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51. 发明授权

US06172205B2 Synthetic process toward total synthesis of eleutherobin and its analogues and uses thereof 失效
标题翻译：合成方法，全面合成eleutherobin及其类似物及其用途
公开(公告)号：US06172205B2
公开(公告)日：2001-01-09
申请号：US09210290
申请日：1998-12-11
申请人： Samuel J. Danishefsky , Xiao-Tao Chen , Clare E. Gutteridge , Samit K. Bhattacharya , Bishan Zhou
发明人： Samuel J. Danishefsky , Xiao-Tao Chen , Clare E. Gutteridge , Samit K. Bhattacharya , Bishan Zhou
IPC分类号： C07G1100
CPC分类号： C07H15/04 , C07H15/26 , C07H17/04
摘要： This invention provides a process for the preparation of a Eleutherobin derivative of the formula: wherein R1 is a hydrogen, ester, nitrile or C2H4—R wherein R4 is a carbohydrate, an alcohol an amine, an amide, an alkyne, or, R2 is a linear or branched alkyl moiety, R3 is an ester, an amide, a carbamate, an acetal compound,an ether or a urethane, R4 is a hydrogen or CH2,position C2 and C3 is cis or trans,position C8 is &agr; or &bgr; and a compound is produced having the structures: Additionally, this experiment provides a method for inhibiting growth of cancerous cells comprising contracting an amount of Eleutherobin derivative effective to inhibit the growth of said cells. Further provided is a method for treating cancer in a subject which comprises administering to the subject a therapeutically effective amount of the Eleutherobin derivative.
摘要翻译：本发明提供了制备下式的十六烯炔酯衍生物的方法：其中R1是氢，酯，腈或C2H4-R，其中R4是碳水化合物，醇和胺，酰胺，炔烃，或者R2是直链或支链烷基部分，R3为酯，酰胺，氨基甲酸酯，缩醛化合物，醚或氨基甲酸酯，R4为氢或CH2，C2和C3为顺式或反式，C8为α或β 并且产生具有以下结构的化合物：另外，该实验提供了抑制癌细胞生长的方法，包括收缩一定量的有效抑制所述细胞生长的埃叶塞类衍生物。还提供了一种用于治疗受试者的癌症的方法，其包括向所述受试者施用治疗有效量的埃柳塞星衍生物。

52. 发明授权

US5708163A Synthesis of the breast tumor-associated antigen defined by monoclonalantibody MBRL and uses thereof 失效
标题翻译：由单克隆抗体MBRL定义的乳腺肿瘤相关抗原的合成及其用途
公开(公告)号：US5708163A
公开(公告)日：1998-01-13
申请号：US430355
申请日：1995-04-28
申请人： Samuel J. Danishefsky , Mark T. Bilodeau , Shuang Hua Hu , Tae Kyo Park , John T. Randolph , In Jong Kim , Philip O. Livingston
发明人： Samuel J. Danishefsky , Mark T. Bilodeau , Shuang Hua Hu , Tae Kyo Park , John T. Randolph , In Jong Kim , Philip O. Livingston
IPC分类号： C07H11/00 , A61K31/70 , A61K31/7028 , A61K31/7042 , A61K31/7048 , A61K38/00 , A61K39/00 , A61K39/39 , A61P35/00 , A61P37/04 , C07H3/06 , C07H15/10 , C07H15/18 , C07H17/02 , C07H17/04 , C07K1/04 , C07K9/00 , C07K16/30 , C07K16/44 , C07H1/00 , C07H5/06 , C07H17/00 , C08B37/00
CPC分类号： C07H15/10 , A61K39/0011 , C07H15/18 , C07H17/02 , C07H3/06 , C07K1/04 , C07K16/3015 , C07K16/44 , C07K9/005 , A61K38/00
摘要： The present invention provides a process for synthesizing a compound having the structure: ##STR1## wherein R is H, as well as related oligosaccharides useful as a vaccine for inducing antibodies to human breast cancer cells in an adjuvant therapy therefor.
摘要翻译：本发明提供了一种合成具有以下结构的化合物的方法：其中R是H，以及可用作用于在其辅助治疗中诱导人乳腺癌细胞的抗体的疫苗的相关寡糖。

53. 发明授权

US5679769A Synthesis of asparagine-linked glycopeptides on a polymeric solid support 失效
标题翻译：在聚合物固体支持物上合成天冬酰胺连接的糖肽
公开(公告)号：US5679769A
公开(公告)日：1997-10-21
申请号：US477776
申请日：1995-06-07
申请人： Samuel J. Danishefsky , Jacques Roberge , Xenia Beebe
发明人： Samuel J. Danishefsky , Jacques Roberge , Xenia Beebe
IPC分类号： A61K38/00 , A61K39/00 , C07H3/06 , C07H15/10 , C07H15/18 , C07H17/02 , C07K1/04 , C07K9/00 , C07K16/30 , C07K16/44 , A61K31/02
CPC分类号： A61K39/0011 , C07H15/10 , C07H15/18 , C07H17/02 , C07H3/06 , C07K1/04 , C07K16/3015 , C07K16/44 , C07K9/005 , A61K38/00
摘要： The present invention provides a process for synthesizing a glycopeptide having the structure: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are each independently H, OH, OR.sup.1, NH.sub.2, NHCOR.sup.i, F, CH.sub.2 OH, CH.sub.2 OR.sup.i, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group, where R.sup.i is H, CHO, CO.sub.2 R.sup.ii, a linear or branched chain alkyl, arylalkyl or aryl group, or an oligosaccharide moiety, etc., wherein R.sub.0 is H, a linear or branched chain alkyl, arylalkyl or aryl group; wherein R.sub.10 is a substituted or unsubstituted linear or branched chain acyl, arylacyl or aroyl group; wherein R.sub.11�x! represents X amino acid side-chains, and denotes position from the N-terminus, and R.sub.13�y! represents Y amino acid side-chains, and denotes position from the C-terminus, wherein a, b, c, h, i, j, r, s and t are each independently an integer between about 0 and about 3; wherein m and n are each independently an integer between about 0 and about 5; and wherein x, x'(N), y and y'(N) are each independently an integer between about 0 and,about 25; such glycopeptides being useful as a vaccine for inducing antibodies to human breast cancer cells in an adjuvant therapy therefor.
摘要翻译：本发明提供一种合成具有以下结构的糖肽的方法：其中R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8各自独立地为H，OH，OR 1，NH 2，NHCOR 1 ，F，CH2OH，CH2ORi或取代或未取代的直链或支链烷基，芳烷基或芳基，其中R 1为H，CHO，CO 2 R 11，直链或支链烷基，芳烷基或芳基或寡糖部分等其中R 0是H，直链或支链烷基，芳烷基或芳基; 其中R 10是取代或未取代的直链或支链酰基，芳基酰基或芳酰基; 其中R11 [x]表示X氨基酸侧链，表示从N-末端的位置，R13 [y]表示Y氨基酸侧链，表示C末端的位置，其中a，b，c ，h，i，j，r，s和t各自独立地为约0和约3之间的整数; 其中m和n各自独立地为约0和约5之间的整数; 并且其中x，x'（N），y和y'（N）各自独立地为约0和约25之间的整数; 这样的糖肽可用作用于在其辅助治疗中诱导人乳腺癌细胞的抗体的疫苗。

54. 发明授权

US08754192B2 Compositions comprising homogeneously glycosylated erythropoietin 有权
标题翻译：包含均匀糖基化促红细胞生成素的组合物
公开(公告)号：US08754192B2
公开(公告)日：2014-06-17
申请号：US12296608
申请日：2007-04-11
申请人： Samuel J. Danishefsky , J. David Warren , Jiehao Chen , Bin Wu , Gong Chen , Qian Wan , Zhongping Tan , Cindy Kan , Yu Yuan , Zihao Hua , Krishnakumar Ranganathan , John D. Trzupek
发明人： Samuel J. Danishefsky , J. David Warren , Jiehao Chen , Bin Wu , Gong Chen , Qian Wan , Zhongping Tan , Cindy Kan , Yu Yuan , Zihao Hua , Krishnakumar Ranganathan , John D. Trzupek
IPC分类号： C07K1/00 , C07K14/00 , C07K17/00 , A61K38/00
CPC分类号： C07K14/505 , C07K9/00 , C12P21/005
摘要： The present invention provides isolated homogeneous polyfunctionalized proteins (e.g., erythropoietin), isolated glycopeptides, and a method for preparing polyfunctionalized peptides and/or proteins via cysteine-free native chemical ligation. In certain embodiments, the invention provides an isolated homogeneous polyfunctionalized protein having the structure (I). In certain other embodiments, the invention provides an isolated glycopeptide having Formula (II). In certain other embodiments, the inventive method is a method for preparing a polyfunctionalized peptide comprising a peptidic backbone made up of four or more amino acids, wherein two or more non-adjacent amino acids are independently substituted with a moiety having the structure (III) -LH. wherein A and L1 are as defined herein.
摘要翻译：本发明提供了分离的均相多官能化蛋白质（例如红细胞生成素），分离的糖肽，以及通过不含半胱氨酸的天然化学连接制备多官能化肽和/或蛋白质的方法。在某些实施方案中，本发明提供具有结构（I）的分离的均相多官能化蛋白质。在某些其它实施方案中，本发明提供了具有式（II）的分离的糖肽。在某些其他实施方案中，本发明的方法是制备多功能化肽的方法，其包含由四个或更多个氨基酸组成的肽主链，其中两个或多个不相邻氨基酸独立地被具有结构（III）的部分取代， -LH。其中A和L1如本文所定义。

55. 发明申请

US20140024705A1 MIGRASTATINS AND USES THEREOF 有权
标题翻译：偏移及其用途
公开(公告)号：US20140024705A1
公开(公告)日：2014-01-23
申请号：US14110115
申请日：2012-04-06
申请人： Samuel J. Danishefsky , Joan Massague , Manuel Valiente Cortes , Thordur Oskarsson , Malcom Moore , Nicolas Lecomte , Ouathek Ouerfelli , Guangli Yang
发明人： Samuel J. Danishefsky , Joan Massague , Manuel Valiente Cortes , Thordur Oskarsson , Malcom Moore , Nicolas Lecomte , Ouathek Ouerfelli , Guangli Yang
IPC分类号： C07D313/00
CPC分类号： C07D313/00 , A61K31/335
摘要： The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
摘要翻译：本发明提供化合物，其药学上可接受的组合物及其使用方法。

56. 发明申请

US20120263749A1 POLYVALENT CONJUGATE VACCINE FOR CANCER 有权
标题翻译：多糖联合疫苗用于癌症
公开(公告)号：US20120263749A1
公开(公告)日：2012-10-18
申请号：US13314521
申请日：2011-12-08
申请人： Philip O. Livingston , Govindaswami Ragupathi , Samuel J. Danishefsky
发明人： Philip O. Livingston , Govindaswami Ragupathi , Samuel J. Danishefsky
IPC分类号： A61K39/385 , A61P35/00
CPC分类号： A61K39/0011 , A61K39/385 , A61K47/646 , A61K2039/545 , A61K2039/55577 , A61K2039/575 , A61K2039/6081 , A61K2039/627 , A61K2039/70
摘要： This invention provides a polyvalent vaccine comprising at least two conjugated antigens selected from a group containing glycolipid antigen, polysaccharide antigen, mucin antigen, glycosylated mucin antigen and an appropriate adjuvant. This invention also provides a multivalent vaccine comprising at least two of the following: glycosylated MUC-1-32mer, Globo H, GM2, Ley, Tn(c), sTN(c), and TF(c). This invention provides the vaccine above, wherein the adjuvant is saponin-based adjuvant. This invention provides a method for inducing immune response in a subject comprising administering an effective amount of the vaccine above to the subject. Finally, this invention provides a method for treating cancer in a subject comprising administering an appropriate amount of the vaccine above to the subject.
摘要翻译：本发明提供了包含至少两种选自包含糖脂抗原，多糖抗原，粘蛋白抗原，糖基化粘蛋白抗原和合适佐剂的缀合抗原的多价疫苗。本发明还提供了包含以下至少两种的多价疫苗：糖基化MUC-1-32mer，Globo H，GM2，Ley，Tn（c），sTN（c）和TF（c）。本发明提供上述疫苗，其中佐剂是基于皂苷的佐剂。本发明提供了一种在受试者中诱导免疫应答的方法，包括向受试者施用有效量的上述疫苗。最后，本发明提供了一种用于治疗受试者的癌症的方法，包括向受试者施用适量的上述疫苗。

57. 发明授权

US07854934B2 Glycoconjugates, glycoamino acids, intermediates thereto, and uses thereof 有权
标题翻译：糖缀合物，糖氨基酸，其中间体及其用途
公开(公告)号：US07854934B2
公开(公告)日：2010-12-21
申请号：US10209618
申请日：2002-07-31
申请人： Samuel J. Danishefsky , Don M. Coltart , Stacy J. Keding , Kaustav Biswas , Philip O. Livingston , Govindaswami Ragupathi , Jennifer R. Allen , Lawrence Williams
发明人： Samuel J. Danishefsky , Don M. Coltart , Stacy J. Keding , Kaustav Biswas , Philip O. Livingston , Govindaswami Ragupathi , Jennifer R. Allen , Lawrence Williams
IPC分类号： A01N43/04 , A61K39/385 , A61K31/70 , A61K31/715
CPC分类号： C07H15/04 , A61K31/715 , A61K38/00 , A61K39/0011 , A61K2039/55555 , A61K2039/55577 , A61K2039/55594 , A61K2039/6081 , A61K2039/627 , C07B2200/11 , C07H15/10 , C07H15/18 , C07K1/1077 , C07K5/06139 , C07K9/00 , C07K14/43509
摘要： The present invention provides novel glycosides and glycoconjugates, glycoamino acids, and methods for the synthesis thereof. In another aspect, the present invention provides novel clustered glycopeptides and methods for the synthesis thereof. In still another aspect, the present invention provides methods for the treatment of cancer, preferably for the prevention of recurrence of cancer, and methods for inducing antibodies in a subject, comprising administering to a subject in need, an effective amount of any of the inventive glycopeptides as disclosed herein, either in conjugated form or unconjugated and in combination with a suitable immunogenic carrier.
摘要翻译：本发明提供新的糖苷和糖缀合物，糖基氨基酸及其合成方法。另一方面，本发明提供了新颖的聚合糖肽及其合成方法。另一方面，本发明提供了治疗癌症的方法，优选用于预防癌症复发，以及用于在受试者中诱导抗体的方法，包括向有需要的受试者施用有效量的本发明的任何一种本文公开的糖肽，以缀合形式或未偶联的，并与合适的免疫原性载体组合。

58. 发明授权

US07550146B2 Glycopeptide conjugates and uses thereof 有权
标题翻译：糖肽缀合物及其用途
公开(公告)号：US07550146B2
公开(公告)日：2009-06-23
申请号：US10898410
申请日：2004-07-23
申请人： Samuel J. Danishefsky , Dalibor Sames , Samuel Hintermann , Peter Glunz , Govindaswami Ragupathi , Philip O. Livingston , Kenneth O. Lloyd , Valery Kudryashov
发明人： Samuel J. Danishefsky , Dalibor Sames , Samuel Hintermann , Peter Glunz , Govindaswami Ragupathi , Philip O. Livingston , Kenneth O. Lloyd , Valery Kudryashov
IPC分类号： A61K38/14 , A61K39/385 , C07K9/00
CPC分类号： C07H5/06
摘要： The present invention provides novel glycoconjugates such as glycopeptides, as well as convergent methods for the synthesis thereof. An exemplary preparative approach is exemplified by the synthesis of the mucin motif commonly found on epithelial tumor cell surfaces. The present invention further provides compositions and methods of treating cancer using the glycoconjugates of the invention.
摘要翻译：本发明提供了新的糖缀合物，如糖肽，以及其合成方法。通过合成通常在上皮肿瘤细胞表面上发现的粘蛋白基序来举例说明一个示例性的制备方法。本发明还提供了使用本发明的糖缀合物治疗癌症的组合物和方法。

59. 发明申请

US20090060938A1 Polyvalent Conjugate Vaccine for Cancer 有权
标题翻译：多价共轭疫苗用于癌症
公开(公告)号：US20090060938A1
公开(公告)日：2009-03-05
申请号：US12262729
申请日：2008-10-31
申请人： Philip O. Livingston , Govindaswami Ragupathi , Samuel J. Danishefsky
发明人： Philip O. Livingston , Govindaswami Ragupathi , Samuel J. Danishefsky
IPC分类号： A61K39/385 , A61P35/00 , A61P37/04
CPC分类号： A61K39/0011 , A61K39/385 , A61K47/646 , A61K2039/545 , A61K2039/55577 , A61K2039/575 , A61K2039/6081 , A61K2039/627 , A61K2039/70
摘要： This invention provides a polyvalent vaccine comprising at least two conjugated antigens selected from a group containing glycolipid antigen, polysaccharide antigen, mucin antigen, glycosylated mucin antigen and an appropriate adjuvant. This invention also provides a multivalent vaccine comprising at least two of the following: glycosylated MUC-1-32mer, Globo H, GM2, Ley, Tn(c), sTN(c), and TF(c). This invention provides the vaccine above, wherein the adjuvant is saponin-based adjuvant. This invention provides a method for inducing immune response in a subject comprising administering an effective amount of the vaccine above to the subject. Finally, this invention provides a method for treating cancer in a subject comprising administering an appropriate amount of the vaccine above to the subject.
摘要翻译：本发明提供了包含至少两种选自包含糖脂抗原，多糖抗原，粘蛋白抗原，糖基化粘蛋白抗原和合适佐剂的缀合抗原的多价疫苗。本发明还提供了包含以下至少两种的多价疫苗：糖基化MUC-1-32mer，Globo H，GM2，Ley，Tn（c），sTN（c）和TF（c）。本发明提供上述疫苗，其中佐剂是基于皂苷的佐剂。本发明提供了一种在受试者中诱导免疫应答的方法，包括向受试者施用有效量的上述疫苗。最后，本发明提供了一种用于治疗受试者的癌症的方法，包括向受试者施用适量的上述疫苗。

60. 发明授权

US07271160B2 Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases 失效
标题翻译：用于降解和/或抑制HER-家族酪氨酸激酶的方法和组合物
公开(公告)号：US07271160B2
公开(公告)日：2007-09-18
申请号：US09960665
申请日：2001-09-21
申请人： Neal Rosen , Scott D. Kuduk , Samuel J. Danishefsky , Furzhong F. Zheng , Laura Sepp-Lorenzino , Ouatek Ouerfelli
发明人： Neal Rosen , Scott D. Kuduk , Samuel J. Danishefsky , Furzhong F. Zheng , Laura Sepp-Lorenzino , Ouatek Ouerfelli
IPC分类号： C07D403/02 , A61K31/395 , A61P35/00
CPC分类号： C07D225/06 , A61K47/55
摘要： Bifunctional molecules comprising two hsp-binding moieties which bind to hsp90 in the pocket to which ansamycin antibiotics bind connected via a linker are effective for inducing the degradation and/or inhibition of HER-family tyrosine kinases. For example, a compound of two geldanamycin moities joined by a four-carbon linker provides selective degradation of HER-family tyrosine kinases, without substantially affecting other kinases. These compounds can be used for treatment of HER-positive cancers with reduced toxicity, since these compounds potently kill cancer cells but affect fewer proteins than geldanamycin.
摘要翻译：包含两个hsp结合部分的双功能分子对于诱导HER-家族酪氨酸激酶的降解和/或抑制是有效的，所述hsp结合部分与口服中与安莎霉素抗生素通过接头连接的hsp90结合。例如，通过四碳连接物连接的两个格尔德霉素系的化合物提供HER-家族酪氨酸激酶的选择性降解，而基本上不影响其它激酶。这些化合物可用于治疗具有降低毒性的HER阳性癌症，因为这些化合物有效杀死癌细胞，但影响比格尔德霉素少的蛋白质。

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