

Moléculas de unión a Dll4, preferiblemente dominios variables sencillos de inmunoglobulina de unión a Dll4 tal como VHH y VH, composiciones farmacéuticas que contienen a las mismas y su uso en el tratamiento de enfermedades que están asociadas con efectos mediados por Dll4 en angiogénesis. Moléculas de unión a Dll4 biespecíficas que también se unen a VEGF-A. Ácidos nucleicos que codifican moléculas de unión a Dll4, células hospedadoras y métodos para preparar a los mismos.

Amino acid sequences directed against vascular endothelial growth factor and polypeptides comprising the same for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization

The present invention relates to amino acid sequences that are directed against vascular endothelial growth factor (VEGF), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The amino acid sequences, compounds and constructs can be used for prophylactic, therapeutic or diagnostic purposes, such as for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization.

Intranasal delivery of polypeptides and proteins

The present invention relates to the intranasal delivery of therapeutic polypeptides and proteins comprising a Nanobody®, a domain antibody, a single domain antibody or a "dAb". The present invention provides compositions comprising a therapeutically effective amount of such polypeptide or protein and further comprising a pharmaceutically acceptable nasal carrier. The invention also relates to methods for the treatment of a subject comprising the delivery of said polypeptides and proteins to said subject by the nasal route.

COMPOUNDS AND METHODS FOR SPECIFIC CELL TUMOR REDUCTION

Referido un anticuerpo anti-CD25, en donde dicho anticuerpo no inhibe la union de la interleucina-2 (IL-2) a CD25; dicho anticuerpo anti-CD25 compite con el anticuerpo 7G7B6 y/o con el anticuerpo MA251 para unirse al CD25 humano. Tambien se refiere a un metodo para la reduccion celular especifica de tumor. Referred to an anti-CD25 antibody, wherein said antibody does not inhibit the binding of interleukin-2 (IL-2) to CD25; said anti-CD25 antibody competes with antibody 7G7B6 and / or with antibody MA251 to bind to human CD25. It also refers to a method for tumor specific cell reduction.

Cd38 modulating antibody

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

Anti-cd25 for tumor-specific cell depletion (divisional of application no. 202002340)

La presente divulgación proporciona secuencias de anticuerpos encontradas en anticuerpos que se unen a CD25 humana. En particular, la presente divulgación proporciona secuencias de anticuerpos anti–CD25 humanos, que no bloquean la unión de CD25 a IL–2 ni la señalización de IL–2. Los anticuerpos y las porciones de unión a antígeno de los mismos que incluyen dichas secuencias se pueden usar en composiciones farmacéuticas y métodos de tratamiento, en particular para tratar el cáncer. The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides human anti-CD25 antibody sequences, which do not block CD25 binding to IL-2 or IL-2 signaling. Antibodies and antigen-binding portions thereof that include such sequences can be used in pharmaceutical compositions and methods of treatment, in particular to treat cancer.

An ltbr agonist in combination therapy against cancer

The present invention relates to a combination comprising a Treg depletor and an LTBR agonist. Such a combination is particularly useful for use in the treatment of a cancer. Exemplified is the generation of mouse antagonist CCR8 VHH and of CCR8 VHH-Fc fusions as well as the generations of LTBR agonistic single domain antibodies. One anti-CCR8 antibody VHH-Fc and one LTBR agonist VHH have been tested in an MC38 syngeneic mouse model and shown to allow 100% of the tested mice to survive after 25 days, versus 60% with the VHH binding LTBR and 70% with the VHH- Fc binding CCR8. Also exemplified is the effect of a combination of an anti-CTLA4 antibody and a LTBR agonist (VHH-16) on tumor growth im an MC38 syngeneic mouse model resulting in synergism in reducing tumor burden.

Cd38 modulating antibody

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

VEGF UNION MOLECULES

Moléculas de unión a VEGF, preferiblemente dominios variables individuales de inmunoglobulina de unión a VEGF tales como los VHHs y los anticuerpos de dominio, composiciones farmacéuticas que contienen los mismos y su uso en el tratamiento de enfermedades que están asociadas con los efectos sobre la angiogénesis mediados por el VEGF. Ácidos nucleicos que codifican moléculas de unión a VEGF, células hospedantes y métodos para la preparación de los mismos.

Ang2-binding molecules

Disclosed is an Ang2-binding molecule comprising an immunoglobulin single variable domain, wherein said immunoglobulin single variable domain comprises three complementarity determining regions CDR1 , CDR2 and CDR3, wherein CDR1 has an amino acid sequence shown in SEQ ID NO: 168, CDR2 has an amino acid sequence shown in SEQ ID NO: 171 and CDR3 has an amino acid sequence shown in SEQ ID NO: 175 (sequences as defined in the specification).

FC-OPTIMIZED ANTI-CD25 FOR TUMOR-SPECIFIC CELL DEPLETION

Human ccr8 binders

The present invention relates to human CCR8 (hCCR8) binders, wherein the hCCR8 binder is cross-reactive with a non-human primate CCR8. Such binders are particularly useful for the depletion of intra-tumoural regulatory T-cells and immunotherapy in general.

Cd38 modulating antibody

The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

polypeptides against amyloid-beta, nucleic acid encoding such polypeptide, composition comprising such polypeptide, method for producing a polypeptide and use thereof

POLIPEPTìDEOS CONTRA AMILóIDE-BETA, áCIDO NUCLéICO QUE CODIFICA TAL POLIPEPTìDEO, COMPOSIçãO COMPREENDENDO TAL POLIPEPTìDEO, MéTODO PARA PRODUZIR UM POLIPEPTìDEO E USO DO MESMO. A presente invenção refere-se a polipeptídeos anti-A-beta compreendendo pelo menos um Nanobody, ou um fragmento funcional desse, direcionado contra A-beta, para o tratamento de doenças ou distúrbios mediados A-beta ou disf unção dessa, ou mediadas por formação de placa amilóide. Polypeptides against amyloid-beta, nucleic acid encoding such polypeptide, composition comprising such polypeptide, method for producing polypeptide and use thereof. The present invention relates to anti-A-beta polypeptides comprising at least one Nanobody, or a functional fragment thereof, directed against A-beta, for the treatment of A-beta mediated diseases or disorders, or mediated by them. amyloid plaque formation.

Anti-cd25 for tumour specific cell depletion

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25- a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: QCVQGYRA and RWTQPQLICTG on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

ANTI-CD25 ANTIBODIES FOR TUMOR-SPECIFIC CELL DELETION

Ang2-binding molecules

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same.

A-BETA UNION POLYPEPTIDES

La invención se refiere a polipéptidos de unión a A-beta biparatópicos y, más específicamente, a polipéptidos de unión a A-beta biparatópicos que comprenden al menos dos dominios variables de inmunoglobulina que se unen a diferentes epítopos de A-beta. La invención también se refiere a secuencias específicas de dichos polipéptidos, métodos de su producción y métodos de uso de los mismos, incluyendo métodos de tratamiento de enfermedades tales como la enfermedad de Alzheimer.

Anti-cd25 antibody agents

La presente divulgación proporciona secuencias de anticuerpos encontradas en anticuerpos que se unen a CD25 humana. En particular, la presente divulgación proporciona secuencias de anticuerpos anti–CD25 humanos, que no bloquean la unión de CD25 a IL–2 ni la señalización de IL–2. Los anticuerpos y las porciones de unión a antígeno de los mismos que incluyen dichas secuencias se pueden usar en composiciones farmacéuticas y métodos de tratamiento, en particular para tratar el cáncer. The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides human anti-CD25 antibody sequences, which do not block CD25 binding to IL-2 or IL-2 signaling. Antibodies and antigen-binding portions thereof that include such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Vegf-binding molecules.

Moléculas de unión a VEGF, preferiblemente dominios variables individuales de inmunoglobulina de unión a VEGF tales como los VHHs y los anticuerpos de dominio, composiciones farmacéuticas que contienen los mismos y su uso en el tratamiento de enfermedades que están asociadas con los efectos sobre la angiogénesis mediados por el VEGF. Ácidos nucleicos que codifican moléculas de unión a VEGF, células hospedantes y métodos para la preparación de los mismos.

Ang2-binding molecules

Ang2-binding molecules, preferably Ang2-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with Ang2-mediated effects on angiogenesis. Nucleic acids encoding Ang2-binding molecules, host cells and methods for preparing same.

ANTI-CD25 FOR THE DEPLETION OF SPECIFIC TUMOR CELLS

La presente divulgacion proporciona secuencias de anticuerpos encontradas en anticuerpos que se unen a CD25 humana. En particular, la presente divulgacion proporciona secuencias de anticuerpos anti-CD25 humanos, que no bloquean la union de CD25 a IL-2 ni la senalizacion de IL-2. Los anticuerpos y las porciones de union a antigeno de los mismos que incluyen dichas secuencias se pueden usar en composiciones farmaceuticas y metodos de tratamiento, en particular para tratar el cancer The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides human anti-CD25 antibody sequences, which do not block CD25 binding to IL-2 or IL-2 signaling. Antibodies and antigen-binding portions thereof that include such sequences can be used in pharmaceutical compositions and methods of treatment, in particular to treat cancer.

Immunoglobulin single variable domains directed against cxcr7

The present invention relates to particular immunoglobulin single variable domains that bind to human CXCR7, nucleic acids encoding such, domains; to methods for preparing such domains; to host cells expressing or capable of expressing such domains; to compositions and in particular to pharmaceutical compositions that comprise such domains, for prophylactic, therapeutic or diagnostic purposes.

Ang2-binding molecules

Single domain camelide anti-amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenarative neural diseases such as Alzheimer's disease

Bispecific anti-cxcr7 immunoglobulin single variable domains

The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth.

Μορια δεσμευσης-ang2

Μόρια δέσμευσης-Ang2, προτιμώμενα μονές μεταβλητές επικράτειες ανοσοσφαιρινών δέσμευσης-Ang2 όπως τα VHH και αντισώματα επικρατειών, φαρμακευτικές συνθέσεις περιέχοντας τα ίδια και η χρήση αυτών στην αγωγή παθήσεων που συσχετίζονται με Αng2-μεσολαβούμενες επιδράσεις σε αγγειογένεση. Πυρηνικά οξέα εγκωδικεύοντας μόρια δέσμευσης-Ang2, κύτταρα ξενιστών και μέθοδοι για παρασκευή των ιδίων.

Anti-cd25 for tumour specific cell depletion

Verfahren, zusammensetzungen und verbindungstests zur hemmung der amyloid-beta-proteinproduktion

Fc-optimized anti-cd25 for tumour specific cell depletion