US2012201815A1PendingUtilityA1

Methods of altering bone growth by administration of sost or wise antagonist or agonist

59
Individually held — no corporate assignee on recordPriority: Dec 29, 2006Filed: Mar 15, 2012Published: Aug 9, 2012
Est. expiryDec 29, 2026(~0.4 yrs left)· nominal 20-yr term from priority
Inventors:Debra Ellies
A61P 43/00A61K 38/1709A61K 39/3955A61L 2300/256A61L 2300/432C07K 2317/76C07K 2317/55A61P 13/12A61L 2430/02A61K 31/713A61K 31/59A61K 31/7088A61P 1/02A61L 27/12C07K 2317/24A61L 27/54A61K 38/1875A61K 39/395C07K 16/22A61P 19/00A61P 19/08A61K 45/06A61K 31/66
59
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Claims

Abstract

The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.

Claims

exact text as granted — not AI-modified
1 - 40 . (canceled) 
     
     
         41 . A method of promoting local bone growth, comprising the steps of administering a therapeutic amount of a Sost, Wise, or LRP antagonist locally to a mammalian patient in need thereof. 
     
     
         42 . The method according to  claim 41 , further comprising the step of administering to said mammalian patient a biocompatible matrix and/or porous structural scaffold conducive to anchoring new bone growth. 
     
     
         43 . The method according to  claim 42 , comprising administering said biocompatible matrix, wherein said matrix comprises one or more of the material selected from the group consisting of a calcium salt, calcium sulfate, calcium carbonate, autograft, hydroxyapatite, demineralized bone, allograft or tricalcium phosphate. 
     
     
         44 . The method according to  claim 42 , comprising administering said porous structural scaffold, wherein said porous structural scaffold comprises at least one material selected from the group consisting of Rad16 Hydrogel, hydrogel, DPHP hydrogel, silica particles, collagen, chitosan, alginate, and synthetic biodegradable polymers. 
     
     
         45 . A method of promoting bone growth, comprising the steps of surgically implanting, in a mammalian patient in need thereof, a therapeutic amount of a Sost, Wise, or LRP antagonist together with a BMP recombinant protein. 
     
     
         46 . The method according to  claim 45 , further comprising the step of surgically implanting in said mammalian patient a biocompatible matrix and/or porous structural scaffold conducive to anchoring new bone growth. 
     
     
         47 . The method according to  claim 46 , comprising implanting said biocompatible matrix, wherein said matrix comprises at least one material selected from the group consisting of a calcium salt, calcium sulfate, calcium carbonate, autograft, hydroxyapatite, demineralized bone, allograft and tricalcium phosphate. 
     
     
         48 . The method according to  claim 46 , comprising implanting said porous structural scaffold, wherein said porous structural scaffold comprises at least one material selected from the group consisting of Rad16 Hydrogel, hydrogel, DPHP hydrogel, silica particles, collagen, chitosan, alginate, and synthetic biodegradable polymers. 
     
     
         49 . The method according to  claim 46 , wherein said Sost, Wise, or LRP antagonist comprises a blocking antibody or FAB fragment designed from sequences having at least 75% identity to at least 10 contiguous amino acids of a sequence selected from the group consisting of SEQ ID NOS: 1-23, wherein the blocking antibody thereby provides new local bone formation. 
     
     
         50 . The method according to  claim 49 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         51 . The method according to  claim 50 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         52 . The method according to  claim 49 , wherein said Sost, Wise or LRP antagonist comprises a blocking antibody or FAB fragment specifically binding to SEQ ID NO:23. 
     
     
         53 . The method according to  claim 52 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         54 . The method according to  claim 53 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         55 . An orthopedic or periodontal medical device, comprising a structural support and/or biocompatible matrix, wherein an implantable portion of said structural support and/or biocompatible matrix is adapted to be permanently implanted within a mammalian body, said implanted structure support and/or biocompatible matrix being retained in said body by new bone growth, said structural support bearing at least a partial external coating of a Sost antagonist. 
     
     
         56 . The medical device according to  claim 55 , wherein said external coating completely coats said implantable portion of said structural support. 
     
     
         57 . The medical device according to  claim 55 , wherein said implantable portion of said structural support comprises said biocompatible matrix or porous structural scaffold. 
     
     
         58 . The medical device according to  claim 42 , comprising said biocompatible matrix, wherein said matrix comprises at least one material selected from the group consisting of a calcium salt, calcium sulfate, calcium carbonate, autograft, hydroxyapatite, demineralized bone, allograft and tricalcium phosphate. 
     
     
         59 . The method according to  claim 42 , comprising said porous structural scaffold, wherein said porous structural scaffold comprises at least one material selected from the group consisting of Rad16 Hydrogel, hydrogel, DPHP hydrogel, silica particles, collagen, chitosan, alginate, and synthetic biodegradable polymers. 
     
     
         60 . The medical device according to  claim 57 , wherein said Sost antagonist comprises an antibody or FAB fragment specifically binding a peptide having at least 75% identity to at least 5 contiguous amino acids from any one of SEQ ID NOS: 1-23. 
     
     
         61 . The medical device according to  claim 60 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         62 . The medical device according to  claim 61 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         63 . The medical device according to  claim 60 , wherein said Sost antagonist comprises an antibody or FAB fragment specifically binding a peptide having at least 75% identity to at least 5 contiguous amino acids of SEQ ID NO:23. 
     
     
         64 . The medical device according to  claim 63 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         65 . The medical device according to  claim 64 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         66 . A method of increasing bone density, comprising the steps of administering to a mammalian patient in need thereof, a therapeutic comprising an effective amount of (i) a Sost, Wise, or LRP antagonist together with (ii) an antiresorptive drug at same time or in succession. 
     
     
         67 . The method according to  claim 66 , wherein bone density is increased systemically. 
     
     
         68 . The method according to  claim 42 , wherein the therapeutic is surgically implanted. 
     
     
         69 . The method according to  claim 66 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin or analog, Vitamin D or analog, or a Rank antagonist. 
     
     
         70 . The method according to  claim 66 , wherein said therapeutic comprises a Sost antagonist comprising an antibody or FAB fragment specifically binding a peptide having at least 75% identity to at least 7 contiguous amino acids from SEQ ID NOS: 1-23. 
     
     
         71 . The method according to  claim 70 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         72 . The method according to  claim 71 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         73 . The method according to  claim 72 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin or analog, Vitamin D or analog, or a Rank antagonist 
     
     
         74 . The method according to  claim 66 , wherein said therapeutic comprises a Sost antagonist comprising an antibody or FAB fragment specifically binding a peptide having at least 75% identity to at least 5 contiguous amino acids from SEQ ID NO:23. 
     
     
         75 . The method according to  claim 74 , wherein said antibody or FAB fragment is a monoclonal antibody. 
     
     
         76 . The method according to  claim 75 , wherein said antibody is a humanized antibody or FAB fragment. 
     
     
         77 . The method according to  claim 76 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin or analog, Vitamin D or analog, or a Rank antagonist. 
     
     
         78 . A method of reducing bone, comprising the steps of systemically administering or surgically implanting a therapeutic amount of a Sost or Wise agonist to a mammalian patient in need thereof. 
     
     
         79 . The method according to  claim 78 , wherein said Sost or Wise agonist is a peptide having at least 75% identity to at least 5 contiguous amino acids with SEQ ID NO:23. 
     
     
         80 . The method according to  claim 78 , wherein said Sost or Wise agonist comprises a sequence having at least 75% identity to at least 5 contiguous amino acids to SEQ ID NO: 1. 
     
     
         81 . The method according to  claim 78 , wherein said bone formation is reduced locally. 
     
     
         82 . The method according to  claim 79 , wherein said bone formation is reduced locally. 
     
     
         83 . The method according to  claim 80 , wherein said bone formation is reduced locally. 
     
     
         84 . The method according to  claim 78 , wherein said bone formation is reduced systemically. 
     
     
         85 . The method according to  claim 79 , wherein said bone formation is reduced systemically. 
     
     
         86 . The method according to  claim 80 , wherein said bone formation is reduced systemically. 
     
     
         87 . A method of protecting a mammalian kidney from glomuleronephritis comprising administering, to a patient exposed to chemical injury, a therapeutic amount of a Sost or Wise antagonist.

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