Antibodies Specific for Sclerostin and Methods for Increasing Bone Mineralization

Abstract

Compositions and methods relating to antibodies that specifically bind to TGF-beta binding proteins are provided. These methods and compositions relate to altering bone mineral density by interfering with the interaction between a TGF-beta binding protein sclerostin and a TGF-beta superfamily member, particularly a bone morphogenic protein. Increasing bone mineral density has uses in diseases and conditions in which low bone mineral density typifies the condition, such as osteopenia, osteoporosis, and bone fractures.

1 .- 51 . (canceled) 
     
     
         52 . An isolated polynucleotide encoding an antibody, or antigen binding fragment thereof, that specifically binds to an epitope of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         53 . The polynucleotide of  claim 52 , wherein the antibody, or antigen-binding fragment thereof, specifically binds to an epitope of amino acids 86-105 of SEQ ID NO: 1. 
     
     
         54 . The polynucleotide of  claim 52 , wherein the antibody, or antigen-binding fragment thereof, specifically binds to an epitope of amino acids 96-111 of SEQ ID NO: 1. 
     
     
         55 . The polynucleotide of  claim 52 , wherein the antibody is a human antibody, a humanized antibody or a chimeric antibody. 
     
     
         56 . The polynucleotide of  claim 52 , wherein the antibody is an antigen-binding fragment. 
     
     
         57 . The polynucleotide of  claim 52 , wherein the antibody comprises an antigen-binding fragment selected from the group consisting of F(ab′)2, Fab, Fab′, Fd, and Fv. 
     
     
         58 . The polynucleotide of  claim 52 , wherein the antibody comprises an Fv fragment. 
     
     
         59 . The polynucleotide of  claim 52 , wherein the antibody comprises a single chain antibody. 
     
     
         60 . The polynucleotide of  claim 52 , wherein the antibody comprises at least one heavy chain and at least one light chain. 
     
     
         61 . An isolated polynucleotide encoding an antibody, or antigen binding fragment thereof, that binds to a peptide consisting of amino acids 86-111 of SEQ ID NO: 1 with an affinity (Kd) of less than or equal to about 10 −7  M. 
     
     
         62 . The polynucleotide of  claim 61 , wherein the antibody is a human antibody, a humanized antibody or a chimeric antibody. 
     
     
         63 . The polynucleotide of  claim 61 , wherein the antibody, or an antigen-binding fragment thereof, binds to a peptide consisting of amino acids 86-105 of SEQ ID NO: 1. 
     
     
         64 . The polynucleotide of  claim 63 , wherein the antibody is a human antibody, a humanized antibody or a chimeric antibody. 
     
     
         65 . The polynucleotide of  claim 61 , wherein the antibody is an antigen-binding fragment. 
     
     
         66 . The polynucleotide of  claim 61 , wherein the antibody comprises at least one heavy chain and at least one light chain. 
     
     
         67 . An isolated polynucleotide encoding a heavy chain of an antibody, or antigen binding fragment thereof, that specifically binds to an epitope of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         68 . An isolated polynucleotide encoding a light chain of an antibody, or antigen binding fragment thereof, that specifically binds to an epitope of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         69 . An isolated polynucleotide encoding a heavy chain of an antibody, or antigen binding fragment thereof, that specifically binds to a peptide consisting of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         70 . An isolated polynucleotide encoding a light chain of an antibody, or antigen binding fragment thereof that specifically binds to a peptide consisting of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         71 . A vector comprising the polynucleotide of any one of  claims 52 - 70 , operably linked to a transcriptional or translational regulatory element. 
     
     
         72 . A host cell comprising the polynucleotide of any of  claims 52 - 70 . 
     
     
         73 . A host cell comprising the polynucleotide of  claim 67  and the polynucleotide of  claim 68 . 
     
     
         74 . A host cell comprising the polynucleotide of  claim 69  and the polynucleotide of  claim 70 . 
     
     
         75 . A host cell comprising a vector of  claim 71 . 
     
     
         76 . A host cell that is capable of expressing an antibody, or antigen binding fragment thereof, that specifically binds to an epitope of amino acids 86-111 of SEQ ID NO: 1. 
     
     
         77 . The host cell of  claim 76 , wherein the antibody, or antigen binding fragment thereof specifically binds to an epitope of amino acids 86-105 of SEQ ID NO: 1. 
     
     
         78 . A method of producing an antibody comprising the step of culturing the host cell of  claim 72  and isolating the antibody produced therefrom. 
     
     
         79 . A method of producing an antibody comprising the step of culturing the host cell of  claim 73  and isolating the antibody produced therefrom. 
     
     
         80 . A method of producing an antibody comprising the step of culturing the host cell of  claim 74  and isolating the antibody produced therefrom. 
     
     
         81 . A method of producing an antibody comprising the step of culturing the host cell of  claim 75  and isolating the antibody produced therefrom. 
     
     
         82 . A method of producing an antibody comprising the step of culturing the host cell of  claim 76  and isolating the antibody produced therefrom.