公开(公告)号：US09493541B2

公开(公告)日：2016-11-15

申请号：US13088059

申请日：2011-04-15

申请人： Joshua Rabbani ,  James J. Donegan

发明人： Joshua Rabbani ,  James J. Donegan

IPC分类号： A61K38/17 ,  C07K16/18 ,  C07K14/71 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/76

摘要： Provided is a protein comprising an antibody binding site that binds to a sulfated epitope of a Wnt pathway protein that is not Wnt5A, Wnt11, or Wnt3a. Also provided is a composition comprising an isolated and purified Wnt pathway protein, where the protein is sulfated but not glycosylated. Additionally provided is a preparation of a Wnt pathway protein comprising at least one sulfation site and at least one glycosylation site, where all of the Wnt pathway protein in the preparation is glycosylated but not sulfated. Further provided is a composition comprising a peptide less than 75 amino acids or amino acid analogs, the peptide consisting of a fragment of a Wnt pathway protein, wherein the fragment is sulfated. A modified Wnt pathway protein comprising a sulfation site that is not present in the native Wnt pathway protein is also provided. Also provided is a method of detecting or quantifying a sulfated Wnt pathway protein in a preparation. Additionally, a modified Wnt pathway protein lacking a sulfation site that is present in the native Wnt pathway protein is provided. Also provided is methods of treating a subject having a disease exacerbated by Wnt activation. Additionally, a method of treating a subject having a disease exacerbated by Wnt inhibition is provided.

摘要翻译： 提供了包含结合非Wnt5A，Wnt11或Wnt3a的Wnt途径蛋白的硫酸化表位的抗体结合位点的蛋白质。 还提供了包含分离和纯化的Wnt途径蛋白质的组合物，其中蛋白质被硫酸化但未被糖基化。 另外提供了包含至少一个硫酸化位点和至少一个糖基化位点的Wnt途径蛋白质的制剂，其中所述制剂中的所有Wnt途径蛋白质被糖基化但不被硫酸化。 还提供了包含少于75个氨基酸或氨基酸类似物的肽的组合物，所述肽由Wnt途径蛋白质的片段组成，其中所述片段被硫酸化。 还提供了包含不存在于天然Wnt途径蛋白中的硫酸化位点的修饰的Wnt途径蛋白。 还提供了在制剂中检测或定量硫酸化Wnt途径蛋白的方法。 另外，提供了存在于天然Wnt途径蛋白中的缺乏硫酸化位点的修饰的Wnt途径蛋白。 还提供了治疗患有由Wnt活化加重的疾病的受试者的方法。 另外，提供了治疗患有由Wnt抑制加剧的疾病的受试者的方法。

公开(公告)号：US20120071399A1

公开(公告)日：2012-03-22

申请号：US13170634

申请日：2011-06-28

申请人： JOSHUA RABBANI ,  JAMES J. DONEGAN ,  XIAOFENG LI

发明人： JOSHUA RABBANI ,  JAMES J. DONEGAN ,  XIAOFENG LI

IPC分类号： A61K38/10 ,  C07K7/08 ,  C07K19/00 ,  C12N5/00 ,  A61K38/08 ,  A61P19/10 ,  A61P19/08 ,  A61P35/00 ,  A61P3/10 ,  A61P17/14 ,  A61P13/12 ,  A61P19/06 ,  A61P9/12 ,  A61P19/02 ,  A61P9/10 ,  A61P9/00 ,  A61P3/04 ,  C07K7/06

CPC分类号： A61K38/1709 ,  A61K38/08 ,  A61K38/10 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71

摘要： Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner. Additionally provided is a method of enhancing a Wnt signaling pathway comprising contacting an LRP5/6 receptor in the Wnt signaling pathway with either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, in a manner sufficient to enhance the Wnt signaling pathway. Further provided is a method of treating a subject having a disease exacerbated by inhibition of a Wnt signaling pathway comprising administering either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, to the subject in a manner sufficient to reduce the inhibition of the Wnt signaling pathway. Also, a method of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner is provided. The method comprises adding the above-described composition that is capable of inhibiting binding of a protein ligand to its binding partner to the protein ligand and its binding partner in a manner sufficient to inhibit binding of the protein ligand to its binding partner.

公开(公告)号：US20110300159A1

公开(公告)日：2011-12-08

申请号：US12802447

申请日：2010-06-07

申请人： Joshua Rabbani

发明人： Joshua Rabbani

IPC分类号： A61K39/395 ,  C07K7/06 ,  C07K2/00 ,  C40B30/02 ,  A61K38/08 ,  A61P19/10 ,  G01N33/566 ,  C07K16/18 ,  C40B30/04

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K16/44 ,  C07K2317/34

摘要： Provided are antibodies that bind to: a sulfonated epitope of the protein Sclerostin, to Sclerostin portions comprising a sulfonated amino acid and to dimerized forms of Sclerostin. Further provided are compositions and peptides comprising a sulfonated epitope of sclerostin. Also provided by this invention are methods for production of such antibodies, both active and passive, and methods for identifying antibodies specific for sulfonation sites in Sclerostin and other antibodies which discriminate between sulfonated and unsulfonated forms of sclerostin. Physical and virtual screening processes are provided in this invention for identifying compounds whichh disrupt or inhibit sulfonation and the interaction between Sclerostin and binding partners. The antibodies and compositions of the present invention are useful in diagnostic and therapeutic applications directed to Sclerostin-related disorders.

摘要翻译： 提供的是结合：Sclerostin蛋白质的磺化表位，包含磺化氨基酸的硬化蛋白部分和二聚形式的硬化蛋白酶的抗体。 还提供了包含硬化蛋白的磺化表位的组合物和肽。 本发明还提供了用于生产活性和被动型的这种抗体的方法，以及用于鉴定在硬化蛋白中的磺化位点特异的抗体和区分磺化和未磺化形式的硬化蛋白的其它抗体的方法。 在本发明中提供物理和虚拟筛选方法，用于鉴定破坏或抑制磺化的化合物以及硬链蛋白和结合配偶体之间的相互作用。 本发明的抗体和组合物可用于针对硬皮蛋白相关病症的诊断和治疗应用。

公开(公告)号：US20170198033A1

公开(公告)日：2017-07-13

申请号：US15447496

申请日：2017-03-02

申请人： JOSHUA RABBANI

发明人： JOSHUA RABBANI

IPC分类号： C07K16/22

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K16/44 ,  C07K2317/34

摘要： Provided are antibodies that bind to: a sulfonated epitope of the protein Sclerostin, to Sclerostin portions comprising a sulfonated amino acid and to dimerized forms of Sclerostin. Further provided are compositions and peptides comprising a sulfonated epitope of sclerostin. Also provided by this invention are methods for production of such antibodies, both active and passive, and methods for identifying antibodies specific for sulfonation sites in Sclerostin and other antibodies which discriminate between sulfonated and unsulfonated forms of sclerostin. Physical and virtual screening processes are provided in this invention for identifying compounds which disrupt or inhibit sulfonation and the interaction between Sclerostin and binding partners. The antibodies and compositions of the present invention are useful in diagnostic and therapeutic applications directed to Sclerostin-related disorders.

公开(公告)号：US09617323B2

公开(公告)日：2017-04-11

申请号：US12802447

申请日：2010-06-07

申请人： Joshua Rabbani

发明人： Joshua Rabbani

IPC分类号： A61K39/395 ,  C07K7/06 ,  C07K14/51 ,  C07K14/47 ,  C07K14/705 ,  C07K14/71 ,  C07K16/22 ,  C07K16/44

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K16/44 ,  C07K2317/34

摘要： Provided are antibodies that bind to: a sulfonated epitope of the protein Sclerostin, to Sclerostin portions comprising a sulfonated amino acid and to dimerized forms of Sclerostin. Further provided are compositions and peptides comprising a sulfonated epitope of sclerostin. Also provided by this invention are methods for production of such antibodies, both active and passive, and methods for identifying antibodies specific for sulfonation sites in Sclerostin and other antibodies which discriminate between sulfonated and unsulfonated forms of sclerostin. Physical and virtual screening processes are provided in this invention for identifying compounds which disrupt or inhibit sulfonation and the interaction between Sclerostin and binding partners. The antibodies and compositions of the present invention are useful in diagnostic and therapeutic applications directed to Sclerostin-related disorders.

公开(公告)号：US20120052481A1

公开(公告)日：2012-03-01

申请号：US12806950

申请日：2010-08-24

申请人： Elazar Rabbani ,  Joshua Rabbani ,  Praveen Pande ,  Jannis G. Stavrianopoulos

发明人： Elazar Rabbani ,  Joshua Rabbani ,  Praveen Pande ,  Jannis G. Stavrianopoulos

IPC分类号： C12Q1/25 ,  C07K2/00 ,  C12P21/00 ,  C12P13/00 ,  C07K1/14 ,  G01N24/00 ,  C07F9/09

CPC分类号： G01N33/6803 ,  C12Q1/485 ,  C12Y207/01091 ,  C12Y207/11001 ,  G01N33/92 ,  G01N2405/08 ,  G01N2410/00 ,  G01N2440/14 ,  G01N2440/30

摘要： Provided are methods and compositions which are useful for separating, isolating, detecting, and quantifying compounds of interest which have been modified chemically, enzymatically or catalytically from other compounds which have not been so modified. The modifications may take the form of functional groups which are gained, lost or retained by the compounds of interest.

摘要翻译： 提供的方法和组合物可用于分离，分离，检测和定量已经由尚未被这样修饰的其它化合物化学，酶促或催化改性的化合物。 这些修饰可以采取由感兴趣的化合物获得，丢失或保留的官能团的形式。

公开(公告)号：US20110300160A1

公开(公告)日：2011-12-08

申请号：US13088059

申请日：2011-04-15

申请人： Joshua Rabbani ,  James J. Donegan

发明人： Joshua Rabbani ,  James J. Donegan

IPC分类号： A61K39/395 ,  C07K14/47 ,  G01N33/566 ,  A61K38/02 ,  A61K38/17 ,  A61P35/00 ,  A61P19/10 ,  A61P19/08 ,  A61P43/00 ,  A61P19/02 ,  A61P9/10 ,  A61P17/14 ,  A61P13/12 ,  A61P1/16 ,  A61P19/06 ,  A61P9/12 ,  A61P7/06 ,  A61P9/00 ,  A61P29/00 ,  A61P3/04 ,  A61P27/02 ,  C07K16/18

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/76

摘要： Provided is a protein comprising an antibody binding site that binds to a sulfated epitope of a Wnt pathway protein that is not Wnt5A, Wnt11, or Wnt3a. Also provided is a composition comprising an isolated and purified Wnt pathway protein, where the protein is sulfated but not glycosylated. Additionally provided is a preparation of a Wnt pathway protein comprising at least one sulfation site and at least one glycosylation site, where all of the Wnt pathway protein in the preparation is glycosylated but not sulfated. Further provided is a composition comprising a peptide less than 75 amino acids or amino acid analogs, the peptide consisting of a fragment of a Wnt pathway protein, wherein the fragment is sulfated. A modified Wnt pathway protein comprising a sulfation site that is not present in the native Wnt pathway protein is also provided. Also provided is a method of detecting or quantifying a sulfated Wnt pathway protein in a preparation. Additionally, a modified Wnt pathway protein lacking a sulfation site that is present in the native Wnt pathway protein is provided. Also provided is methods of treating a subject having a disease exacerbated by Wnt activation. Additionally, a method of treating a subject having a disease exacerbated by Wnt inhibition is provided.

摘要翻译： 提供了包含结合非Wnt5A，Wnt11或Wnt3a的Wnt途径蛋白的硫酸化表位的抗体结合位点的蛋白质。 还提供了包含分离和纯化的Wnt途径蛋白质的组合物，其中蛋白质被硫酸化但未被糖基化。 另外提供了包含至少一个硫酸化位点和至少一个糖基化位点的Wnt途径蛋白质的制剂，其中所述制剂中的所有Wnt途径蛋白质被糖基化但不被硫酸化。 还提供了包含少于75个氨基酸或氨基酸类似物的肽的组合物，所述肽由Wnt途径蛋白质的片段组成，其中所述片段被硫酸化。 还提供了包含不存在于天然Wnt途径蛋白中的硫酸化位点的修饰的Wnt途径蛋白。 还提供了在制剂中检测或定量硫酸化Wnt途径蛋白的方法。 另外，提供了存在于天然Wnt途径蛋白中的缺乏硫酸化位点的修饰的Wnt途径蛋白。 还提供了治疗患有由Wnt活化加重的疾病的受试者的方法。 另外，提供了治疗患有由Wnt抑制加剧的疾病的受试者的方法。

公开(公告)号：US20170066820A1

公开(公告)日：2017-03-09

申请号：US15273000

申请日：2016-09-22

申请人： JOSHUA RABBANI ,  James J. Donegan

发明人： JOSHUA RABBANI ,  James J. Donegan

IPC分类号： C07K16/22

CPC分类号： C07K16/22 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/76

摘要： Provided is a protein comprising an antibody binding site that binds to a sulfated epitope of a Wnt pathway protein that is not Wnt5A, Wnt1l, or Wnt3a. Also provided is a composition comprising an isolated and purified Wnt pathway protein, where the protein is sulfated but not glycosylated. Additionally provided is a preparation of a Wnt pathway protein comprising at least one sulfation site and at least one glycosylation site, where all of the Wnt pathway protein in the preparation is glycosylated but not sulfated. Further provided is a composition comprising a peptide less than 75 amino acids or amino acid analogs, the peptide consisting of a fragment of a Wnt pathway protein, wherein the fragment is sulfated. A modified Wnt pathway protein comprising a sulfation site that is not present in the native Wnt pathway protein is also provided. Also provided is a method of detecting or quantifying a sulfated Wnt pathway protein in a preparation. Additionally, a modified Wnt pathway protein lacking a sulfation site that is present in the native Wnt pathway protein is provided. Also provided is methods of treating a subject having a disease exacerbated by Wnt activation. Additionally, a method of treating a subject having a disease exacerbated by Wnt inhibition is provided.

摘要翻译： 提供了包含结合不是Wnt5A，Wnt11或Wnt3a的Wnt途径蛋白的硫酸化表位的抗体结合位点的蛋白质。 还提供了包含分离和纯化的Wnt途径蛋白质的组合物，其中蛋白质被硫酸化但未被糖基化。 另外提供了包含至少一个硫酸化位点和至少一个糖基化位点的Wnt途径蛋白质的制剂，其中所述制剂中的所有Wnt途径蛋白质被糖基化但不被硫酸化。 还提供了包含少于75个氨基酸或氨基酸类似物的肽的组合物，所述肽由Wnt途径蛋白质的片段组成，其中所述片段被硫酸化。 还提供了包含不存在于天然Wnt途径蛋白中的硫酸化位点的修饰的Wnt途径蛋白。 还提供了在制剂中检测或定量硫酸化Wnt途径蛋白的方法。 另外，提供了存在于天然Wnt途径蛋白中的缺乏硫酸化位点的修饰的Wnt途径蛋白。 还提供了治疗患有由Wnt活化加重的疾病的受试者的方法。 另外，提供了治疗患有由Wnt抑制加剧的疾病的受试者的方法。

公开(公告)号：US20160317616A1

公开(公告)日：2016-11-03

申请号：US15195017

申请日：2016-06-28

申请人： JOSHUA RABBANI ,  XIAOFENG LI ,  JAMES J. DONEGAN

发明人： JOSHUA RABBANI ,  XIAOFENG LI ,  JAMES J. DONEGAN

IPC分类号： A61K38/17 ,  A61K38/08 ,  C07K14/47 ,  A61K38/10

CPC分类号： A61K38/1709 ,  A61K38/08 ,  A61K38/10 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71

摘要： Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner.

摘要翻译： 提供了包含包含氨基酸和/或氨基酸类似物的肽的组合物，其包含包含Tyr43或Tyr213的硬化蛋白片段的连续序列。 还提供了包含包含少于约75个氨基酸和/或氨基酸类似物的肽的组合物，其包含能够被硫酸化的氨基酸或氨基酸类似物，其中该组合物能够抑制与LRP结合的硬皮蛋白。 还提供了一种组合物，其包含包含小于约75个氨基酸和/或氨基酸类似物的肽，其包含能够翻译后硫酸化的氨基酸或氨基酸类似物，其中组合物能够抑制蛋白质配体的结合， 硫酸化位点到其结合配偶体。

公开(公告)号：US09403882B2

公开(公告)日：2016-08-02

申请号：US13170634

申请日：2011-06-28

申请人： Joshua Rabbani ,  James J. Donegan ,  Xiaofeng Li

发明人： Joshua Rabbani ,  James J. Donegan ,  Xiaofeng Li

IPC分类号： A61K38/10 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71

CPC分类号： A61K38/1709 ,  A61K38/08 ,  A61K38/10 ,  C07K14/47 ,  C07K14/51 ,  C07K14/705 ,  C07K14/71

摘要： Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner. Additionally provided is a method of enhancing a Wnt signaling pathway comprising contacting an LRP5/6 receptor in the Wnt signaling pathway with either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, in a manner sufficient to enhance the Wnt signaling pathway. Further provided is a method of treating a subject having a disease exacerbated by inhibition of a Wnt signaling pathway comprising administering either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, to the subject in a manner sufficient to reduce the inhibition of the Wnt signaling pathway. Also, a method of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner is provided. The method comprises adding the above-described composition that is capable of inhibiting binding of a protein ligand to its binding partner to the protein ligand and its binding partner in a manner sufficient to inhibit binding of the protein ligand to its binding partner.