公开(公告)号：US08133471B2

公开(公告)日：2012-03-13

申请号：US12643926

申请日：2009-12-21

Applicant: Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

Inventor： Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

IPC: A61K51/00

CPC classification number: A61K38/08 ,  A61K38/10

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen type-IV with substantially greater affinity than to the native triple helical form of collagen type-IV. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. The invention further describes methods for treating tumors using said antagonists in combination with radiation therapy and therapies comprising the antagonists and radiation treatment.

Abstract translation: 本发明描述了通过施用特异性结合蛋白水解或变性的IV型胶原蛋白的拮抗剂来抑制组织中的血管发生的方法，其具有比IV型胶原天然三螺旋形式更大的亲和力。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。 本发明还描述了使用所述拮抗剂结合放射疗法治疗肿瘤的方法和包括拮抗剂和放射治疗的疗法。

公开(公告)号：US20060216236A1

公开(公告)日：2006-09-28

申请号：US11371620

申请日：2006-03-09

Applicant: Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

Inventor： Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

IPC: A61K51/00 ,  C12Q1/68 ,  G01N33/574 ,  A61K39/395

CPC classification number: G01N33/5011 ,  G01N33/5023

Abstract: The invention provides methods for identifying genes and proteins modulated by an antagonist of αvβ3 that inhibits binding of αvβ3 to an ECM component. It additionally provides methods for using the products of the identified genes, or for using the identified proteins, for inhibiting angiogenesis, tumor metastasis, and other tumor developmental processes, including cell migration, cell adhesion, cell proliferation, and tumor growth and for treating angiogenesis-dependent conditions. The present invention also relates to antagonists of αvβ3, wherein binding of these antagonists to αvβ3 results in modulation of the expression of IGFBP-4 or TSP-1, and methods of using these antagonists for inhibiting angiogenesis, tumor metastasis, and other tumor development processes as well as for treating angiogenesis-dependent conditions.

Abstract translation: 本发明提供用于鉴定由抑制阿尔法博3与ECM组分结合的alphavbeta3拮抗剂调节的基因和蛋白质的方法。 另外提供使用所鉴定的基因的产物或使用鉴定的蛋白质来抑制血管发生，肿瘤转移和其它肿瘤发展过程的方法，包括细胞迁移，细胞粘附，细胞增殖和肿瘤生长以及用于治疗血管生成 依赖条件。 本发明还涉及α-角蛋白3的拮抗剂，其中这些拮抗剂与阿尔茨海因3的结合导致IGFBP-4或TSP-1的表达的调节，以及使用这些拮抗剂抑制血管发生，肿瘤转移和其它肿瘤发展过程的方法 以及用于治疗血管生成依赖性病症。

公开(公告)号：US07662783B2

公开(公告)日：2010-02-16

申请号：US11251442

申请日：2005-10-14

Applicant: Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

Inventor： Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

IPC: A61K38/10

CPC classification number: A61K38/08 ,  A61K38/10

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen type-IV with substantially greater affinity than to the native triple helical form of collagen type-IV. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. The invention further describes methods for treating tumors using said antagonists in combination with radiation therapy and therapies comprising the antagonists and radiation treatment.

Abstract translation: 本发明描述了通过施用特异性结合蛋白水解或变性的IV型胶原蛋白的拮抗剂来抑制组织中的血管发生的方法，其具有比IV型胶原天然三螺旋形式更大的亲和力。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。 本发明还描述了使用所述拮抗剂结合放射疗法治疗肿瘤的方法和包括拮抗剂和放射治疗的疗法。

公开(公告)号：US20090226369A1

公开(公告)日：2009-09-10

申请号：US12118288

申请日：2008-05-12

Applicant: Peter C. Brooks ,  Abebe Akalu

Inventor： Peter C. Brooks ,  Abebe Akalu

IPC: A61K51/08 ,  A61K38/08 ,  A61K38/10 ,  A61K49/14

CPC classification number: C07K7/08

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured laminin with substantially greater affinity than to the native form of laminin. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo.

Abstract translation: 本发明描述了通过施用与蛋白水解或变性层粘连蛋白特异性结合的拮抗剂，以比天然形式的层粘连蛋白具有更大的亲和力来抑制组织中血管生成的方法。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。

公开(公告)号：US20070259817A1

公开(公告)日：2007-11-08

申请号：US11251442

申请日：2005-10-14

Applicant: Peter Brooks ,  Jennifer Roth ,  Abebe Akalu

Inventor： Peter Brooks ,  Jennifer Roth ,  Abebe Akalu

IPC: A61K38/10 ,  A61N5/00 ,  A61N5/10 ,  A61P35/00 ,  C12N13/00

CPC classification number: A61K38/08 ,  A61K38/10

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen type-IV with substantially greater affinity than to the native triple helical form of collagen type-IV. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. The invention further describes methods for treating tumors using said antagonists in combination with radiation therapy and therapies comprising the the antagonists and radiation treatment.

Abstract translation: 本发明描述了通过施用特异性结合蛋白水解或变性的IV型胶原蛋白的拮抗剂来抑制组织中的血管发生的方法，其具有比IV型胶原天然三螺旋形式更大的亲和力。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。 本发明还描述了使用所述拮抗剂结合放射疗法治疗肿瘤的方法和包括拮抗剂和放射治疗的疗法。

公开(公告)号：US20100226852A1

公开(公告)日：2010-09-09

申请号：US12643926

申请日：2009-12-21

Applicant: Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

Inventor： Peter C. Brooks ,  Jennifer Roth ,  Abebe Akalu

IPC: A61K51/00 ,  A61K49/00 ,  G01N33/53

CPC classification number: A61K38/08 ,  A61K38/10

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen type-IV with substantially greater affinity than to the native triple helical form of collagen type-IV. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. The invention further describes methods for treating tumors using said antagonists in combination with radiation therapy and therapies comprising the antagonists and radiation treatment.

Abstract translation: 本发明描述了通过施用特异性结合蛋白水解或变性的IV型胶原蛋白的拮抗剂来抑制组织中的血管发生的方法，其具有比IV型胶原天然三螺旋形式更大的亲和力。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。 本发明还描述了使用所述拮抗剂结合放射疗法治疗肿瘤的方法和包括拮抗剂和放射治疗的疗法。

公开(公告)号：US07387998B2

公开(公告)日：2008-06-17

申请号：US10797626

申请日：2004-03-09

Applicant: Peter C. Brooks ,  Abebe Akalu

Inventor： Peter C. Brooks ,  Abebe Akalu

IPC: A61K38/00 ,  A61K38/04

CPC classification number: C07K7/08

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured laminin with substantially greater affinity than to the native form of laminin. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo.

Abstract translation: 本发明描述了通过施用与蛋白水解或变性层粘连蛋白特异性结合的拮抗剂，以比天然形式的层粘连蛋白具有更大的亲和力来抑制组织中血管生成的方法。 还描述了利用这种拮抗剂治疗肿瘤生长，肿瘤转移或再狭窄的方法，以及在体内和体外在正常或患病组织中使用这些拮抗剂作为血管生成诊断标志物的方法。

公开(公告)号：US20060240002A1

公开(公告)日：2006-10-26

申请号：US11371626

申请日：2006-03-09

Applicant: Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

Inventor： Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

IPC: A61K39/395 ,  C12Q1/68 ,  G01N33/567 ,  C07K16/44

CPC classification number: G01N33/502 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/76

Abstract: The invention provides methods for identifying genes and proteins modulated by an antagonist to a cryptic epitope of an ECM component that specifically binds to the ECM component. It additionally provides methods for using the products of the identified genes, or for using the identified proteins, for inhibiting angiogenesis, tumor metastasis, and other tumor developmental processes, including cell migration, cell adhesion, cell proliferation, and tumor growth and for treating angiogenesis-dependent conditions. The present invention also relates to antagonists of cryptic epitopes of ECM components, wherein binding of these antagonists to cryptic epitopes of ECM components results in modulation of the expression of IGFBP-4, TSP-1, Id-1, p27KIP or p21CIP, and methods of using these antagonists for inhibiting angiogenesis, tumor metastasis, and other tumor development processes as well as for treating angiogenesis-dependent conditions.

Abstract translation: 本发明提供了鉴定由ECM成分的特异性结合ECM成分的拮抗剂拮抗剂调节的基因和蛋白质的方法。 另外提供使用所鉴定的基因的产物或使用鉴定的蛋白质来抑制血管发生，肿瘤转移和其它肿瘤发展过程的方法，包括细胞迁移，细胞粘附，细胞增殖和肿瘤生长以及用于治疗血管生成 依赖条件。 本发明还涉及ECM组分的隐蔽表位的拮抗剂，其中这些拮抗剂与ECM组分的神经表位的结合导致IGFBP-4，TSP-1，Id-1，p27KIP的表达的调节， / SUP>或p21CIP，以及使用这些拮抗剂抑制血管发生，肿瘤转移和其它肿瘤发展过程以及治疗血管生成依赖性病症的方法。

公开(公告)号：US20060216237A1

公开(公告)日：2006-09-28

申请号：US11372367

申请日：2006-03-09

Applicant: Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

Inventor： Peter Brooks ,  Abebe Akalu ,  Alexandra Cretu ,  Desiree Policarpio

IPC: A61K51/00 ,  A61K39/395

CPC classification number: A61K47/642

Abstract: The invention provides compositions comprising IGFBP-4 and methods for inhibiting angiogenesis and tumor development processes, and for treating angiogenesis-dependent conditions, using an insulin growth factor binding protein, IGFBP-4.

Abstract translation: 本发明提供了包含IGFBP-4的组合物和用于抑制血管发生和肿瘤发展过程的方法，以及使用胰岛素生长因子结合蛋白IGFBP-4治疗血管发生依赖性病症的组合物。