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1. 发明授权

US07943728B2 Disintegrin variants and their use in treating osteoporosis-induced bone loss and angiogenesis-related diseases 有权
标题翻译： Disintegrin变体及其在治疗骨质疏松症引起的骨丢失和血管发生相关疾病中的应用
公开(公告)号：US07943728B2
公开(公告)日：2011-05-17
申请号：US12004045
申请日：2007-12-20
申请人： Woei-Jer Chuang , Wen-Mei Fu , Tur-Fu Huang , Wenya Huang , Chih-Hsin Tang , Chiu-Yueh Chen
发明人： Woei-Jer Chuang , Wen-Mei Fu , Tur-Fu Huang , Wenya Huang , Chih-Hsin Tang , Chiu-Yueh Chen
IPC分类号： A61K38/00 , A61K38/04 , C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00 , C07K14/00 , C07K16/00 , C07K17/00 , C12P21/06 , C12P15/00 , C12N15/74 , A01N37/18
CPC分类号： C07K14/46 , A61K38/00 , C07K14/745
摘要： Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and/or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and/or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.
摘要翻译：公开了解聚体变体及其药物用途。去整合素变体包含与野生型去整合素相比具有整联蛋白αv＆bgr 3受体 - 拮抗剂活性和显着降低的整合素α1b和bgr3和/或α5＆bgr1受体阻断活性的分离多肽。该变体由编码修饰的氨基酸序列的修饰的整合素核苷酸序列编码，导致与野生型去整合素相比，具有显着降低的对整联蛋白αbb和bgr3和/或α5和bgr的亲和力的多肽。该变体可用于治疗和/或预防哺乳动物中的αv＆bgr 3整联蛋白相关疾病，其包括骨质疏松症，骨肿瘤或癌症生长，血管生成相关的肿瘤生长和转移，骨中的肿瘤转移，恶性肿瘤性高钙血症，血管生成相关眼病，佩吉特氏病，风湿性关节炎和骨关节炎。血管生成相关的眼睛疾病包括年龄相关性黄斑变性，糖尿病性视网膜病变，角膜新生血管性疾病，缺血诱导的新生血管性视网膜病变，高度近视和早产儿视网膜病变。

2. 发明申请

US20110166072A1 Polypeptides Selective for avB3 Integrin, Including Pegylated Polypeptides, And Pharmaceutical Uses Thereof 有权
标题翻译：选择用于avB3整合素的多肽，包括聚乙二醇化多肽及其药物用途
公开(公告)号：US20110166072A1
公开(公告)日：2011-07-07
申请号：US13035579
申请日：2011-02-25
申请人： Woei-Jer Chuang , Wen-Mei Fu , Mannching Sherry Ku , Yen-Lun Huang
发明人： Woei-Jer Chuang , Wen-Mei Fu , Mannching Sherry Ku , Yen-Lun Huang
IPC分类号： A61K38/38 , A61K38/08 , C07K7/06 , A61P35/00 , A61P19/10 , A61P29/00 , A61K38/16 , C07K19/00 , C07K14/00 , C12P21/02 , A61P37/02 , A61P35/04 , A61P19/02
CPC分类号： C07K14/46 , A61K38/00 , C07K14/745
摘要： The invention provides disintegrin variants, and more specifically to disintegrin variants which are selective αvβ3 integrin antagonists for treatment and prevention of αvβ3 integrin-associated diseases. The present invention also relates to pegylated proteins, including proteins comprising a disintegrin variant having an RGD motif variant 48ARLDDL53. The invention also relates to the use of the polypeptides of the invention for the treatment and prevention of αvβ3 integrin-associated diseases.
摘要翻译：本发明提供了解整合素变体，更具体地涉及用于治疗和预防αv＆bgr 3整联蛋白相关疾病的选择性αv＆bgr 3整联蛋白拮抗剂的去整合素变体。本发明还涉及聚乙二醇化的蛋白质，包括包含具有RGD基序变体48ARLDDL53的去整合素变体的蛋白质。本发明还涉及本发明的多肽用于治疗和预防αv＆bgr 3整联蛋白相关疾病的用途。

3. 发明授权

US08183201B2 Methods of treating αvβ3 integrin-associated diseases by administering polypeptides selective for αvβ3 integrin 有权
标题翻译：通过施用αv＆bgr 3整合素选择性多肽治疗αv＆bgr 3整联蛋白相关疾病的方法
公开(公告)号：US08183201B2
公开(公告)日：2012-05-22
申请号：US13035579
申请日：2011-02-25
申请人： Woei-Jer Chuang , Wen-Mei Fu , Mannching Sherry Ku , Yen-Lun Huang
发明人： Woei-Jer Chuang , Wen-Mei Fu , Mannching Sherry Ku , Yen-Lun Huang
IPC分类号： A61K38/00 , A61K38/16 , A61K38/08 , A61P19/02 , A61P29/00 , A61P19/08
CPC分类号： C07K14/46 , A61K38/00 , C07K14/745
摘要： The invention provides disintegrin variants, and more specifically to disintegrin variants which are selective αvβ3 integrin antagonists for treatment and prevention of αvβ3 integrin-associated diseases. The present invention also relates to pegylated proteins, including proteins comprising a disintegrin variant having an RGD motif variant 48ARLDDL53. The invention also relates to the use of the polypeptides of the invention for the treatment and prevention of αvβ3 integrin-associated diseases.
摘要翻译：本发明提供了解整合素变体，更具体地涉及用于治疗和预防αv＆bgr 3整联蛋白相关疾病的选择性αv＆bgr 3整联蛋白拮抗剂的去整合素变体。本发明还涉及聚乙二醇化的蛋白质，包括包含具有RGD基序变体48ARLDDL53的去整合素变体的蛋白质。本发明还涉及本发明的多肽用于治疗和预防αv＆bgr 3整联蛋白相关疾病的用途。

4. 发明授权

US09044436B2 Compositions and methods for the treatment of angiogenesis-related eye diseases 有权
标题翻译：用于治疗血管生成相关眼病的组合物和方法
公开(公告)号：US09044436B2
公开(公告)日：2015-06-02
申请号：US12975630
申请日：2010-12-22
申请人： Woei-Jer Chuang , Wen-Mei Fu , Yen-Lun Huang
发明人： Woei-Jer Chuang , Wen-Mei Fu , Yen-Lun Huang
IPC分类号： A61K38/00 , C07K14/78 , A61K38/17 , A61K47/48
CPC分类号： A61K38/1703 , A61K47/643
摘要： The invention generally relates to compositions and methods of treatment and/or prevention of angiogenesis-related eye diseases using low doses of rhodostomin variants, and in particular, low doses of a fusion protein comprising a rhodostomin variant, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA) where the cysteine residue at position 34 of the HSA amino acid sequence has been replaced with serine.
摘要翻译：本发明一般涉及使用低剂量罗丹明变种治疗和/或预防血管生成相关眼病的组合物和方法，特别是低剂量的包含罗丹明变体的融合蛋白，其中所述罗丹明变体与人血清白蛋白（HSA）的变体，其中HSA氨基酸序列的第34位的半胱氨酸残基被丝氨酸替代。

5. 发明申请

US20110152192A1 Compositions and Methods for the Treatment of Angiogenesis-Related Eye Diseases 有权
标题翻译：用于治疗血管发生相关性眼病的组合物和方法
公开(公告)号：US20110152192A1
公开(公告)日：2011-06-23
申请号：US12975630
申请日：2010-12-22
申请人： Woei-Jer Chuang , Wen-Mei Fu , Yen-Lun Huang
发明人： Woei-Jer Chuang , Wen-Mei Fu , Yen-Lun Huang
IPC分类号： A61K38/16 , A61P27/02
CPC分类号： A61K38/1703 , A61K47/643
摘要： The invention generally relates to compositions and methods of treatment and/or prevention of angiogenesis-related eye diseases using low doses of rhodostomin variants, and in particular, low doses of a fusion protein comprising a rhodostomin variant, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA) where the cysteine residue at position 34 of the HSA amino acid sequence has been replaced with serine.
摘要翻译：本发明一般涉及使用低剂量罗丹明变种治疗和/或预防血管生成相关眼病的组合物和方法，特别是低剂量的包含罗丹明变体的融合蛋白，其中所述罗丹明变体与人血清白蛋白（HSA）的变体，其中HSA氨基酸序列的第34位的半胱氨酸残基被丝氨酸替代。

6. 发明申请

US20110015130A1 Polypeptides Selective for alphavbeta3 Integrin Conjugated With a Variant Of Human Serum Albumin (HSA) And Pharmaceutical Uses Thereof 审中-公开
标题翻译：多肽选择性与alvaveta3整合素与人类血清白蛋白（HSA）及其药物用途的变体共轭
公开(公告)号：US20110015130A1
公开(公告)日：2011-01-20
申请号：US12838926
申请日：2010-07-19
申请人： Woei-Jer Chuang , Wen-Mei Fu
发明人： Woei-Jer Chuang , Wen-Mei Fu
IPC分类号： A61K38/38 , C07K14/765 , C12P21/02 , A61P27/02 , A61P19/10 , A61P3/14 , A61P35/00 , A61P35/04 , A61P29/00
CPC分类号： C07K14/70546 , A61K38/00
摘要： The invention generally relates to fusion proteins comprising a rhodostomin variant having an RGD motif variant 48ARLDDL53, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA). The invention also relates to the use of these fusion proteins for treatment and prevention of αvβ3 integrin-associated diseases.
摘要翻译：本发明一般涉及包含具有RGD基序变体48ARLDDL53的罗丹明变体的融合蛋白，其中所述罗丹明变体与人血清白蛋白（HSA）的变体缀合。本发明还涉及这些融合蛋白用于治疗和预防αv＆bgr 3整联蛋白相关疾病的用途。

7. 发明申请

US20080188413A1 Disintegrin variants and pharmaceutical uses thereof 有权
标题翻译：消融素变体及其药物用途
公开(公告)号：US20080188413A1
公开(公告)日：2008-08-07
申请号：US12004045
申请日：2007-12-20
申请人： Woei-Jer Chuang , Wen-Mei Fu , Tur-Fu Huang , Wenya Huang , Chih-Hsin Tang , Chiu-Yueh Chen
发明人： Woei-Jer Chuang , Wen-Mei Fu , Tur-Fu Huang , Wenya Huang , Chih-Hsin Tang , Chiu-Yueh Chen
IPC分类号： A61K38/16 , A61K38/02 , A61K38/08 , C07K2/00 , C07K14/00 , C07K7/06 , C12P21/00 , C07H21/00 , A61P35/00 , A61P19/10 , A61P19/02
CPC分类号： C07K14/46 , A61K38/00 , C07K14/745
摘要： Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and/or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and/or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.
摘要翻译：公开了解聚体变体及其药物用途。去整合素变体包含与野生型去整合素相比具有整合素α1受体 - 拮抗剂活性的分离的多肽和显着降低的整联蛋白α1bβ3和/或α5β1受体阻断活性。该变体由编码修饰的氨基酸序列的修饰的整合素核苷酸序列编码，导致与野生型去整合素相比，具有显着降低的对整联蛋白αββ和/或α5β1的整合素的多肽的多肽。该变体可用于治疗和/或预防哺乳动物中的α2β1整联蛋白相关疾病，其包括骨质疏松症，骨肿瘤或癌症生长，血管生成相关的肿瘤生长和转移，骨中的肿瘤转移，恶性肿瘤性高钙血症，血管生成 - 相关的眼睛疾病，佩吉特氏病，风湿性关节炎和骨关节炎。血管生成相关的眼睛疾病包括年龄相关性黄斑变性，糖尿病性视网膜病变，角膜新生血管性疾病，缺血诱导的新生血管性视网膜病变，高度近视和早产儿视网膜病变。

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