Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Compositions and methods for crystallizing antibody fragments

The invention provides methods of crystallizing antibodies and fragments thereof as well as crystals produced thereby. More particularly, the invention provides methods of crystallizing human and non-human Fab fragments of antibodies, either alone or as co-crystals with their target ligand. For example, a crystal comprising a murine Fab fragment of the antibody 125-2H or a human Fab fragment of the antibody ABT-325, which bind to IL-18, are provided as well as a co-crystal of a murine Fab fragment bound to IL-18. ABT-325 and 125-2H differ significantly in combining site character and architecture, thus explaining their ability to bind IL-18 simultaneously at distinct epitopes.

IL-1 BINDING PROTEINS

The present invention encompasses IL-1α binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1α and neutralize IL-1α activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1α and for inhibiting IL-1α activity, e.g., in a human subject suffering from a disorder in which IL-1α activity is detrimental. 147-. (canceled)48. A method for reducing human IL-1α activity in a human subject suffering from a disorder in which IL-1α activity is detrimental comprising administering to the human subject an antibody comprising a variable heavy chain domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 37 , SEQ ID NO: 38 , SEQ ID NO: 39 , SEQ ID NO: 40 , SEQ ID NO: 48 , SEQ ID NO: 50 , SEQ ID NO: 52 , and SEQ ID NO: 54; and a variable light chain domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 41 SEQ ID NO: 42 , SEQ ID NO: 43 , SEQ ID NO: 44 , SEQ ID NO: 45 , SEQ ID NO: 46 , SEQ ID NO: 47 , SEQ ID NO: 49 , SEQ ID NO: 51 , SEQ ID NO: 53 , and SEQ ID NO: 55; wherein the antibody is capable of specifically binding human IL-1α such that human IL-1α activity in the human subject is reduced.49. A method for treating a subject for a disease or a disorder in which IL-1α activity is detrimental comprising administering to the subject an antibody comprising a variable heavy chain domain comprising an amino acid sequence selected from the group consisting ID NO: 40 , SEQ ID NO: 48 , SEQ ID NO: 50 , SEQ ID NO: 52 , and SEQ ID NO: 54; and a variable light chain domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 41 SEQ ID NO: 42 , SEQ ID ...

ANTI-IL1ALPHA/BETA DUAL VARIABLE DOMAIN IMMUNOGLOBULIN AND USES THEREOF

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 1. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein VD1 is a first variable domain , VD2 is a second variable domain , C is a constant domain , X1 represents an amino acid or polypeptide , X2 represents an Fc region and n is 0 or 1 , wherein said binding protein is capable of binding IL-1α and IL-1β.2. The binding protein according to claim 1 , wherein said VD1 and VD2 are heavy chain variable domains.35-. (canceled)6. The binding protein according to claim 2 , wherein C is a heavy chain constant domain.7. The binding protein according to claim 6 , wherein X1 is a linker with the proviso that X1 is not CH1.9. The binding protein according to claim 7 , wherein X2 is an Fc region.10. The binding protein according to claim 9 , wherein said Fc region is a variant Fc region.11. A binding protein comprising a polypeptide chain claim 9 , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n claim 9 , wherein VD1 is a first heavy chain variable domain claim 9 , VD2 is a second heavy chain variable domain claim 9 , C is a heavy chain constant domain claim 9 , X1 is a linker with the proviso that it is not CH1 claim 9 , and X2 is an Fc region.12. The binding protein according to claim 1 , wherein said VD1 and VD2 are light chain variable domains.1315-. (canceled)16. The binding protein according to claim 12 , wherein C is a light chain constant domain.17. The binding protein according to claim 16 , wherein X1 is a linker with the proviso that X1 is not CL1.19. The binding protein according to claim 17 , wherein the binding protein does not comprise X2.20. (canceled)21. A binding protein comprising four polypeptide chains claim 17 , wherein:a first polypeptide chain ...

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

ANTI-TNF/IL-17 DUAL VARIABLE DOMAIN IMMUNOGLOBULIN AND USES THEREOF

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 1. A binding protein comprising a polypeptide chain , wherein the polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein VD1 is a first variable domain , VD2 is a second variable domain , C is a constant domain , X1 represents an amino acid or polypeptide , X2 represents an Fc region and n is 0 or 1 , wherein the binding protein is capable of binding TNF and IL-17.2. The binding protein of claim 1 , wherein the VD1 and the VD2 are heavy chain variable domains.35-. (canceled)6. The binding protein of claim 2 , wherein C is a heavy chain constant domain.7. The binding protein of claim 6 , wherein X1 is a linker with the proviso that X1 is not CH1.8. The binding protein of claim 7 , wherein the linker is AKTTPKLEEGEFSEAR; AKTTPKLEEGEFSEARV; AKTTPKLGG; SAKTTPKLGG; AKTTPKLEEGEFSEARV; SAKTTP; SAKTTPKLGG; RADAAP; RADAAPTVS; RADAAAAGGPGS; RADAAAA(GS) claim 7 , SAKTTP; SAKTTPKLGG; SAKTTPKLEEGEFSEARV; ADAAP; ADAAPTVSIFPP; TVAAP; TVAAPSVFIFPP; QPKAAP; QPKAAPSVTLFPP; AKTTPP; AKTTPPSVTPLAP; AKTTAP; AKTTAPSVYPLAP; ASTKGP; ASTKGPSVFPLAP; GGGGSGGGGSGGGGS; GENKVEYAPALMALS; GPAKELTPLKEAKVS; or GHEAAAVMQVQYPAS.910-. (canceled)11. A binding protein comprising a polypeptide chain claim 7 , wherein the polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n claim 7 , wherein VD1 is a first heavy chain variable domain claim 7 , VD2 is a second heavy chain variable domain claim 7 , C is a heavy chain constant domain claim 7 , X1 is a linker with the proviso that it is not CH1 claim 7 , and X2 is an Fc region claim 7 , wherein the binding protein is capable of binding TNF and IL-17.12. The binding protein of claim 11 , wherein the VD1 and the VD2 are light chain variable domains.1315-. (canceled)16. The binding protein of claim 12 , wherein C is a light chain ...

Dual variable domain immunoglobulins and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

IL-1 binding proteins

The present invention encompasses IL-1 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1 and neutralize IL-1 activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1 and for inhibiting IL-1 activity, e.g., in a human subject suffering from a disorder in which IL-1 activity is detrimental.

Fabs-in-tandem immunoglobulin and uses thereof

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

IL-I binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND USES THEREOF

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease. 176-. (canceled)77. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein;VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;C is a heavy chain constant domain;X1 is a linker;X2 is an Fc region; andwherein the binding protein is capable of binding a pair of antigens selected from the group consisting of TNF and IL-17A; TNF and RANKL; TNF and VEGF; TNF and SOST; TNF and DKK; TNF and alphaVbeta3; TNF and NGF; TNF and IL-23p19; TNF and IL-6; TNF and IL-6R; TNF and CD-20; IgE and IL-13; IL-13 and IL-23p19; IgE and IL-4; IgE and IL-9; IL-13 and IL-9; IL-13 and IL-4; IL-6R and VEGF; IL-6R and IL-17A; IL-6R and RANKL; IL-17A and IL-I beta; IL-I beta and RANKL; IL-L beta and VEGF; and RANKL and CD-20.78. The binding protein according to claim 77 , wherein VD1 and VD2 heavy chain each independently comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 28 claim 77 , 30 claim 77 , 32 claim 77 , 34 claim 77 , 36 claim 77 , 38 claim 77 , 40 claim 77 , 42 claim 77 , 44 claim 77 , 46 claim 77 , 48 claim 77 , 50 claim 77 , 54 claim 77 , 56 claim 77 , 58 claim 77 , 60 claim 77 , 62 claim 77 , 64 claim 77 , 66 claim 77 , and 70 and wherein the VD1 and VD2 light chain variable domains each independently comprise an amino acid sequence selected from the group of consisting of SEQ ID NOs: 29 claim 77 , 31 claim 77 , 33 claim 77 , 35 claim 77 , 37 claim 77 , 39 claim 77 , 41 claim 77 , 43 claim 77 , 45 claim 77 , 47 claim 77 , 49 claim 77 , 51 claim 77 , 55 claim 77 , 57 claim 77 , 59 claim 77 , 61 claim 77 , 63 claim 77 , 65 claim 77 , 67 claim 77 , and 71.79. The binding protein according to claim 77 , wherein X1 comprises an amino acid sequence selected ...

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Fabs-in-tandem immunoglobulin and uses thereof

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

IL-1 BINDING PROTEINS

The present invention describes IL-1β binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1β. Binding proteins of the invention have high affinity for IL-1β and neutralize IL-1β activity. A binding protein of the invention can be a full-length antibody or an IL-1β-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1β binding proteins of the invention are useful for detecting IL-1β and for inhibiting IL-1β activity, including in a human subject suffering from a disease or disorder in which IL-1β activity is detrimental.

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

IL-1 Binding Proteins

The present invention encompasses IL-1 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1 and neutralize IL-1 activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1 and for inhibiting IL-1 activity, e.g., in a human subject suffering from a disorder in which IL-1 activity is detrimental.

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

ANTI-ROR1 ANTIBODIES AND RELATED BISPECIFIC BINDING PROTEINS

Provided herein are antibodies recognizing receptor tyrosine kinase-like orphan receptor 1 (ROR1), bispecific ROR1/CD3 binding proteins such as FIT-Ig and MAT-Fab binding proteins, and the use of the antibodies and bispecific binding proteins for treating hematopoietic cancers and solid tumors.

IL-1 BINDING PROTEINS

The present invention describes IL-1β binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1β. Binding proteins of the invention have high affinity for IL-1β and neutralize IL-1β activity. A binding protein of the invention can be a full-length antibody or an IL-1β-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1β binding proteins of the invention are useful for detecting IL-1β and for inhibiting IL-1β activity, including in a human subject suffering from a disease or disorder in which IL-1β activity is detrimental. 1. (canceled)2. A binding protein that is capable of binding to IL-1β , wherein said binding protein comprises at least one complementarity determining region (CDR) comprising an amino acid sequence selected from the group consisting of residues 31-35 of SEQ ID NO:26 (CDR-H1); residues 50-65 of SEQ ID NO:26 (CDR-H2); residues 98-111 of SEQ ID NO:26 (CDR-H3); residues 24-34 of SEQ ID NO:27 (CDR-L1); residues 50-56 of SEQ ID NO:27 (CDR-L2); and residues 89-97 of SEQ ID NO:27 (CDR-L3).36-. (canceled)7. The binding protein of claim 2 , further comprising a human acceptor framework sequence.8. The binding protein of claim 7 , wherein the human acceptor framework sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:10-25.9. The binding protein of claim 8 , wherein said human acceptor framework sequence comprises at least one amino acid substitution claim 8 , wherein the amino acid sequence of the human acceptor framework sequence is at least 60% identical to an amino acid sequence of any one of SEQ ID NOs:10-25.1013-. (canceled)14. The binding protein of claim 2 , wherein said binding protein has greater than 90% identity to a binding protein comprising a variable heavy chain polypeptide and a variable light chain polypeptide comprising the amino acid sequences of SEQ ID NO: 30 and SEQ ID NO: 34 claim 2 , ...

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Dual variable domain immunnoglobulins and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND USES THEREOF

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

INTERLEUKIN-13 BINDING PROTEINS

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental. 1. A binding protein comprising an antigen binding domain , said binding protein capable of binding IL-13 , said antigen binding domain comprising six CDRs: CDR-H1 , CDR-H2 , CDR-H3 , CDR-L1 , CDR-L2 , and CDR-L3 , wherein the CDRs of the binding protein comprise one or more of: [{'sub': 1', '2', '3', '4', '5', '6', '7, 'claim-text': [{'sub': '1', 'Xis T, D, G, or S;'}, {'sub': '2', 'Xis S;'}, {'sub': '3', 'Xis D;'}, {'sub': '4', 'Xis M, S, Y, L, or H;'}, {'sub': '5', 'Xis G, W, Y, A, S, or N;'}, {'sub': '6', 'Xis V, I, or M; and'}, {'sub': '7', 'Xis D, H, S, Y, N, or G;'}], '(a) X-X-X-X-X-X-X(SEQ ID NO: 64), wherein'}, '(b) residues 31-35 of SEQ ID NO:32;', '(c) residues 31-35 of SEQ ID NO:34;', '(d) residues 31-35 of SEQ ID NO:36;', '(e) residues 31-35 of SEQ ID NO:38;', '(f) residues 31-35 of SEQ ID NO:39;', '(g) residues 31-35 of SEQ ID NO:41;', '(h) residues 31-35 of SEQ ID NO:42;', '(i) residues 31-35 of SEQ ID NO:44;', '(j) residues 31-37 of SEQ ID NO:46;', '(k) residues 31-37 of SEQ ID NO:48;', '(l) residues 31-37 of SEQ ID NO:50;', '(m) residues 31-35 of SEQ ID NO:52;', '(n) residues 31-35 of SEQ ID NO:54;', '(o) residues 31-35 of SEQ ID NO:56;', '(p) residues 31-35 of SEQ ID NO:58;', '(l) residues 31-35 of SEQ ID NO:60; and', '(r) residues 31-35 of SEQ ID NO:62;, '(i) CDR-H1 comprising an amino acid ...

IL-1 ALPHA DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND USES THEREOF

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease. 176-. (canceled)78. The binding protein of claim 77 , wherein the variable domains that form a functional target binding site for IL-1α comprise SEQ ID NO: 68 and SEQ ID NO: 69.80. The binding protein of claim 79 , wherein the variable domains that form a functional target binding site for IL-1α comprise SEQ ID NO: 68 and SEQ ID NO: 69.81. The binding protein of claim 79 , wherein VD1 is a first heavy chain variable domain;', 'VD2 is a second heavy chain variable domain;', 'C is a heavy chain constant domain;', 'X1 is a linker;', 'X2 is an Fc region;', 'n is 0 or 1; and, '(a) the first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein'} VD1 is a first light chain variable domain;', 'VD2 is a second light chain variable domain;', 'C is a light chain constant domain;', 'X1 is a linker;', 'n is 0 or 1 for (X1)n; and', 'n is 0 for (X2)n., '(b) the second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein'}82. The binding protein of claim 79 , comprising two first polypeptide chains and two second polypeptide chains and four functional target binding sites.83. The binding protein of claim 79 , wherein the binding protein has{'sub': 'on', 'sup': 2', '−1', '−1', '3', '−1', '−1', '4', '−1', '−1', '5', '−1', '−1', '6', '−1', '−1, '(a) an on rate constant (K) to at least one target of at least about 10Ms; at least about 10Ms; at least about 10Ms; at least about 10Ms; or at least about 10Ms; as measured by surface plasmon resonance;'}{'sub': 'off', 'sup': −3', '−1', '−4', '−1', '−5', '−1', '−6', '−1, '(b) an off rate constant (K) to at least one target of at most about 10s; at most about 10s; at most about 10s; or at most about 10s, as measured by surface plasmon resonance; or'}{'sub': 'D', 'sup': −7', '−8', '−9', '−10', '−11', '−12', '−13, '(c) ...

Dual Variable Domain Immunoglobulins and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

IL-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Dual Variable Domain Immunoglobulins and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

INTERLEUKIN-13 BINDING PROTEINS

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Dual Variable Domain Immunnoglobulins and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease. 1. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein;VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region; andn is 0 or 1;wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of IL-1alpha and IL-1beta.2. The binding protein according to claim 1 , wherein VD1 and VD2 comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 30 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 38 claim 1 , 40 claim 1 , 42 claim 1 , 44 claim 1 , and 46.3. A binding protein comprising a polypeptide chain claim 1 , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n claim 1 , wherein;VD1 is a first light heavy chain variable domain;VD2 is a second light heavy chain variable domain;C is a light chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 does not comprise an Fc region; andn is 0 or 1;wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of IL-1alpha (seq. 3) and IL-1beta (seq. 1); IL-1alpha (seq. 2) and IL-1beta (seq. 1); IL-1alpha (seq. 1) and IL-1beta (seq. 1); IL-1alpha (seq. 3) and IL-1beta (seq. 2); IL-1alpha (seq. 4) and IL-1beta (seq. 2); IL-1alpha (seq. 4) and IL-1beta (seq. 3); IL-1alpha (seq. 4) and IL-1beta (seq. 4); IL-1alpha (seq. 4) and IL-1beta (seq. 5).4. The binding protein according to claim 3 , wherein the VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 31 claim 3 , 33 claim 3 , 35 claim 3 , 37 claim 3 , 39 claim 3 , 41 claim ...

TGF[beta]/PD-L1 BISPECIFIC BINDING PROTEINS

The present invention relates to bispecific binding proteins that bind TGFβ and PD-L1, and novel anti-PD-L1 antibodies, methods of making the bispecific binding proteins and antibodies, compositions comprising the bispecific binding proteins or antibodies, and methods of using the bispecific binding proteins for blocking TGFβ-mediated suppression of T cell activation, for blocking PD-L1-mediated suppression of T cell activation, and for treating cancer.

IL-1 binding proteins

The present invention describes IL-1 binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1. Binding proteins of the invention have high affinity for IL-1 and neutralize IL-1 activity. A binding protein of the invention can be a full-length antibody or an IL-1-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1 binding proteins of the invention are useful for detecting IL-1 and for inhibiting IL-1 activity, including in a human subject suffering from a disease or disorder in which IL-1 activity is detrimental.

Interleukin-13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo. 1. A method of treating or preventing a disease in a subject in need thereof , the method comprising administering to the subject an effective amount of a composition comprising a binding protein , said binding protein comprising three polypeptide chains ,{'sub': A', 'B', 'B', 'B', 'A', 'A, 'wherein the first polypeptide chain comprises, from amino terminus to carboxyl terminus, either (i) VL-CL-VH-CH1-Fc, wherein CL is fused directly to VH, or (ii) VH-CH1-VL-CL-Fc, wherein CH1 is fused directly to VL,'}{'sub': 'A', 'wherein the second polypeptide chain comprises, from amino terminus to carboxyl terminus, VH-CH1,'}{'sub': 'B', 'wherein the third polypeptide chain comprises, from amino terminus to carboxyl terminus, VL-CL,'}wherein A is a first epitope or antigen, and B is a second epitope or antigen, and wherein A and B are different epitopes of the same antigen or are different antigens, which antigen or antigens are related to said disease;{'sub': A', 'B', 'A', 'B, 'wherein VLis a light chain variable domain of a first parental antibody that binds A, CL is an antibody light chain constant domain, VHis a heavy chain variable domain of a second parental antibody that binds B, CH1 is a first constant domain of an antibody heavy chain, VHis a heavy chain variable domain of said first parental antibody that binds A, and VLis a light chain variable domain of said second parental antibody that binds B;'}wherein the binding protein binds to both A and B; andwherein the binding protein comprises two of said first polypeptide chains, two of said second ...

TRI-VARIABLE DOMAIN BINDING PROTEINS AND USES THEREOF

The present invention provides engineered multivalent and multispecific binding proteins, as well as methods of making them. Methods for using the multivalent and multispecific binding proteins of the invention in the prevention, diagnosis, and/or treatment of disease are also provided. 1. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-(X2)n-VD3-C-(X3)n , wherein;VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;VD3 is a third heavy chain variable domain;C is a heavy chain constant domain;X1 is a first linker;X2 is a second linker;X3 is an Fc region; andn is 0 or 1;wherein the binding protein is capable of binding one to three target antigens.2. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-(X2)n-VD3-C-(X3)n , wherein;VD1 is a first light chain variable domain;VD2 is a second light chain variable domain;VD3 is a third light chain variable domain;C is a light chain constant domain;X1 is a first linker;X1 is a second linker;X3 does not comprise an Fc region; andn is 0 or 1;wherein the binding protein is capable of binding one to three target antigens.3. A binding protein comprising a first and a second polypeptide chain , wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-(X2)n-VD3-C-(X3)n , whereinVD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;VD3 is a third heavy chain variable domain;C is a heavy chain constant domain;X1 is a first linker;X2 is a second linker;andX3 is an Fc region; andwherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-(X2)n-VD3-C-(X3)n, wherein VD2 is a second light chain variable domain;', 'VD3 is a third light chain variable domain;', 'C is a light chain constant domain;', 'X1 is a first linker;', 'X2 is a second linker; and', 'X3 does not comprise an Fc region; and', 'n is 0 or 1,, 'VD1 is a first light chain ...

IL-l BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 3. The binding protein according to claim 1 , wherein: said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212.4. The binding protein according to claim 1 , wherein: said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 215.5. The binding protein according to claim 2 , wherein: said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 219.6. The binding protein according to claim 2 , wherein: said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 220.7. The binding protein according to claim 1 , wherein: when said first polypeptide chain comprises the amino acid sequence of SEQ ID NO:212 claim 1 , then said second polypeptide chain comprises the amino acid sequence of SEQ ID NO:215.8. The binding protein according to claim 2 , wherein: said first polypeptide chain comprises SEQ ID NO:219 claim 2 , and said second polypeptide chain comprises SEQ ID NO:220.9. The binding protein according to claim 1 , wherein the binding protein comprises two first polypeptide chains and two second polypeptide chains.10. The binding protein according to claim 1 , wherein X1 or X2 is an amino acid sequence selected from the group consisting of SEQ ID NOs:26-57 claim 1 , 233 claim 1 , 224 claim 1 , and 225.11. The binding protein according to claim 1 , wherein the Fc region is a variant sequence Fc region.12. (canceled)13. A binding protein conjugate comprising a binding protein as described in claim 1 , said binding protein conjugate further comprising an agent selected from the group consisting of: an immunoadhesion molecule claim 1 , an imaging agent claim 1 , a therapeutic agent claim 1 , and a cytotoxic agent.1415-. (canceled)16. The binding protein ...

INTERLEUKIN-13 BINDING PROTEINS

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental. 2. The method according to claim 1 , wherein said polymeric carrier is a polymer selected from one or more of the group consisting of: poly(acrylic acid) claim 1 , poly(cyanoacrylates) claim 1 , poly(amino acids) claim 1 , poly(anhydrides) claim 1 , poly(depsipeptide) claim 1 , poly(esters) claim 1 , poly(lactic acid) claim 1 , poly(lactic-co-glycolic acid) or PLGA claim 1 , poly(b-hydroxybutryate) claim 1 , poly(caprolactone) claim 1 , poly(dioxanone); poly(ethylene glycol) claim 1 , poly((hydroxypropyl) methacrylamide claim 1 , poly [(organo) phosphazene] claim 1 , poly(ortho esters) claim 1 , poly(vinyl alcohol) claim 1 , poly(vinylpyrrolidone) claim 1 , maleic anhydride-alkyl vinyl ether copolymers claim 1 , pluronic polyols claim 1 , albumin claim 1 , alginate claim 1 , cellulose and cellulose derivatives claim 1 , collagen claim 1 , fibrin claim 1 , gelatin claim 1 , hyaluronic acid claim 1 , oligosaccharides claim 1 , glycaminoglycans claim 1 , sulfated polysaccharides claim 1 , blends and copolymers thereof.3. The method according to claim 1 , wherein said ingredient is selected from the group consisting of albumin claim 1 , sucrose claim 1 , trehalose claim 1 , lactitol claim 1 , gelatin claim 1 , hydroxypropyl-β-cyclodextrin claim 1 , methoxypolyethylene glycol and polyethylene glycol. ...

Il-1 binding proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 175-. (canceled)76. A binding protein comprising first and second polypeptide chains , each independently comprising VD1-(X1)n-VD2-C-(X2)n , whereinVD1 is a first variable domain;VD2 is a second variable domain;C is a constant domain;X1 is a linker;X2 is an Fc region; andn is 0 or 1;wherein the VD1 domains on the first and second polypeptide chains form a functional target binding site and the VD2 domains on the first and second polypeptide-chains form a functional target binding site, and wherein at least one functional target site binds to TNF.77. The binding protein of claim 76 , wherein the variable domains that form the functional target binding site for TNF comprise variable domains from adalimumab (HUMIRA®) claim 76 , infliximab (REMICADE®) claim 76 , HUMICADE® claim 76 , CNTO 148 (Medarex/Centocor) or etenercept (ENBREL®).78. The binding protein of claim 76 , wherein the binding protein also binds to a cytokine claim 76 , cytokine receptor claim 76 , or a cytokine related protein.79. The binding protein of claim 76 , wherein the binding protein also binds to a target selected from the group consisting of ABCF1 claim 76 , ACVRI claim 76 , ACVR1B claim 76 , ACVR2 claim 76 , ACVR2B claim 76 , ACVRL1 claim 76 , AMH claim 76 , AMHR2 claim 76 , BMPR1A claim 76 , BMPR1B claim 76 , BMPR2 claim 76 , BCL6 claim 76 , C19orf10 (IL27w) claim 76 , C3 claim 76 , C4A claim 76 , C5 claim 76 , CNR1 claim 76 , CRP claim 76 , CTLA4 claim 76 , CYSLTR1 claim 76 , BLR1 claim 76 , CCL1 (1-309) claim 76 , CCL2 (mcp-1) claim 76 , CCL3 (MIP-1a) claim 76 , CCL4 (MIP-1b) claim 76 , CCL5 (RANTES) claim 76 , CCL7 (mcp-3) claim 76 , CCL8 (mcp-2) claim 76 , CCL11 (eotaxin) claim 76 , CCL13 (mcp-4) claim 76 , CCL15 (MIP-Id) claim 76 ,CCL16 (HCC-4) claim 76 , CCL17 ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 1. A binding protein comprising a polypeptide chain , wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein VD1 is a first variable domain , VD2 is a second variable domain , C is a constant domain , X1 represents an amino acid or polypeptide , X2 represents an Fc region and n is 0 or 1 , wherein said binding protein is capable of binding one or more targets.2. The binding protein according to claim 1 , wherein said VD1 and VD2 are heavy chain variable domains.3. The binding protein according to claim 2 , wherein said heavy chain variable domain is selected from the group consisting of a murine heavy chain variable domain claim 2 , a human heavy chain variable domain claim 2 , a CDR grafted heavy chain variable domain claim 2 , and a humanized heavy chain variable domain.4. The binding protein according to claim 2 , wherein VD1 and VD2 are capable of binding the same antigen.5. The binding protein according to claim 2 , wherein VD1 and VD2 are capable of binding different antigens.6. The binding protein according to claim 2 , wherein C is a heavy chain constant domain.7. The binding protein according to claim 6 , wherein X1 is a linker with the proviso that X1 is not CH1.8. The binding protein according to claim 7 , wherein the linker is selected from the group consisting of AKTTPKLEEGEFSEAR (SEQ ID NO:118); AKTTPKLEEGEFSEARV (SEQ ID NO:119); AKTTPKLGG (SEQ ID NO:120); SAKTTPKLGG (SEQ ID NO:121); SAKTTP (SEQ ID NO:122); RADAAP (SEQ ID NO:123); RADAAPTVS (SEQ ID NO:124); RADAAAAGGPGS (SEQ ID NO:125); RADAAAA(GS)(SEQ ID NO:126) SAKTTPKLEEGEFSEARV (SEQ ID NO:127); ADAAP (SEQ ID NO:40); ADAAPTVSIFPP (SEQ ID NO:103); TVAAP (SEQ ID NO:44); TVAAPSVFIFPP (SEQ ID NO:50); QPKAAP (SEQ ID NO:88); QPKAAPSVTLFPP (SEQ ID NO:92); AKTTPP ...

IL-1 BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 1. A binding protein comprising first and second polypeptide chains , wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n , wherein:VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region; andn is independently 0 or 1; andwherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n,wherein:VD1 is a first light chain variable domain;VD2 is a second light chain variable domain;C is a light chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 does not comprise an Fc region; andn is independently 0 or 1;wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 60-148, 196, 198, 200, 202, 204, 206, 208 and 210; and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 213 and 227;wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 149-189, 197, 199, 201, 203, 205, 207, 209 and 211; and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 216 and 229; andwherein the binding protein binds human IL-1β and human IL-1α.2. A binding protein comprising first and second polypeptide chains , wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n , wherein:VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region; andn is independently 0 or 1; andwherein said second polypeptide ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 1. A method for treating a human subject for a disease or a disorder by administering to the subject a binding protein comprising four polypeptide chains wherein:each of two polypeptide chains comprises VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first heavy chain variable domain, VD2 is a second heavy chain variable domain, C is a constant domain, X1 is a linker with the proviso that it is not a constant domain, X2 is an Fc region, and n is 0 or 1; andeach of two polypeptide chains comprises VD1-(X1)n-VD2-C, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a constant domain, and X1 is a linker with the proviso that it is not a constant domain, and n is 0 or 1;wherein the four polypeptide chains of the binding protein form four functional target binding sites; andwherein the binding protein binds a target or targets that are detrimental to the human subject suffering from the disease or disorder such that the activity of the target or targets in the human subject is inhibited such that treatment is achieved.2. The method of claim 1 , wherein the step of administering to the subject is by at least one mode selected from the group consisting of parenteral claim 1 , subcutaneous claim 1 , intramuscular claim 1 , intravenous claim 1 , intraarticular claim 1 , intrabronchial claim 1 , intraabdominal claim 1 , intracapsular claim 1 , intracartilaginous claim 1 , intracavitary claim 1 , intracelial claim 1 , intracerebellar claim 1 , intracerebroventricular claim 1 , intracolic claim 1 , intracervical claim 1 , intragastric claim 1 , intrahepatic claim 1 , intramyocardial claim 1 , intraosteal claim 1 , intrapelvic claim 1 , intrapericardiac claim 1 , intraperitoneal claim 1 , intrapleural claim 1 ...

IL-1 BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 1117-. (canceled)118. A method for reducing human IL-1 activity in a human subject suffering from a disorder in which IL-1 activity is detrimental , comprising administering to the human subject a binding protein or a crystal thereof , wherein the binding protein comprises an antigen binding domain , said binding protein capable of binding human IL-1β , said antigen binding domain comprising six CDRs:CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below:{'sub': '1', 'claim-text': {'sub': '1', 'Xis S, K or R;'}, 'CDR-H1: X-Y-D-M-S (SEQ ID NO:190), wherein;'}{'sub': 2', '4', '7', '14', '15, 'claim-text': [{'sub': '2', 'Xis I or V;'}, {'sub': '4', 'Xis S or H;'}, {'sub': '7', 'Xis G or A;'}, {'sub': '14', 'Xis T or S; and'}, {'sub': '15', 'Xis V or A;'}], 'CDR-H2: Y-X-S-X-G-G-X-G-T-Y-Y-P-D-X-X-K-G (SEQ ID NO:191), wherein;'}{'sub': 4', '7', '10, 'claim-text': [{'sub': '4', 'Xis T or Y;'}, {'sub': '7', 'Xis Y or C; and'}, {'sub': '10', 'Xis V, E, L, M, Q, or Y;'}], 'CDR-H3: G-G-V-X-K-G-X-F-D-X(SEQ ID NO:192), wherein;'}{'sub': 7', '8', '9', '11, 'claim-text': [{'sub': '7', 'Xis H, Y, or W;'}, {'sub': '8', 'Xis N, G, T, Q, E, H, D, or K;'}, {'sub': '9', 'Xis Y or W; and'}, {'sub': '11', 'Xis T, A, or N;'}], 'CDR-L1: R-A-S-G-N-I-X-X-X-L-X(SEQ ID NO:193), wherein;'}{'sub': 1', '4', '6', '7, 'claim-text': [{'sub': '1', 'Xis N, Q or D;'}, {'sub': '4', 'Xis T, N, I, E, or S;'}, {'sub': '6', 'Xis A, M, or E; and'}, {'sub': '7', 'Xis D, E, S, or A;'}], 'CDR-L2: X-A-K-X-L-X-X(SEQ ID NO:194), wherein;'}and{'sub': 2', '5', '6', '8', '9, 'claim-text': [{'sub': '2', 'Xis H or Q;'}, {'sub': '5', 'Xis S, N, T, K, R, or M;'}, {'sub': '6', 'Xis I or L;'}, {'sub': '8', 'Xis Y or A; and'}, {'sub': '9', 'Xis T, I, and N;'}], 'CDR-L3: Q-X ...

IL-1 BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 146-. (canceled)48122-. (canceled)123. The method according to claim 47 , wherein administering to the subject is by at least one route selected from the group consisting of: parenteral claim 47 , subcutaneous claim 47 , intramuscular claim 47 , intravenous claim 47 , intra-articular claim 47 , intrabronchial claim 47 , intraabdominal claim 47 , intracapsular claim 47 , intracartilaginous claim 47 , intracavitary claim 47 , intracelial claim 47 , intracerebellar claim 47 , intracerebroventricular claim 47 , intracolic claim 47 , intracervical claim 47 , intragastric claim 47 , intrahepatic claim 47 , intramyocardial claim 47 , intraosteal claim 47 , intrapelvic claim 47 , intrapericardiac claim 47 , intraperitoneal claim 47 , intrapleural claim 47 , intraprostatic claim 47 , intrapulmonary claim 47 , intrarectal claim 47 , intrarenal claim 47 , intraretinal claim 47 , intraspinal claim 47 , intrasynovial claim 47 , intrathoracic claim 47 , intrauterine claim 47 , intravesical claim 47 , bolus claim 47 , vaginal claim 47 , rectal claim 47 , buccal claim 47 , sublingual claim 47 , intranasal claim 47 , and transdermal.124. The method according to claim 47 , wherein administering comprises injecting the binding protein.125. The method according to claim 47 , further comprising administering at least one additional agent.126. The method according to claim 125 , wherein the at least one additional agent is a therapeutic agent.127. The method according to claim 126 , wherein the therapeutic agent comprises at least one selected from the group consisting of: an inhaled steroid; a beta-agonist; a short-acting beta-agonist; a long-acting beta-agonist; an antagonist of a leukotriene; an antagonist of a leukotriene receptor; ADVAIR™; an ...

IL-1 BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 1101-. (canceled)103. A vector comprising an isolated nucleic acid according to .104. The vector according to claim 103 , wherein said vector is selected from the group consisting of pcDNA claim 103 , pTT claim 103 , pTT3 claim 103 , pEFBOS claim 103 , pBV claim 103 , pJV claim 103 , and pBJ.105. A host cell comprising a vector according to .106. The host cell according to claim 105 , wherein said host cell is a prokaryotic cell.107Escherichia coli.. The host cell according to claim 106 , wherein said prokaryotic host cell is108. The host cell according to claim 105 , wherein said host cell is a eukaryotic cell.109. The host cell according to claim 108 , wherein said eukaryotic cell is selected from the group consisting of: a protist cell claim 108 , an animal cell claim 108 , a plant cell claim 108 , and a fungal cell.110. The host cell according to claim 109 , wherein said fungal cell is a yeast cell.111Saccharomyces cerevisiae.. The host cell according to claim 110 , wherein said yeast cell is112. The host cell according to claim 109 , wherein said animal cell is selected from the group consisting of: a mammalian cell claim 109 , an avian cell claim 109 , and an insect cell.113. The host cell according to claim 112 , wherein said mammalian cell is a CHO cell or a COS cell.114. The host cell according to claim 112 , wherein said insect host cell is an insect Sf9 cell.115. A method of producing an IL-1β binding protein claim 105 , comprising culturing a host cell described in in culture medium under conditions sufficient to produce the IL-1β binding protein.116122-. (canceled) This application claims the benefit of priority of U.S. Provisional Application No. 61/334,917, filed May 14, 2010, and of U.S. Provisional Application ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 175-. (canceled)77. The binding protein of claim 76 , wherein the variable domains that form the functional target binding site for EGFR comprise variable domains from an anti-EGFR antibody selected from cetuximab (ERBITUX® Imclone) claim 76 , ABX-EGF (Abgenix-Immunex-Amgen) claim 76 , HUMAX-EGFR™ (Genmab) claim 76 , EMD55900 (Merck) claim 76 , EMD62000 (Merck) claim 76 , and EMD72000 (Merck).78. The binding protein of claim 76 , wherein the binding protein also binds to a target selected from the group consisting of ABCF1; ACVR1; ACVR1B; ACVR2; ACVR2B; ACVRL1; ADORA2A; Aggrecan; AGR2; AICDA; AIF1; AIG1; AKAP1; AKAP2; AMH; AMHR2; ANGPT1; ANGPT2; ANGPTL3; ANGPTL4; ANPEP; APC; APOC1; AR; AZGP1 (zinc-a-glycoprotein); B7.1; B7.2; BAD; BAFF; BAG1; BAI1; BCL2; BCL6; BDNF; BLNK; BLR1 (MDR15); BlyS; BMP1; BMP2; BMP3B (GDF10); BMP4; BMP6; BMP8; BMPR1A; BMPR1B; BMPR2; BPAG1 (plectin); BRCA1; C19orf10 (IL27w); C3; C4A; C5; C5R1; CANT1; CASP1; CASP4; CAV1; CCBP2 (D6/JAB61); CCL1 (1-309); CCL11 (eotaxin); CCL13 (MCP-4); CCL15 (MIP-1d); CCL16 (HCC-4); CCL17 (TARC); CCL18 (PARC); CCL19 (MIP-3b); CCL2 (MCP-1); MCAF; CCL20 (MIP-3a); CCL21 (MIP-2); SLC; exodus-2; CCL22 (MDC/STC-1); CCL23 (MPIF-1); CCL24 (MPIF-2/eotaxin-2); CCL25 (TECK); CCL26 (eotaxin-3); CCL27 (CTACK/ILC); CCL28; CCL3 (MIP-1a); CCL4 (MIP-1b); CCL5 (RANTES); CCL7 (MCP-3); CCL8 (mcp-2); CCNA1; CCNA2; CCND1; CCNE1; CCNE2; CCR1 (CKR1/HM145); CCR2 (mcp-1RB/RA); CCR3 (CKR3/CMKBR3); CCR4; CCR5 (CMKBR5/ChemR13); CCR6 (CMKBR6/CKR-L3/STRL 22/DRY6); CCR7 (CKR7/EBI1); CCR8 (CMKBR8/TER1/CKR-L1); CCR9 (GPR-9-6); CCRL1 (VSHK1); CCRL2 (L-CCR); CD164; CD19; CD1C; CD20; CD200; CD-22; CD24; CD28; CD3; CD37; CD38; CD3E; CD3G; CD3Z; CD4; CD40; CD40L; CD44; CD45RB; CD52; CD69; CD72; CD74; CD79A; CD79B; CD8; ...

IL-1 BINDING PROTEINS

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 147-. (canceled)49YersiniaSalmonellaStreptococcilegionellamycobacterium aviummycobacterium tuberculosispneumocystis cariniiStreptococcusYersiniaSalmonella. The method of claim 48 , wherein said disorder is selected from the group consisting of: diabetes; uveitis; neuropathic pain; osteoarthritic pain; inflammatory pain; rheumatoid arthritis; osteoarthritis; juvenile chronic arthritis; septic arthritis; Lyme arthritis; psoriatic arthritis; reactive arthritis; spondyloarthropathy; systemic lupus erythematosus (SLE); Crohn's disease; ulcerative colitis; inflammatory bowel disease; autoimmune diabetes; insulin dependent diabetes mellitus; thyroiditis; asthma; allergic diseases; psoriasis; dermatitis; scleroderma; graft versus host disease; organ transplant rejection; acute immune disease associated with organ transplantation; chronic immune disease associated with organ transplantation; sarcoidosis; atherosclerosis; disseminated intravascular coagulation (DIC); Kawasaki's disease; Grave's disease; nephrotic syndrome; chronic fatigue syndrome; Wegener's granulomatosis; Henoch-Schoenlein purpurea; microscopic vasculitis of the kidneys; chronic active hepatitis; autoimmune uveitis; septic shock; toxic shock syndrome; sepsis syndrome; cachexia; infectious diseases; parasitic diseases; acute transverse myelitis; Huntington's chorea; Parkinson's disease; Alzheimer's disease; stroke; primary biliary cirrhosis; hemolytic anemia; malignancies; heart failure; myocardial infarction; Addison's disease; sporadic polyglandular deficiency type I; polyglandular deficiency type II (Schmidt's syndrome); acute respiratory distress syndrome (ARDS); alopecia; alopecia greata; seronegative arthropathy; arthropathy; Reiter's disease; psoriatic arthropathy ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 175-. (canceled)76. A multispecific binding protein comprising functional antigen binding sites for tumor necrosis factor (TNF) and interleukin 17 (IL-17).77. The binding protein of claim 76 , wherein the binding protein is capable of simultaneously binding TNF and IL-17.78. The binding protein of claim 76 , wherein the binding protein is capable of simultaneously neutralizing TNF and IL-17.79. The binding protein of claim 76 , wherein the binding protein comprises an antigen-binding portion of an anti-TNF antibody and an antigen-binding portion of an anti-IL-17 antibody.80. The binding protein of claim 76 , wherein the antigen binding sites for TNF and IL-17 are joined by a linker.81. The binding protein of claim 80 , wherein the linker comprises any one of: SEQ ID NO:38; SEQ ID NO:40; SEQ ID NO:42; SEQ ID NO:44; SEQ ID NO:48; SEQ ID NO:50; SEQ ID NO:88; SEQ ID NO:92; SEQ ID NO:99; SEQ ID NO: 103; and SEQ ID NOs: 118-133.82. The binding protein of claim 76 , wherein the binding protein is a single-chain multispecific binding protein claim 76 , tandem single-chain Fv molecule claim 76 , a bispecific antibody claim 76 , a multispecific antibody claim 76 , a dual-specific antibody claim 76 , a diabody claim 76 , a bispecific diabody claim 76 , a single-chain diabody claim 76 , a diabody fused to an Fc molecule claim 76 , a dual variable domain binding protein claim 76 , a chemical conjugation of two or more antibodies claim 76 , two or more cross-linked antibodies claim 76 , or a derivative thereof.83. The binding protein of claim 76 , wherein the binding protein is affinity-matured claim 76 , chimeric claim 76 , humanized claim 76 , CDR-grafted claim 76 , back-mutated claim 76 , or framework modified.84. The binding protein of claim 76 , ...

HIGH AFFINITY ANTIBODIES TO PD-1 AND LAG-3 AND BISPECIFIC BINDING PROTEINS MADE THEREFROM

High-affinity antibodies recognizing Programmed Death Ligand-1 (PD-1) and Lymphocyte Activation Gene 3 protein (LAG-3) are disclosed. Binding sites from humanized anti-PD-1 and anti-LAG-3 antibodies are incorporated into a Fabs-in-Tandem Immunoglobulin format without significant loss of binding affinity, and the resultant bispecific, multivalent binding proteins are able to bind to both PD-1 and LAG-3 simultaneously. Such bispecific FIT-Ig binding proteins are useful for treatment of cancer. 145-. (canceled)48. An anti-LAG-3 antibody , or an antigen-binding portion thereof , capable of binding human LAG-3 , wherein the antibody or antigen-binding portion thereof comprises a set of six complementarity determining regions (CDRs) , CDR-H1 , CDR-H2 , CDR-H3 , CDR-L1 , CDR-L2 , and CDR-L3 , selected from the group consisting of:CDR-H1 comprising DFNIKDDYMH (residues 26-35 of SEQ ID NO:114), CDR-H2 comprising WIVPENGNTEYASKFQG (residues 50-66 of SEQ ID NO:114), CDR-H3 comprising YGDY (residues 99-102 of SEQ ID NO:114), CDR-L1 comprising RASQEISGYLS (residues 24-34 of SEQ ID NO:117), CDR-L2 comprising AASTLDS (residues 50-56 of SEQ ID NO:117), and CDR-L3 comprising LQYASYPLT (residues 89-97 of SEQ ID NO:117);CDR-H1 comprising DDYMH (residues 31-35 of SEQ ID NO:135), CDR-H2 comprising WIVPENANTVYASKFQG (SEQ ID NO:224), CDR-H3 comprising YGDY (residues 99-102 of SEQ ID NO:135), CDR-L1 comprising RASQEISGYLS (residues 24-34 of SEQ ID NO:138), CDR-L2 comprising AASALDS (residues 50-56 of SEQ ID NO:138), and CDR-L3 comprising LQYASYPLT (residues 89-97 of SEQ ID NO:138);CDR-H1 comprising DDYMH (residues 31-35 of SEQ ID NO:136), CDR-H2 comprising WIVPRNANTVYASKFQG (SEQ ID NO:225), CDR-H3 comprising YGDY (residues 99-102 of SEQ ID NO:136), CDR-L1 comprising RASQEISGYLS (residues 24-34 of SEQ ID NO:139), CDR-L2 comprising AASALDL (residues 50-56 of SEQ ID NO:139), and CDR-L3 comprising LQYASYPLT (residues 89-97 of SEQ ID NO:139); andCDR-H1 comprising DDYMH (residues 31-35 of SEQ ID ...

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo. 2. A binding protein comprising three polypeptide chains , wherein:{'sub': A', 'B', 'B', 'B', 'A', 'A, 'the first polypeptide chain comprises, from amino terminus to carboxyl terminus, either (i) VL-CL-VH-CH1-Fc, wherein CL is fused directly to VH, or (ii) VH-CH1-VL-CL-Fc, wherein CH1 is fused directly to VL, and wherein there are no linkers inserted between the variable domains and constant domains;'}{'sub': A', 'A, 'wherein the second polypeptide chain comprises, from amino terminus to carboxyl terminus, VH—CH1, wherein there is no linker inserted between VHand CH1; and'}{'sub': B', 'B, 'wherein the third polypeptide chain comprises, from amino terminus to carboxyl terminus, VL-CL, wherein there is no linker inserted between VLand CL;'}wherein the binding protein is capable of binding two or more epitopes or antigens, wherein VL is a light chain variable domain, CL is a light chain constant domain, VH is a heavy chain variable domain, CH1 is a first constant domain of a heavy chain, A is a first epitope or antigen, and B is a second epitope or antigen, and wherein A and B are different epitopes of the same antigen or are different antigens;wherein, on expression in a mammalian host cell, two of said first polypeptide chains, two of said second polypeptide chains, and two of said third polypeptide chains associate to provide a monomeric, tetravalent, and bispecific binding protein comprising six polypeptide chains, having four functional Fab binding regions, and wherein said binding protein binds both epitope or antigen A and epitope or antigen B; ...

Monovalent Asymmetric Tandem Fab Bispecific Antibodies

The invention provides monovalent, asymmetric tandem Fab bispecific antibodies that can bind two epitopes or two antigens, compositions comprising such antibodies, uses of such antibodies, methods of making such antibodies, nucleic acids encoding such antibodies, and host cells comprising such nucleic acids. 2. The MAT-Fab antibody according to claim 1 , wherein the one or more KiH mutations in the CH3m1 domain or the CH3m2 domain to form a structural knob is a change from a threonine residue to a tyrosine residue or a change of a threonine residue to a tryptophan residue.3. The MAT-Fab antibody according to claim 2 , wherein the KiH mutation to change a threonine residue to a tyrosine residue changes threonine at position 21 of the CH3 domain to tyrosine.4. The MAT-Fab antibody according to claim 2 , wherein the KiH mutation to change a threonine residue to a tryptophan residue changes threonine at position 21 of the CH3 domain to tryptophan.5. The MAT-Fab antibody according to claim 2 , wherein the KiH mutation to form a structural knob is in the CH3m1 domain of the heavy chain.6. The MAT-Fab antibody according to claim 1 , wherein a mutation in the CH3m1 domain or the CH3m2 domain to form a structural hole is a change of a tyrosine residue to a threonine residue or a combination of a change of a threonine residue to a serine residue claim 1 , a change of a leucine residue to an alanine residue claim 1 , and a change of a tyrosine residue to a valine residue.7. The MAT-Fab antibody according to claim 6 , wherein the mutation to change a tyrosine residue to a threonine residue changes tyrosine at position 62 of the CH3 domain to threonine.8. The MAT-Fab antibody according to claim 6 , wherein the combination of a change of a threonine residue to a serine residue claim 6 , a change of a leucine residue to an alanine residue claim 6 , and a change of a tyrosine residue to a valine residue is a combination of a change of threonine at position 21 of the CH3 domain to ...

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo. 494-. (canceled)95. A binding protein having one or more amino acid conservative substitutions in the binding protein of any one of - , which has equivalent activity as the corresponding binding protein in - without the amino acid conservative substitutions.96. A pharmaceutical composition comprising the binding protein of any one of - and a pharmaceutically acceptable carrier.97. A method of treating or preventing a condition in a subject in need thereof claim 96 , the method comprising administering to the subject an effective amount of the pharmaceutical composition of .98. (canceled)99. The method of claim 97 , wherein the condition is an inflammatory disease claim 97 , autoimmune disease claim 97 , neurodegenerative disease claim 97 , cancer claim 97 , or spinal cord injury. This application is a United States national stage filing under 35 U.S.C. § 371 of International Application No. PCT/US2017/016691, filed Feb. 6, 2017, designating the U.S., which claims priority to International Application No. PCT/CN2016/073722, filed Feb. 6, 2016, the contents of which are incorporated herein by reference in their entireties.The present invention relates to multivalent and multispecific binding proteins, and to methods of making and using multivalent and multispecific binding proteins.The contents of the text file submitted electronically herewith are incorporated herein by reference in their entirety: A computer readable format copy of the Sequence Listing (filename: EPBI_002_01WO_SeqList_ST25.txt, date recorded: Feb. 3, 2017, file size 510 KB). ...

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo. 157.-. (canceled)58. A binding protein comprising at least two polypeptide chains , wherein the polypeptide chains pair to form IgG-like molecules capable of binding two or more antigens , wherein the first polypeptide chain comprises VL , CL , VH , and CH1 , wherein VL is a light chain variable domain , CL is a light chain constant domain , VH is a heavy chain variable domain , CH1 is the first constant domain of the heavy chain , A is a first antigen , and B is a second antigen.59. The binding protein of claim 58 , wherein the binding protein comprises three polypeptide chains claim 58 , wherein the second polypeptide chain comprises VHand CH1 claim 58 , and wherein the third polypeptide chain comprises VLand CL.60. The binding protein of claim 59 , wherein the first polypeptide chain comprises claim 59 , from amino to carboxyl terminus claim 59 , i) VL-CL-VH-CH1-Fc or ii) VH-CH1-VL-CL-Fc; the second polypeptide chain comprises claim 59 , from amino to carboxyl terminus claim 59 , VH-CH1 and the third polypeptide chain comprises claim 59 , from amino to carboxyl terminus claim 59 , VL-CL.61. The binding protein of claim 59 , wherein the binding protein comprises a first polypeptide chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 15 claim 59 , 25 claim 59 , 27 claim 59 , 41 claim 59 , 48 claim 59 , 87 claim 59 , or 92; a second polypeptide chain comprising an amino acid sequence according to SEQ ID NO: 21 claim 59 , 44 claim 59 , 89 claim 59 , or 95; and a third polypeptide chain comprising a sequence ...

FABS-IN-TANDEM IMMUNOGLOBULIN AND USES THEREOF

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo. 1. A binding protein comprising at least two polypeptide chains , wherein the polypeptide chains pair to form IgG-like molecules capable of binding two or more antigens , wherein the first polypeptide chain comprises VL , CL , VH , and CH1 , wherein VL is a light chain variable domain , CL is a light chain constant domain , VH is a heavy chain variable domain , CH1 is the first constant domain of the heavy chain , A is a first antigen , and B is a second antigen.2. The binding protein of claim 1 , wherein the binding protein comprises three polypeptide chains claim 1 , wherein the second polypeptide chain comprises VHand CH1 claim 1 , and wherein the third polypeptide chain comprises VLand CL.3. The binding protein of claim 2 , wherein the first polypeptide chain comprises claim 2 , from amino to carboxyl terminus claim 2 , i) VL-CL-VH-CH1-Fc or ii) VH-CH1-VL-CL-Fc; the second polypeptide chain comprises claim 2 , from amino to carboxyl terminus claim 2 , VH-CH1 and the third polypeptide chain comprises claim 2 , from amino to carboxyl terminus claim 2 , VL-CL.4. The binding protein of claim 2 , wherein the binding protein comprises a first polypeptide chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 15 claim 2 , 25 claim 2 , 27 claim 2 , 41 claim 2 , 48 claim 2 , 87 claim 2 , or 92; a second polypeptide chain comprising an amino acid sequence according to SEQ ID NO: 21 claim 2 , 44 claim 2 , 89 claim 2 , or 95; and a third polypeptide chain comprising a sequence according to SEQ ID NO: 23 claim 2 , 46 claim 2 ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 165-. (canceled)66. A method of producing a binding protein , comprising culturing a host cell in culture medium , wherein said host cell comprises:(a) a first nucleic acid encoding a first polypeptide chain of the binding protein that comprises formula 1: VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first heavy chain variable domain, VD2 is a second heavy chain variable domain, C is a heavy chain constant domain, X1 is a linker with the proviso that it is not CH1, X2 is an Fc region, and n is 0 or 1; and(b) a second nucleic acid encoding a second polypeptide chain of the binding protein that comprises formula 2: VD1-(X1)n-VD2-C, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a light chain constant domain, X1 is a linker with the proviso that it is not CH1, and n is 0 or 1;wherein the first nucleic acid is present on the same or a different expression vector as the second nucleic acid;wherein the culturing of the host cell is under conditions sufficient to produce the first and second polypeptide chains; andwherein one of the first polypeptide chain and one of the second polypeptide chain form a divalent form of the binding protein comprising two antigen binding sites, and wherein two of the first polypeptide chains and two of the second polypeptides form a tetravalent form of the binding protein comprising four antigen binding sites.67. The method of claim 66 , wherein 50%-75% of the binding protein produced is a dual specific tetravalent binding protein.68. The method of claim 66 , wherein 75%-90% of the binding protein produced is a dual specific tetravalent binding protein.69. The method of claim 66 , wherein 90%-95% of the binding protein produced is a dual specific tetravalent binding ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 151-. (canceled)52. An isolated nucleic acid encoding an amino acid sequence of at least one of two polypeptide chains that form a binding protein , wherein said at least one polypeptide chain is:(a) a first polypeptide chain of said binding protein that comprises formula 1: VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first heavy chain variable domain, VD2 is a second heavy chain variable domain, C is a heavy chain constant domain, X1 is a linker with the proviso that it is not CH1, X2 is an Fc region, and n is 0 or 1; or(b) a second polypeptide chain of said binding protein that comprises formula 2: VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a light chain constant domain, X1 is a linker with the proviso that it is not CH1, X2 does not comprise an Fc region, and n is 0 or 1;wherein said first polypeptide chain and said second polypeptide chain of said binding protein form two antigen binding sites.53. A vector comprising an isolated nucleic acid according to .54. The vector of wherein said vector is selected from the group consisting of pcDNA claim 53 , pTT claim 53 , pTT3 claim 53 , pEFBOS claim 53 , pBV claim 53 , pJV claim 53 , pcDNA3.1 TOPO claim 53 , pEF6 TOPO claim 53 , and pBJ.55. A host cell comprising a vector according to .56. The host cell according to claim 55 , wherein said host cell is a prokaryotic cell.57E. coli.. The host cell according to claim 56 , wherein said host cell is58. The host cell according to claim 55 , wherein said host cell is a eukaryotic cell.59. The host cell according to claim 58 , wherein said eukaryotic cell is selected from the group consisting of protist cell claim 58 , animal cell claim 58 , plant cell claim 58 , and ...

Dual Variable Domain Immunoglobulin and Uses Thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

INTERLEUKIN -13 BINDING PROTEINS

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental. 1. A recombinant anti-IL-13 antibody , or antigen-binding fragment thereof , wherein said recombinant anti-IL-13 antibody:binds human IL-13;comprises two variable domains, wherein one variable domain comprises the amino acid sequence of SEQ ID NO:80 and the other variable domain comprises the amino acid sequence of SEQ ID NO:81;comprises a human IgG1 heavy chain constant region comprising a hinge region comprising a leucine to alanine change at position 234 and a leucine to alanine change at position 235;comprises a human kappa light chain constant region;blocks IL-13 binding to IL-13Rα1 and to IL-13Rα2; andbinds a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue.2. The recombinant anti-IL-13 antibody claim 1 , or antigen-binding fragment thereof claim 1 , according to claim 1 , wherein said recombinant anti-IL-13 antibody claim 1 , or antigen-binding fragment thereof claim 1 , comprises four variable domains claim 1 , wherein each of two of the variable domains comprises the amino acid sequence of SEQ ID NO:80 and each of the other two of the variable domains comprises the amino acid sequence of SEQ ID NO:81.3. A pharmaceutical composition comprising a recombinant anti-IL-13 antibody claim 1 , or antigen-binding fragment thereof claim 1 , ...

IL-1 Binding Proteins

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions. 2. A binding protein comprising first and second polypeptide chains , wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n , wherein:VD1 is a first heavy chain variable domain;VD2 is a second heavy chain variable domain;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region; andn is independently 0 or 1; andwherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n,wherein:VD1 is a first light chain variable domain;VD2 is a second light chain variable domain;C is a light chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 does not comprise an Fc region; andn is independently 0 or 1;wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 213 and 227; and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 60-148, 196, 198, 200, 202, 204, 206, 208 and 210;wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 216 and 229; and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 149-189, 197, 199, 201, 203, 205, 207, 209 and 211; and wherein the binding protein binds human IL-1β and human IL-1α.330-. (canceled)31. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide chain amino acid sequence of the binding protein of .3245-. (canceled)46. A method for reducing human IL-1 activity comprising contacting a human IL-1 protein with the binding protein of such that human IL-1 protein activity is reduced.47. A method for reducing human IL-1 activity in a human subject ...

Dual variable domain immunoglobin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobin and uses thereof

IL-1 BINDING PROTEINS

REFERIDA A UNA PROTEINA DE UNION QUE COMPRENDE: A) UNA SECUENCIA DE AMINOACIDOS DE LA PORCION VARIABLE DE CADENA PESADA SELECCIONADA DE SEQ ID Nº 37, 38, 39, 40, 48, 50, 52, 54; B) UNA SECUENCIA DE AMINOACIDOS DE LA PORCION VARIABLE DE CADENA LIVIANA SELECCIONADA DE SEQ ID Nº 41, 42, 43, 44, 45, 46, 47, 49, 51, 53, 55. DICHA PROTEINA DE UNION TAMBIEN COMPRENDE UN AGENTE QUE SE SELECCIONA DEL GRUPO QUE CONSISTE EN UNA MOOECULA DE INMUNOADHESION, UN AGENTE PARA REALIZAR UN DIAGNOSTICO POR IMAGENES, UN AGENTE TERAPEUTICO Y UN AGENTE CITOTOXICO, DIENDO UTIL EN EL TRATAMIENTO DE ARTRITIS, OSTEOARTRIITS, COLITIS ULCEROSA, RECHAZO DE TRASPLANTE DE ORGANOS, ESTERILIDAD FEMEMNINA, ENTRE OTROS REFERRING TO A BINDING PROTEIN THAT INCLUDES: A) A SEQUENCE OF AMINO ACIDS OF THE VARIABLE PORTION OF HEAVY CHAIN SELECTED FROM SEQ ID No. 37, 38, 39, 40, 48, 50, 52, 54; B) AN AMINO ACID SEQUENCE OF THE SELECTED LIGHT CHAIN VARIABLE PORTION OF SEQ ID No. 41, 42, 43, 44, 45, 46, 47, 49, 51, 53, 55. SAID BINDING PROTEIN ALSO INCLUDES AN AGENT THAT IS SELECTED FROM THE GROUP THAT CONSISTS OF AN IMMUNOADHESION MOOECULA, AN AGENT TO PERFORM A DIAGNOSIS BY IMAGES, A THERAPEUTIC AGENT AND A CYTOTOXIC AGENT, USEFUL IN THE TREATMENT OF ARTHRITIS, OSTEOARTISHATERUS RECYCLES, COLITITIS, FATALOSHYTHERS RECITES AMONG OTHERS

Il-1 -alpha and -beta bispecific dual variable domain immunoglobulins and their use.

La presente invención se refiere a proteínas de enlace multivalentes y multiespecíficas genéticamente modificadas, métodos de producción, y específicamente a sus usos en la prevención, diagnóstico, y/o tratamiento de enfermedades.

Fabs-in-tandem immunoglobulin and uses thereof.

La presente invencion proporciona proteinas de enlace multivalentes y multiespecificas que son capaces de enlazarse a dos o mas antigenos o dos o mas epitopos. La presente invencion tambien proporciona metodos para hacer y usar dichas proteinas de enlace multivalentes y multiespecificas, incluyendo metodos para usar dichas proteinas de enlace para la prevencion o el tratamiento de diversas enfermedades, o para detectar antigenos especificos in vitro o in vivo.

Efficiently expressed egfr and pd-l1 bispecific binding proteins

Bispecific Fabs-In-Tandem Immunoglobulin (FTT-Ig) binding proteins that bind both EGFR and PD-L1 simultaneously are disclosed. Such bispecific EGFR/PD-L1 FIT-Ig binding proteins are efficiently expressed and are useful for blocking EGFR signaling, for blocking PD-L1 signaling, and for treating cancer.

Fabs-in-tandem immunoglobulin and uses thereof

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

Il-1 binding proteins

The present invention describes IL-1α binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1α. Binding proteins of the invention have high affinity for IL-1α and neutralize IL-1α activity. A binding protein of the invention can be a full-length antibody or an IL-1α-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1α binding proteins of the invention are useful for detecting IL-1α and for inhibiting IL-1α activity, including in a human subject suffering from a disease or disorder in which IL-1α activity is detrimental.

Dual variable domain immunoglobulins and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Monovalent asymmetric tandem fab bispecific antibodies

The invention provides monovalent, asymmetric tandem Fab bispecific antibodies that can bind two epitopes or two antigens, compositions comprising such antibodies, uses of such antibodies, methods of making such antibodies, nucleic acids encoding such antibodies, and host cells comprising such nucleic acids.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Interleukin -13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Interleukin -13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Interleukin -13 binding proteins

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Dual variable domain immunoglobulins and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Dual variable domain immunoglobin and uses thereof

DUAL VARIABLE DOMAIN IMMUNOGLOBIN AND USES THEREOF The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Dual variable domain immunoglobin and uses thereof

DUAL VARIABLE DOMAIN IMMUNOGLOBIN AND USES THEREOF The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Monovalent asymmetric tandem fab bispecific antibodies

Dual variable domain immunoglobin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Antibodies to cd3 and bcma, and bispecific binding proteins made therefrom

High-affinity antibodies recognizing CD3 and B Cell Maturation Factor protein (BCMA) are Provided. Binding sites from humanized anti-CD3 and anti-BCMA antibodies are incorporated into a Fabs-in-Tandem Immunoglobulin format without significant loss of binding affinity, and the resultant bispecific, multivalent binding proteins are able to bind to both CD3 and BCMA simultaneously. Such antibodies, antigen-binding portions thereof, and bispecific FIT-Ig binding proteins are useful for treating cancer.

Interleukin-13 binding proteins

The present invention encompasses IL- 13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hlL-13 activity, e.g., in a human subject suffering from a disorder in which hTL-13 activity is detrimental.

Fabs-in-tandem immunoglobulin and uses thereof

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

Interleukin -13 binding proteins

Dual variable domain immunoglobulin and uses thereof

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Tri-variable domain binding proteins and uses thereof

The present invention provides engineered multivalent and multispecific binding proteins, as well as methods of making them. Methods for using the multivalent and multispecific binding proteins of the invention in the prevention, diagnosis, and/or treatment of disease are also provided.

Fabs-in-tandem immunoglobulin and uses thereof

Anti-ror1 antibodies and related bispecific binding proteins

Provided herein are antibodies recognizing receptor tyrosine kinase-like orphan receptor 1 (ROR1), bispecific ROR1/CD3 binding proteins such as FIT-Ig and MAT-Fab binding proteins, and the use of the antibodies and bispecific binding proteins for treating hematopoietic cancers and solid tumors.

UNION PROTEINS WITH TRIVARIABLE DOMAINS AND ITS USES

Proteínas de unión multivalentes y multiespecíficas, y métodos para elaborarlas. También se proveen métodos para usar las proteínas de unión multivalentes y multiespecíficas de la invención en la prevención, el diagnóstico y/o el tratamiento de enfermedades.

Il-1 binding proteins

The present invention encompasses IL-1α binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1α and neutralize IL-1α activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1α and for inhibiting IL-1α activity, e.g., in a human subject suffering from a disorder in which IL-1α activity is detrimental.

Interleukin -13 binding proteins.

La presente invención comprende proteínas de enlace lL 13. Específicamente la presente invención se refiere a anticuerpos que son anticuerpos quiméricos, injertados con CDR y humanizados. Los anticuerpos preferidos tienen alta afinidad para hlL-13 y neutralizan la actividad hlL-13 in vitro e in vivo. Un anticuerpo de la presente invención puede ser un anticuerpo de longitud total o una parte de enlace de antígeno el mismo. También se proporciona un método para utilizar los anticuerpos de la presente invención. Los anticuerpos o partes de anticuerpo de la presente invención son útiles para detectar hlL-13 o para inhibir la actividad de hlL-13, por ejemplo en un sujeto humano que padece de un trastorno en el cual la actividad de hTL-13 es perjudicial.

Interleukin- 13 binding proteins

Il-1 binding proteins

A binding protein comprising an antigen binding domain, said binding protein capable of binding human IL-1β, said antigen binding domain comprising six CDRs: CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below: CDR-H1: X1–Y–D–M–S (SEQ ID NO:190), wherein; X1 is K or R; CDR-H2: Y–X2–S–X4–G–G–X7–G–T–Y–Y–P–D–X14–X15–K–G (SEQ ID NO:191), wherein; X2 is I or V; X4 is S or H; X7 is G or A; X14 is T or S; and X15 is V or A; CDR-H3: G–G–V–X4–K–G–X7–F–D–X10 (SEQ ID NO:192), wherein; X4 is T or Y; X7 is Y or C; and X10 is V, E, L, M, Q, or Y; CDR-L1: R–A–S–G–N–I–X7–X8–X9–L–X11 (SEQ ID NO:193), wherein; X7 is H, Y, or W; X8 is N, G, T, Q, E, H, D, or K; X9 is Y or W; and X11 is T, A, or N; CDR-L2: X1–A–K–X4–L–X6–X7 (SEQ ID NO:194), wherein; X1 is N, Q, or D; X4 is T, N, I, E, or S; X6 is A, M, or E; and X7 is D, E, S, or A; and CDR-L3: Q–X2–F–W–X5–X6–P–X8–X9 (SEQ ID NO:195), wherein; X2 is H or Q; X5 is S, N, T, K, R, or M; X6 is I or L; X8 is Y or A; and X9 is T, I, and N except that CDR-H2 cannot be Y-I-S-S-G-G-G-G-T-Y-Y-P-D-T-V-K-G (SEQ ID NO:18); CDR-H3 cannot be G-G-V-T-K-G-Y-F-D-V (SEQ ID NO:19); CDR-L1 cannot be R-A-S-G-N-I-H-N-Y-L-T (SEQ ID NO:20); CDR-L2 cannot be N-A-K-T-L-A-D (SEQ ID NO:21); and CDR-L3 cannot be Q-H-F-W-S-I-P-Y-T (SEQ ID NO:22).

Bispecific dual variable domain immunoglobulins of il-1 alpha and beta and their use

La presente invención se refiere a proteínas de enlace multivalentes y multiespecíficas diseñadas, métodos de producción, y específicamente a sus usos en la prevención, diagnóstico y/o tratamiento de enfermedades. The present invention relates to multivalent and multispecific designed binding proteins, production methods, and specifically their uses in the prevention, diagnosis and / or treatment of diseases.

Il-1 binding proteins

Proteins that bind IL-1alpha and IL-1beta are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1alpha and IL-1beta in cells, tissues, samples, and compositions.

IMMUNOGLOBULIN WITH FABS IN TANDEM

<p>La presente invención proporciona proteínas de enlace multivalentes y multiespecíficas que son capaces de enlazarse a dos o más antígenos o dos o más epítopos. Particularmente,  la presente invención se refiere a una proteína de unión multiespecífica y multivalente que comprende al menos  tres cadenas de polipéptidos. Adicionalmente, la presente invención se refiere a una composición farnmacéutica que comprende la proteína de unión multiespecífica y multivalente y uno o más portadores farmacéuticamente aceptables.</p> <p> The present invention provides multivalent and multispecific binding proteins that are capable of binding to two or more antigens or two or more epitopes. Particularly, the present invention relates to a multispecific and multivalent binding protein that comprises at least three polypeptide chains. Additionally, the present invention relates to a pharmaceutical composition comprising multispecific and multivalent binding protein and one or more pharmaceutically acceptable carriers. </p>

PROTEINS OF UNION TO INTERLEUQUINA-13

La presente invención se relaciona con proteínas de unión a IL-13 y, específicamente, con su uso en la prevención y/o el tratamiento de diversas enfermedades incluyendo asma, alergias, COPD, fibrosis y cáncer.

DUAL VARIABLE DOMAIN IMMUNOGLOBULIN (DVD-lg)

il-13 binding proteins, recombinant anti-il-13 antibody, antibody construct, pharmaceutical compositions and uses thereof to reduce il-13 biological activity and function and treat respiratory disorders

PROTEÍNAS LIGANTES A INTERLEUCINA-13, ANTICORPO ISOLADO, CONSTRUTO E CONJUGADO ANTICORPO, ÁCIDO NUCLÉICO ISOLADO, VETOR CÉLULA HOSPEDEIRA, MÉTODO PARA PRODUZIR PROTEÍNA LIGANTE, COMPOSIÇÃO E USO. A presente invenção abrange proteínas ligantes a IL-13. Especificamente, a invenção está relacionada a anticorpos que são quiméricos, enxertados de CDR e anticorpos humanizados. Os anticorpos preferidos têm alta afinidade para hIL-13 e neutralizam a atividade da hIL-13 in e in vivo anticorpo da invenção pode ser um anticorpo de comprimento completo ou uma sua parte antígeno-ligante. Método de produzir e o método de utilizar os anticorpos da invenção são também providos. Os anticorpos, ou porção anticorpos, da invenção são úteis para detectar hIL-13 e para inibir a ativ da hIL- 13 atividade, por exemplo, em um individuo humano que sofre de um distúrbio em que a atividade da hIL-13 é prejudicial. INTERLEUKIN-13 BINDING PROTEINS, ISOLATED ANTIBODY, ANTIBODY CONSTRUCT AND CONJUGATE, ISOLATED NUCLEIC ACID, HOST CELL VECTOR, METHOD FOR PRODUCING BINDING PROTEIN, COMPOSITION AND USE. The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR-grafted, and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in and in vivo. The antibody of the invention may be a full-length antibody or an antigen-ligand portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portion, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, for example, in a human subject suffering from a disorder in which hIL-13 activity is deleterious.

IL-1 UNION PROTEINS

La presente invención abarca proteínas de unión a IL-1a. Específicamente, la invención se relaciona con anticuerpos que son anticuerpos quiméricos, de CDR injertada y humanizados. Los anticuerpos de la invención tienen alta afinidad por IL-1a y neutralizan la actividad de IL-1a. Un anticuerpo de la invención puede ser un anticuerpo de longitud total o una porción de unión a antígeno del mismo. También se provee el método para preparar y el método para usar los anticuerpos de la invención. Los anticuerpos, o porciones de anticuerpo de la invención son útiles para detectar una IL-1a y para inhibir la actividad de IL-1a, p.e., en un sujeto humano que sufre de un trastorno en el cual la actividad de IL-1a es perjudicial. The present invention encompasses IL-1a binding proteins. Specifically, the invention relates to antibodies that are chimeric, grafted and humanized CDR antibodies. The antibodies of the invention have high affinity for IL-1a and neutralize the activity of IL-1a. An antibody of the invention may be a full length antibody or an antigen binding portion thereof. The method for preparing and the method for using the antibodies of the invention are also provided. The antibodies, or antibody portions of the invention are useful for detecting an IL-1a and for inhibiting the activity of IL-1a, eg, in a human subject suffering from a disorder in which the activity of IL-1a is detrimental. .

Dual variable domain immunoglobin and uses thereof