Immunobinders directed against sclerostin

Abstract

Proteins that bind sclerostin or sclerostin and TNF are described along with there use in composition and methods for treating, preventing, and diagnosing sclerostin related diseases and for detecting sclerostin or sclerostin and TNF in cells, tissues, samples, and compositions.

1 - 12 . (canceled) 
     
     
         13 . An isolated nucleic acid encoding a binding protein comprising an antigen binding domain capable of binding human sclerostin, the antigen binding domain comprising at least one CDR comprising an amino acid consensus, wherein the at least one CDR comprises an amino acid sequence selected from the group consisting of residues 31-35 of SEQ ID NO: 3; residues 50-66 of SEQ ID NO: 3; residues 99-108 of SEQ ID NO:3; residues 23-34 of SEQ ID NO: 4; residues 51-57 of SEQ ID NO: 4; residues 90-101 of SEQ ID NO:4; residues 31-35 of SEQ ID NO: 5; residues 50-66 of SEQ ID NO: 5; residues 99-115 of SEQ ID NO:5; residues 23-33 of SEQ ID NO: 6; residues 49-55 of SEQ ID NO: 6; residues 88-96 of SEQ ID NO:6; residues 31-35 of SEQ ID NO: 7; residues 50-66 of SEQ ID NO: 7; residues 99-107 of SEQ ID NO:7; residues 23-33 of SEQ ID NO: 8; residues 49-55 of SEQ ID NO: 8; residues 88-95 of SEQ ID NO:8; residues 31-35 of SEQ ID NO: 9; residues 50-66 of SEQ ID NO: 9; residues 99-107 of SEQ ID NO:9; residues 24-39 of SEQ ID NO: 10; residues 55-61 of SEQ ID NO: 10; residues 94-112 of SEQ ID NO:10; residues 31-35 of SEQ ID NO: 11; residues 50-66 of SEQ ID NO: 11; residues 99-111 of SEQ ID NO: 11; residues 24-39 of SEQ ID NO: 12; residues 55-61 of SEQ ID NO: 12; residues 94-113 of SEQ ID NO:12; residues 31-37 of SEQ ID NO: 13; residues 52-69 of SEQ ID NO: 13; residues 102-122 of SEQ ID NO:13; residues 24-34 of SEQ ID NO: 14; residues 50-56 of SEQ ID NO: 14; residues 89-97 of SEQ ID NO:14; Residues 31-35 of SEQ ID NO:1998; Residues 50-66 of SEQ ID NO:1998; Residues 99-110 of SEQ ID NO:1998; Residues 31-35 of SEQ ID NO.:1999; Residues 50-66 of SEQ ID NO.:1999; Residues 99-110 of SEQ ID NO.:1999; Residues 31-35 of SEQ ID NO.:2000; Residues 50-66 of SEQ ID NO.:2000; Residues 99-110 of SEQ ID NO.:2000; Residues 31-35 of SEQ ID NO.:2001; Residues 50-66 of SEQ ID NO.:2001; Residues 99-110 of SEQ ID NO.:2001; Residues 31-35 of SEQ ID NO.:2002; Residues 50-66 of SEQ ID NO.:2002; Residues 99-110 of SEQ ID NO.:2002; Residues 31-35 of SEQ ID NO.:2003; Residues 50-66 of SEQ ID NO.:2003; Residues 99-110 of SEQ ID NO.:2003; Residues 31-35 of SEQ ID NO.:2004; Residues 50-66 of SEQ ID NO.:2004; Residues 99-110 of SEQ ID NO.:2004; Residues 31-35 of SEQ ID NO.:2005; Residues 50-66 of SEQ ID NO.:2005; Residues 99-110 of SEQ ID NO.:2005; Residues 31-35 of SEQ ID NO.:2006; Residues 50-66 of SEQ ID NO.:2006; Residues 99-110 of SEQ ID NO.:2006; Residues 31-35 of SEQ ID NO.:2007; Residues 50-66 of SEQ ID NO.:2007; Residues 99-110 of SEQ ID NO.:2007; Residues 23-36 of SEQ ID NO.:2008; Residues 52-58 of SEQ ID NO.:2008; Residues 101-109 of SEQ ID NO.:2008; Residues 23-36 of SEQ ID NO.:2009; Residues 52-58 of SEQ ID NO.:2009; Residues 101-109 of SEQ ID NO.:2009; Residues 23-36 of SEQ ID NO.:2008; Residues 52-58 of SEQ ID NO.:2010; Residues 101-109 of SEQ ID NO.:2010; Residues 23-36 of SEQ ID NO.:2011; Residues 52-58 of SEQ ID NO.:2011; Residues 101-109 of SEQ ID NO.:2011; Residues 23-36 of SEQ ID NO.:2012; Residues 52-58 of SEQ ID NO.:2012; Residues 101-109 of SEQ ID NO.:2012; Residues 23-36 of SEQ ID NO.:2013; Residues 52-58 of SEQ ID NO.:2013; Residues 101-109 of SEQ ID NO.:2013; Residues 23-36 of SEQ ID NO.:2014; Residues 52-58 of SEQ ID NO.:2014; Residues 101-109 of SEQ ID NO.:2014; Residues 23-36 of SEQ ID NO.:2015; Residues 52-58 of SEQ ID NO.:2015; Residues 101-109 of SEQ ID NO.:2015; Residues 23-36 of SEQ ID NO.:2016; Residues 52-58 of SEQ ID NO.:2016; Residues 101-109 of SEQ ID NO.:2016; Residues 23-36 of SEQ ID NO.:2017; Residues 52-58 of SEQ ID NO.:2017; Residues 101-109 of SEQ ID NO.:2017; Residues 31-35 of SEQ ID NO:2020; Residues 50-66 of SEQ ID NO:2020; Residues 99-108 of SEQ ID NO:2020; Residues 31-35 of SEQ ID NO:2021; Residues 50-66 of SEQ ID NO:2021; Residues 99-108 of SEQ ID NO:2021; Residues 31-35 of SEQ ID NO:2022; Residues 50-66 of SEQ ID NO:2022; Residues 99-108 of SEQ ID NO:2022; Residues 31-35 of SEQ ID NO:2023; Residues 50-66 of SEQ ID NO:2023; Residues 99-108 of SEQ ID NO:2023; Residues 31-35 of SEQ ID NO:2024; Residues 50-66 of SEQ ID NO:2024; Residues 99-108 of SEQ ID NO:2024; Residues 31-35 of SEQ ID NO:2025; Residues 50-66 of SEQ ID NO:2025; Residues 99-108 of SEQ ID NO:2025; Residues 31-35 of SEQ ID NO:2026; Residues 50-66 of SEQ ID NO:2026; Residues 99-108 of SEQ ID NO:2026; Residues 31-35 of SEQ ID NO:2027; Residues 50-66 of SEQ ID NO:2027; Residues 99-108 of SEQ ID NO:2027; Residues 31-35 of SEQ ID NO:2028; Residues 50-66 of SEQ ID NO:2028; Residues 99-108 of SEQ ID NO:2028; Residues 31-35 of SEQ ID NO:2029; Residues 50-66 of SEQ ID NO:2029; Residues 99-108 of SEQ ID NO:2029; Residues 31-35 of SEQ ID NO:2030; Residues 50-66 of SEQ ID NO:2030; Residues 99-108 of SEQ ID NO:2030; Residues 31-35 of SEQ ID NO:2031; Residues 50-66 of SEQ ID NO:2031; Residues 99-108 of SEQ ID NO:2031; Residues 31-35 of SEQ ID NO:2032; Residues 50-66 of SEQ ID NO:2032; Residues 99-108 of SEQ ID NO:2032; Residues 31-35 of SEQ ID NO:2033; Residues 50-66 of SEQ ID NO:2033; Residues 99-108 of SEQ ID NO:2033; Residues 31-35 of SEQ ID NO:2034; Residues 50-66 of SEQ ID NO:2034; Residues 99-110 of SEQ ID NO:2034; Residues 31-35 of SEQ ID NO.:2035; Residues 51-57 of SEQ ID NO.:2035; Residues 90-101 of SEQ ID NO.:2035; Residues 31-35 of SEQ ID NO.:2036; Residues 51-57 of SEQ ID NO.:2036; Residues 90-101 of SEQ ID NO.:2036; Residues 31-35 of SEQ ID NO.:2037; Residues 51-57 of SEQ ID NO.:2035; Residues 90-101 of SEQ ID NO.:2037; Residues 31-35 of SEQ ID NO.:2038; Residues 51-57 of SEQ ID NO.:2038; Residues 90-101 of SEQ ID NO.:2038; Residues 31-35 of SEQ ID NO.:2039; Residues 51-57 of SEQ ID NO.:2039; Residues 90-101 of SEQ ID NO.:2039; Residues 31-35 of SEQ ID NO.:2040; Residues 51-57 of SEQ ID NO.:2040; Residues 90-101 of SEQ ID NO.:2040; Residues 31-35 of SEQ ID NO.:2041; Residues 51-57 of SEQ ID NO.:2041; Residues 90-101 of SEQ ID NO.:2041; Residues 31-35 of SEQ ID NO.:2042; Residues 51-57 of SEQ ID NO.:2042; Residues 90-101 of SEQ ID NO.:2042; Residues 31-35 of SEQ ID NO.:2043; Residues 51-57 of SEQ ID NO.:2043; Residues 90-101 of SEQ ID NO.:2043; Residues 31-35 of SEQ ID NO.:2044; Residues 51-57 of SEQ ID NO.:2044; Residues 90-101 of SEQ ID NO.:2044; Residues 31-35 of SEQ ID NO.:2045; Residues 51-57 of SEQ ID NO.:2045; Residues 90-101 of SEQ ID NO.:2045; Residues 31-35 of SEQ ID NO.:2046; Residues 51-57 of SEQ ID NO.:2046; Residues 90-101 of SEQ ID NO.:2046; Residues 31-35 of SEQ ID NO.:2047; Residues 51-57 of SEQ ID NO.:2047; Residues 90-101 of SEQ ID NO.:2047; Residues 31-35 of SEQ ID NO.:2048; Residues 51-57 of SEQ ID NO.:2048; Residues 90-101 of SEQ ID NO.:2048; Residues 31-35 of SEQ ID NO.:2049; Residues 51-57 of SEQ ID NO.:2049; and Residues 90-101 of SEQ ID NO.:2049. 
     
     
         14 . A vector comprising the isolated nucleic acid of  claim 13 . 
     
     
         15 . A host cell comprising the vector of  claim 15 . 
     
     
         16 . A method of producing a protein capable of binding sclerostin, comprising culturing the host cell of  claim 16  in culture medium under conditions sufficient to produce a binding protein capable of binding sclerostin. 
     
     
         17 - 23 . (canceled) 
     
     
         24 . A method for treating a subject for a disease or a disorder in which sclerostin activity is detrimental by administering to the subject a binding protein such that treatment is achieved, wherein the binding protein comprises an antigen binding domain capable of binding human sclerostin, the antigen binding domain comprising at least one CDR comprising an amino acid consensus wherein the at least one CDR comprises an amino acid sequence selected from the group consisting of residues 31-35 of SEQ ID NO: 3; residues 50-66 of SEQ ID NO: 3; residues 99-108 of SEQ ID NO:3; residues 23-34 of SEQ ID NO: 4; residues 51-57 of SEQ ID NO: 4; residues 90-101 of SEQ ID NO:4; residues 31-35 of SEQ ID NO: 5; residues 50-66 of SEQ ID NO: 5; residues 99-115 of SEQ ID NO:5; residues 23-33 of SEQ ID NO: 6; residues 49-55 of SEQ ID NO: 6; residues 88-96 of SEQ ID NO:6; residues 31-35 of SEQ ID NO: 7; residues 50-66 of SEQ ID NO: 7; residues 99-107 of SEQ ID NO:7; residues 23-33 of SEQ ID NO: 8; residues 49-55 of SEQ ID NO: 8; residues 88-95 of SEQ ID NO:8; residues 31-35 of SEQ ID NO: 9; residues 50-66 of SEQ ID NO: 9; residues 99-107 of SEQ ID NO:9; residues 24-39 of SEQ ID NO: 10; residues 55-61 of SEQ ID NO: 10; residues 94-112 of SEQ ID NO:10; residues 31-35 of SEQ ID NO: 11; residues 50-66 of SEQ ID NO: 11; residues 99-111 of SEQ ID NO: 11; residues 24-39 of SEQ ID NO: 12; residues 55-61 of SEQ ID NO: 12; residues 94-113 of SEQ ID NO:12; residues 31-37 of SEQ ID NO: 13; residues 52-69 of SEQ ID NO: 13; residues 102-122 of SEQ ID NO:13; residues 24-34 of SEQ ID NO: 14; residues 50-56 of SEQ ID NO: 14; residues 89-97 of SEQ ID NO:14; Residues 31-35 of SEQ ID NO:1998; Residues 50-66 of SEQ ID NO:1998; Residues 99-110 of SEQ ID NO:1998; Residues 31-35 of SEQ ID NO.:1999; Residues 50-66 of SEQ ID NO.:1999; Residues 99-110 of SEQ ID NO.:1999; Residues 31-35 of SEQ ID NO.:2000; Residues 50-66 of SEQ ID NO.:2000; Residues 99-110 of SEQ ID NO.:2000; Residues 31-35 of SEQ ID NO.:2001; Residues 50-66 of SEQ ID NO.:2001; Residues 99-110 of SEQ ID NO.:2001; Residues 31-35 of SEQ ID NO.:2002; Residues 50-66 of SEQ ID NO.:2002; Residues 99-110 of SEQ ID NO.:2002; Residues 31-35 of SEQ ID NO.:2003; Residues 50-66 of SEQ ID NO.:2003; Residues 99-110 of SEQ ID NO.:2003; Residues 31-35 of SEQ ID NO.:2004; Residues 50-66 of SEQ ID NO.:2004; Residues 99-110 of SEQ ID NO.:2004; Residues 31-35 of SEQ ID NO.:2005; Residues 50-66 of SEQ ID NO.:2005; Residues 99-110 of SEQ ID NO.:2005; Residues 31-35 of SEQ ID NO.:2006; Residues 50-66 of SEQ ID NO.:2006; Residues 99-110 of SEQ ID NO.:2006; Residues 31-35 of SEQ ID NO.:2007; Residues 50-66 of SEQ ID NO.:2007; Residues 99-110 of SEQ ID NO.:2007; Residues 23-36 of SEQ ID NO.:2008; Residues 52-58 of SEQ ID NO.:2008; Residues 101-109 of SEQ ID NO.:2008; Residues 23-36 of SEQ ID NO.:2009; Residues 52-58 of SEQ ID NO.:2009; Residues 101-109 of SEQ ID NO.:2009; Residues 23-36 of SEQ ID NO.:2008; Residues 52-58 of SEQ ID NO.:2010; Residues 101-109 of SEQ ID NO.:2010; Residues 23-36 of SEQ ID NO.:2011; Residues 52-58 of SEQ ID NO.:2011; Residues 101-109 of SEQ ID NO.:2011; Residues 23-36 of SEQ ID NO.:2012; Residues 52-58 of SEQ ID NO.:2012; Residues 101-109 of SEQ ID NO.:2012; Residues 23-36 of SEQ ID NO.:2013; Residues 52-58 of SEQ ID NO.:2013; Residues 101-109 of SEQ ID NO.:2013; Residues 23-36 of SEQ ID NO.:2014; Residues 52-58 of SEQ ID NO.:2014; Residues 101-109 of SEQ ID NO.:2014; Residues 23-36 of SEQ ID NO.:2015; Residues 52-58 of SEQ ID NO.:2015; Residues 101-109 of SEQ ID NO.:2015; Residues 23-36 of SEQ ID NO.:2016; Residues 52-58 of SEQ ID NO.:2016; Residues 101-109 of SEQ ID NO.:2016; Residues 23-36 of SEQ ID NO.:2017; Residues 52-58 of SEQ ID NO.:2017; Residues 101-109 of SEQ ID NO.:2017; Residues 31-35 of SEQ ID NO:2020; Residues 50-66 of SEQ ID NO:2020; Residues 99-108 of SEQ ID NO:2020; Residues 31-35 of SEQ ID NO:2021; Residues 50-66 of SEQ ID NO:2021; Residues 99-108 of SEQ ID NO:2021; Residues 31-35 of SEQ ID NO:2022; Residues 50-66 of SEQ ID NO:2022; Residues 99-108 of SEQ ID NO:2022; Residues 31-35 of SEQ ID NO:2023; Residues 50-66 of SEQ ID NO:2023; Residues 99-108 of SEQ ID NO:2023; Residues 31-35 of SEQ ID NO:2024; Residues 50-66 of SEQ ID NO:2024; Residues 99-108 of SEQ ID NO:2024; Residues 31-35 of SEQ ID NO:2025; Residues 50-66 of SEQ ID NO:2025; Residues 99-108 of SEQ ID NO:2025; Residues 31-35 of SEQ ID NO:2026; Residues 50-66 of SEQ ID NO:2026; Residues 99-108 of SEQ ID NO:2026; Residues 31-35 of SEQ ID NO:2027; Residues 50-66 of SEQ ID NO:2027; Residues 99-108 of SEQ ID NO:2027; Residues 31-35 of SEQ ID NO:2028; Residues 50-66 of SEQ ID NO:2028; Residues 99-108 of SEQ ID NO:2028; Residues 31-35 of SEQ ID NO:2029; Residues 50-66 of SEQ ID NO:2029; Residues 99-108 of SEQ ID NO:2029; Residues 31-35 of SEQ ID NO:2030; Residues 50-66 of SEQ ID NO:2030; Residues 99-108 of SEQ ID NO:2030; Residues 31-35 of SEQ ID NO:2031; Residues 50-66 of SEQ ID NO:2031; Residues 99-108 of SEQ ID NO:2031; Residues 31-35 of SEQ ID NO:2032; Residues 50-66 of SEQ ID NO:2032; Residues 99-108 of SEQ ID NO:2032; Residues 31-35 of SEQ ID NO:2033; Residues 50-66 of SEQ ID NO:2033; Residues 99-108 of SEQ ID NO:2033; Residues 31-35 of SEQ ID NO:2034; Residues 50-66 of SEQ ID NO:2034; Residues 99-110 of SEQ ID NO:2034; Residues 31-35 of SEQ ID NO.:2035; Residues 51-57 of SEQ ID NO.:2035; Residues 90-101 of SEQ ID NO.:2035; Residues 31-35 of SEQ ID NO.:2036; Residues 51-57 of SEQ ID NO.:2036; Residues 90-101 of SEQ ID NO.:2036; Residues 31-35 of SEQ ID NO.:2037; Residues 51-57 of SEQ ID NO.:2035; Residues 90-101 of SEQ ID NO.:2037; Residues 31-35 of SEQ ID NO.:2038; Residues 51-57 of SEQ ID NO.:2038; Residues 90-101 of SEQ ID NO.:2038; Residues 31-35 of SEQ ID NO.:2039; Residues 51-57 of SEQ ID NO.:2039; Residues 90-101 of SEQ ID NO.:2039; Residues 31-35 of SEQ ID NO.:2040; Residues 51-57 of SEQ ID NO.:2040; Residues 90-101 of SEQ ID NO.:2040; Residues 31-35 of SEQ ID NO.:2041; Residues 51-57 of SEQ ID NO.:2041; Residues 90-101 of SEQ ID NO.:2041; Residues 31-35 of SEQ ID NO.:2042; Residues 51-57 of SEQ ID NO.:2042; Residues 90-101 of SEQ ID NO.:2042; Residues 31-35 of SEQ ID NO.:2043; Residues 51-57 of SEQ ID NO.:2043; Residues 90-101 of SEQ ID NO.:2043; Residues 31-35 of SEQ ID NO.:2044; Residues 51-57 of SEQ ID NO.:2044; Residues 90-101 of SEQ ID NO.:2044; Residues 31-35 of SEQ ID NO.:2045; Residues 51-57 of SEQ ID NO.:2045; Residues 90-101 of SEQ ID NO.:2045; Residues 31-35 of SEQ ID NO.:2046; Residues 51-57 of SEQ ID NO.:2046; Residues 90-101 of SEQ ID NO.:2046; Residues 31-35 of SEQ ID NO.:2047; Residues 51-57 of SEQ ID NO.:2047; Residues 90-101 of SEQ ID NO.:2047; Residues 31-35 of SEQ ID NO.:2048; Residues 51-57 of SEQ ID NO.:2048; Residues 90-101 of SEQ ID NO.:2048; Residues 31-35 of SEQ ID NO.:2049; Residues 51-57 of SEQ ID NO.:2049; and Residues 90-101 of SEQ ID NO.:2049. 
     
     
         25 . The method of  claim 24 , wherein the disorder is selected from the group consisting of a respiratory disorder; asthma; allergic and nonallergic asthma; asthma due to infection; asthma due to infection with respiratory syncytial virus (RSV); chronic obstructive pulmonary disease (COPD); a condition involving airway inflammation; eosinophilia; fibrosis and/or excess mucus production; cystic fibrosis; pulmonary fibrosis; an atopic disorder; atopic dermatitis; urticaria; eczema; allergic rhinitis; allergic enterogastritis; an inflammatory and/or autoimmune condition of the skin; an inflammatory and/or autoimmune condition of gastrointestinal organs; inflammatory bowel disease (IBD); ulcerative colitis; Crohn's disease; an inflammatory and/or autoimmune condition of the liver; liver cirrhosis; liver fibrosis; liver fibrosis caused by hepatitis B and/or C virus; scleroderma; a tumors; a cancer; hepatocellular carcinoma; glioblastoma; lymphoma; Hodgkin's lymphoma; a viral infection; HTLV-1 infection (e.g., from HTLV-1); a suppression of expression of protective type 1 immune response, and a suppression of expression of protective type 1 immune responses during vaccination. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . A binding protein comprising first and second polypeptide chains, wherein the 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 first linker;   X2 is an Fc region;   (X1)n is (X1)0 or (X1)1;   (X2)n is (X2)0 or (X2)1; and   wherein the 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 second linker;   X2 does not comprise an Fc region;   (X1)n is (X1)0 or (X1)1;   (X2)n is (X2)0 or (X2)1; and   wherein the first and second X1 linker are the same or different;   wherein the first X1 linker is not CH1 and/or the second X1 linker is not CL and wherein   (a) the VD1 or VD2 heavy chain variable domain comprise three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, the VD1 or VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the binding protein is capable of binding sclerostin and another target;   (b) the VD1 and VD2 heavy chain variable domains independently comprise three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, the VD1 or VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the binding protein is capable of binding sclerostin and sclerostin;   (c) the VD1 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, and the VD2 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 292, 302, 312, 322, 332, 342, 352, 362, 372, 382, 392, 402, 412, 422, 432, 442, 452, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 562, 572, 582, 592, 602, 612, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, 882, 892, 902, 912, 922, 932, 942, 952, 962, 972, 982, 992, 1002, 1012, 1022, 1032, 1042, 1052, 1062, 1072, 1082, 1092, 1102, 1112, 1122, 1132, 1142, 1152, 1162, 1172, 1182, 1192, 1202, 1212, 1222, 1232, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1342, 1352, 1362, 1372, 1382, 1392, 1402, 1412, 1422, 1432, 1442, 1452, 1462, 1472, 1482, 1492, 1502, 1512, 1522, 1532, 1542, 1552, 1562, 1572, 1582, 1592, 1602, 1612, 1622, 1632, 1642, 1652, 1662, 1672, and 1682; the VD1 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147, 157, 167, 177, 187, 197, 207, 217, 227, 237, 247, 257, 267, 277, 287, 297, 307, 317, 327, 337, 347, 357, 367, 377, 387, 397, 407, 417, 427, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 767, 777, 787, 797, 807, 817, 827, 837, 847, 857, 867, 877, 887, 897, 907, 917, 927, 937, 947, 957, 967, 977, 987, 997, 1007, 1017, 1027, 1037, 1047, 1057, 1067, 1077, 1087, 1097, 1107, 1117, 1127, 1137, 1147, 1157, 1167, 1177, 1187, 1197, 1207, 1217, 1227, 1237, 1247, 1257, 1267, 1277, 1287, 1297, 1307, 1317, 1327, 1337, 1347, 1357, 1367, 1377, 1387, 1397, 1407, 1417, 1427, 1437, 1447, 1457, 1467, 1477, 1487, 1497, 1507, 1517, 1527, 1537, 1547, 1557, 1567, 1577, 1587, 1597, 1607, 1617, 1627, 1637, 1647, 1657, 1667, 1677, and 1687, and the binding protein is capable of binding sclerostin and TNF-α; or   (d) the VD2 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, and the VD1 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 292, 302, 312, 322, 332, 342, 352, 362, 372, 382, 392, 402, 412, 422, 432, 442, 452, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 562, 572, 582, 592, 602, 612, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, 882, 892, 902, 912, 922, 932, 942, 952, 962, 972, 982, 992, 1002, 1012, 1022, 1032, 1042, 1052, 1062, 1072, 1082, 1092, 1102, 1112, 1122, 1132, 1142, 1152, 1162, 1172, 1182, 1192, 1202, 1212, 1222, 1232, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1342, 1352, 1362, 1372, 1382, 1392, 1402, 1412, 1422, 1432, 1442, 1452, 1462, 1472, 1482, 1492, 1502, 1512, 1522, 1532, 1542, 1552, 1562, 1572, 1582, 1592, 1602, 1612, 1622, 1632, 1642, 1652, 1662, 1672, and 1682; the VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the VD1 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147, 157, 167, 177, 187, 197, 207, 217, 227, 237, 247, 257, 267, 277, 287, 297, 307, 317, 327, 337, 347, 357, 367, 377, 387, 397, 407, 417, 427, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 767, 777, 787, 797, 807, 817, 827, 837, 847, 857, 867, 877, 887, 897, 907, 917, 927, 937, 947, 957, 967, 977, 987, 997, 1007, 1017, 1027, 1037, 1047, 1057, 1067, 1077, 1087, 1097, 1107, 1117, 1127, 1137, 1147, 1157, 1167, 1177, 1187, 1197, 1207, 1217, 1227, 1237, 1247, 1257, 1267, 1277, 1287, 1297, 1307, 1317, 1327, 1337, 1347, 1357, 1367, 1377, 1387, 1397, 1407, 1417, 1427, 1437, 1447, 1457, 1467, 1477, 1487, 1497, 1507, 1517, 1527, 1537, 1547, 1557, 1567, 1577, 1587, 1597, 1607, 1617, 1627, 1637, 1647, 1657, 1667, 1677, and 1687, and the binding protein is capable of binding TNF-α, and sclerostin.   
     
     
         33 - 40 . (canceled) 
     
     
         41 . A binding protein capable of binding two antigens comprising four polypeptide chains, wherein two polypeptide chains comprise 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 first linker;   X2 is an Fc region;   (X1)n is (X1)0 or (X1)1;   (X2)n is (X2)0 or (X2)1; and   wherein two polypeptide chains comprise 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 second linker;   X2 does not comprise an Fc region;   (X1)n is (X1)0 or (X1)1;   (X2)n is (X2)0 or (X2)1; and   wherein the first and second X1 linker are the same or different;   wherein the first X1 linker is not CH1 and/or the second X1 linker is not CL and wherein   (a) the VD1 or VD2 heavy chain variable domain comprise three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, the VD1 or VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the binding protein is capable of binding sclerostin and another target;   (b) the VD1 and VD2 heavy chain variable domains independently comprise three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, the VD1 or VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the binding protein is capable of binding sclerostin and sclerostin;   (c) the VD1 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, and the VD2 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 292, 302, 312, 322, 332, 342, 352, 362, 372, 382, 392, 402, 412, 422, 432, 442, 452, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 562, 572, 582, 592, 602, 612, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, 882, 892, 902, 912, 922, 932, 942, 952, 962, 972, 982, 992, 1002, 1012, 1022, 1032, 1042, 1052, 1062, 1072, 1082, 1092, 1102, 1112, 1122, 1132, 1142, 1152, 1162, 1172, 1182, 1192, 1202, 1212, 1222, 1232, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1342, 1352, 1362, 1372, 1382, 1392, 1402, 1412, 1422, 1432, 1442, 1452, 1462, 1472, 1482, 1492, 1502, 1512, 1522, 1532, 1542, 1552, 1562, 1572, 1582, 1592, 1602, 1612, 1622, 1632, 1642, 1652, 1662, 1672, and 1682; the VD1 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147, 157, 167, 177, 187, 197, 207, 217, 227, 237, 247, 257, 267, 277, 287, 297, 307, 317, 327, 337, 347, 357, 367, 377, 387, 397, 407, 417, 427, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 767, 777, 787, 797, 807, 817, 827, 837, 847, 857, 867, 877, 887, 897, 907, 917, 927, 937, 947, 957, 967, 977, 987, 997, 1007, 1017, 1027, 1037, 1047, 1057, 1067, 1077, 1087, 1097, 1107, 1117, 1127, 1137, 1147, 1157, 1167, 1177, 1187, 1197, 1207, 1217, 1227, 1237, 1247, 1257, 1267, 1277, 1287, 1297, 1307, 1317, 1327, 1337, 1347, 1357, 1367, 1377, 1387, 1397, 1407, 1417, 1427, 1437, 1447, 1457, 1467, 1477, 1487, 1497, 1507, 1517, 1527, 1537, 1547, 1557, 1567, 1577, 1587, 1597, 1607, 1617, 1627, 1637, 1647, 1657, 1667, 1677, and 1687, and the binding protein is capable of binding sclerostin and TNF-α; or   (d) the VD2 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 634, 644, 654, 664, 674, 684, 694, 704, 714, 724, 734, 744, 754, 764, 774, 784, 794, 804, 814, 824, 834, 844, 854, 864, 874, 884, 894, 904, 914, 924, 934, 944, 954, 964, 974, 984, 994, 1004, 1014, 1024, 1034, 1044, 1054, 1064, 1074, 1084, 1094, 1114, 1124, 1134, 1144, 1154, 1164, 1174, 1184, 1194, 1204, 1214, 1224, 1234, 1244, 1254, 1264, 1274, 1284, 1294, 1304, 1314, 1324, 1334, 1344, 1354, 1364, 1374, 1384, 1394, 1404, 1414, 1424, 1434, 1444, 1454, 1464, 1474, 1484, 1494, 1504, 1514, 1524, 1534, 1544, 1554, 1564, 1574, 1584, 1594, 1604, 1614, 1624, 1634, 1644, 1654, 1664, 1674, and 1684, and the VD1 heavy chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 292, 302, 312, 322, 332, 342, 352, 362, 372, 382, 392, 402, 412, 422, 432, 442, 452, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 562, 572, 582, 592, 602, 612, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, 882, 892, 902, 912, 922, 932, 942, 952, 962, 972, 982, 992, 1002, 1012, 1022, 1032, 1042, 1052, 1062, 1072, 1082, 1092, 1102, 1112, 1122, 1132, 1142, 1152, 1162, 1172, 1182, 1192, 1202, 1212, 1222, 1232, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1242, 1252, 1262, 1272, 1282, 1292, 1302, 1312, 1322, 1332, 1342, 1352, 1362, 1372, 1382, 1392, 1402, 1412, 1422, 1432, 1442, 1452, 1462, 1472, 1482, 1492, 1502, 1512, 1522, 1532, 1542, 1552, 1562, 1572, 1582, 1592, 1602, 1612, 1622, 1632, 1642, 1652, 1662, 1672, and 1682; the VD2 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 629, 639, 649, 659, 669, 679, 689, 699, 709, 719, 729, 739, 749, 759, 769, 779, 789, 799, 809, 819, 829, 839, 849, 859, 869, 879, 889, 899, 909, 919, 929, 939, 949, 959, 969, 979, 989, 999, 1009, 1019, 1029, 1039, 1049, 1059, 1069, 1079, 1089, 1099, 1109, 1119, 1129, 1139, 1149, 1159, 1169, 1179, 1189, 1199, 1209, 1219, 1229, 1239, 1249, 1259, 1269, 1279, 1289, 1299, 1309, 1319, 1329, 1339, 1349, 1359, 1369, 1379, 1389, 1399, 1409, 1419, 1429, 1439, 1449, 1459, 1469, 1479. 1489, 1499, 1509, 1519, 1529, 1539, 1549, 1559, 1569, 1579, 1589, 1599, 1609, 1619, 1629, 1639, 1649, 1659, 1669, 1679, and 1689, and the VD1 light chain variable domain comprises three CDRs selected from the group consisting of SEQ ID NO: 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147, 157, 167, 177, 187, 197, 207, 217, 227, 237, 247, 257, 267, 277, 287, 297, 307, 317, 327, 337, 347, 357, 367, 377, 387, 397, 407, 417, 427, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 767, 777, 787, 797, 807, 817, 827, 837, 847, 857, 867, 877, 887, 897, 907, 917, 927, 937, 947, 957, 967, 977, 987, 997, 1007, 1017, 1027, 1037, 1047, 1057, 1067, 1077, 1087, 1097, 1107, 1117, 1127, 1137, 1147, 1157, 1167, 1177, 1187, 1197, 1207, 1217, 1227, 1237, 1247, 1257, 1267, 1277, 1287, 1297, 1307, 1317, 1327, 1337, 1347, 1357, 1367, 1377, 1387, 1397, 1407, 1417, 1427, 1437, 1447, 1457, 1467, 1477, 1487, 1497, 1507, 1517, 1527, 1537, 1547, 1557, 1567, 1577, 1587, 1597, 1607, 1617, 1627, 1637, 1647, 1657, 1667, 1677, and 1687, and the binding protein is capable of binding TNF-α and sclerostin.   
     
     
         42 - 44 . (canceled) 
     
     
         45 . A binding protein construct comprising a binding protein sequence of  claim 32  further comprising a linker polypeptide and/or an immunoglobulin constant domain. 
     
     
         46 - 48 . (canceled) 
     
     
         49 . A binding protein conjugate comprising a binding protein construct of  claim 32 , the binding protein conjugate further comprising an immunoadhesion molecule, an imaging agent, a therapeutic agent, or a cytotoxic agent. 
     
     
         50 . An isolated nucleic acid encoding a binding protein amino acid sequence of  claim 32 . 
     
     
         51 . An isolated nucleic acid encoding a sclerostin binding protein construct amino acid sequence of  claim 50 . 
     
     
         52 . A vector comprising the isolated nucleic acid of  claim 51 . 
     
     
         53 . A host cell comprising the vector of  claim 52 . 
     
     
         54 . A method of producing a protein capable of binding sclerostin, comprising culturing the host cell of  claim 53  in culture medium under conditions sufficient to produce a binding protein capable of binding sclerostin. 
     
     
         55 . (canceled) 
     
     
         56 . A pharmaceutical composition comprising the binding protein of  claim 32 , and a pharmaceutically acceptable carrier. 
     
     
         57 . A method for treating a mammal comprising the step of administering to the mammal an effective amount of the composition of  claim 56 . 
     
     
         58 - 61 . (canceled) 
     
     
         62 . A method for treating a subject for a disease or a disorder in which sclerostin activity is detrimental by administering to the subject the binding protein of  claim 32  such that treatment is achieved. 
     
     
         63 . The method of  claim 62 , wherein the disorder is selected from the group consisting of a respiratory disorder; asthma; allergic and nonallergic asthma; asthma due to infection; asthma due to infection with respiratory syncytial virus (RSV); chronic obstructive pulmonary disease (COPD); a condition involving airway inflammation; eosinophilia; fibrosis and/or excess mucus production; cystic fibrosis; pulmonary fibrosis; an atopic disorder; atopic dermatitis; urticaria; eczema; allergic rhinitis; allergic enterogastritis; an inflammatory and/or autoimmune condition of the skin; an inflammatory and/or autoimmune condition of gastrointestinal organs; inflammatory bowel disease (IBD); ulcerative colitis; Crohn's disease; an inflammatory and/or autoimmune condition of the liver; liver cirrhosis; liver fibrosis; liver fibrosis caused by hepatitis B and/or C virus; scleroderma; a tumors; a cancer; hepatocellular carcinoma; glioblastoma; lymphoma; Hodgkin's lymphoma; a viral infection; HTLV-1 infection (e.g., from HTLV-1); a suppression of expression of protective type 1 immune response, and a suppression of expression of protective type 1 immune responses during vaccination. 
     
     
         64 . (canceled) 
     
     
         65 . A method for generating a DVD-binding protein comprising the steps of
 a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α;   b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human sclerostin;   c) constructing polypeptide chains comprising the VD1-(X1)n-VD2-C-(X2)n of any one of  claim 32 ;   e) expressing the polypeptide chains;   such that a DVD-binding protein is generated.