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1. 发明授权

US4954637A Certain maleimide-N-alkylenecarboxylate-ortho-nitrobenzenesulfonic acid esters and derivatives useful for coupling biological materials 失效
标题翻译：某些马来酰亚胺-N-亚烷基羧酸酯 - 邻硝基苯磺酸酯和衍生物可用于偶联生物材料
公开(公告)号：US4954637A
公开(公告)日：1990-09-04
申请号：US95325
申请日：1987-09-10
申请人： Danute E. Nitecki , Lois Aldwin
发明人： Danute E. Nitecki , Lois Aldwin
IPC分类号： C07D211/54 , C07D213/70 , C07K1/00 , C07K1/10
CPC分类号： C07D213/70 , C07D211/54 , C07K1/003 , C07K1/006 , C07K1/10
摘要： Coupling of biological materials is disclosed via 4-hydroxy-3-nitrobenzene sulfonic acid sodium salt (HNSA) esters. The novel activated esters are structured so as to react at one end with an amine group of a selected biological or non-biological material, thereby releasing the spectroscopically monitorable HNSA dianion, and at the other end with, typically, a sulfhydryl group of a second material which may or may not be biological. The esters provide for a cross-linking reaction that may be easily controlled and monitored.
摘要翻译：通过4-羟基-3-硝基苯磺酸钠盐（HNSA）酯公开生物材料的偶联。所述新型活化酯的结构使其在一端与选定的生物或非生物材料的胺基反应，由此释放可光谱监测的HNSA二价阴离子，另一端通常具有二硫代基可能是或可能不是生物的材料。这些酯提供可以容易地控制和监测的交联反应。

2. 发明授权

US4895872A Immunosupressive analogues and derivatives of succinylacetone 失效
标题翻译：琥珀酰丙酮的免疫抑制类似物和衍生物
公开(公告)号：US4895872A
公开(公告)日：1990-01-23
申请号：US324360
申请日：1989-03-15
申请人： Danute E. Nitecki , Margaret Moreland , Lois Aldwin , Corey H. Levenson , Irwin Braude , David F. Mark , Henry Rapaport
发明人： Danute E. Nitecki , Margaret Moreland , Lois Aldwin , Corey H. Levenson , Irwin Braude , David F. Mark , Henry Rapaport
IPC分类号： A61K31/12 , A61K31/16 , A61K31/19 , A61K31/22 , A61K31/23 , A61K31/41
CPC分类号： A61K31/41 , A61K31/12 , A61K31/16 , A61K31/19 , A61K31/22 , A61K31/23
摘要： Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要翻译：所示的琥珀酰丙酮衍生物或相关药物及其合成方法，其中药物由琥珀酰丙酰基 - 脯氨酸-PEG，琥珀酰乙酰基-NH- PEG或具有下式的化合物组成：其中n = 1-6。基于它们在细胞免疫测定中的活性和大鼠中的佐剂诱导的关节炎的活性，分别在体内和体外具有免疫抑制活性。

3. 发明授权

US4894226A Solubilization of proteins for pharmaceutical compositions using polyproline conjugation 失效
标题翻译：使用聚脯氨酸共轭对药物组合物进行蛋白质的溶解
公开(公告)号：US4894226A
公开(公告)日：1990-01-16
申请号：US931197
申请日：1986-11-14
申请人： Lois Aldwin , Danute E. Nitecki
发明人： Lois Aldwin , Danute E. Nitecki
IPC分类号： A61K38/00 , A61K47/00 , A61K47/48 , C07K1/107 , C07K14/52 , C07K17/00 , C12P21/02
CPC分类号： C07K1/1075 , A61K47/48315 , C07K14/52 , A61K38/00
摘要： A pharmaceutical composition is prepared wherein a biologically active conjugated protein is dissolved in an aqueous carrier medium in the absence of a solubilizing agent. The unconjugated protein, which is not readily water-soluble at pH 6-8 without such solubilizing agent, is covalently conjugated to polyproline via a flexible spacer arm and exhibits substantial biological activity.
摘要翻译：制备药物组合物，其中在没有增溶剂的情况下将生物活性的缀合蛋白溶解在含水载体介质中。没有这种增溶剂在pH6-8下不容易水溶的非共轭蛋白质通过柔性间隔臂与多脯氨酸共价共轭并表现出显着的生物学活性。

4. 发明授权

US5252603A Immunosuppressive analogues and derivatives of succinylacetone 失效
标题翻译：琥珀酰丙酮的免疫抑制类似物和衍生物
公开(公告)号：US5252603A
公开(公告)日：1993-10-12
申请号：US623096
申请日：1990-12-06
申请人： Danute E. Nitecki , Lois Aldwin , Corey H. Levenson , Margaret Moreland , Irwin Braude , David F. Mark , Henry Rapoport
发明人： Danute E. Nitecki , Lois Aldwin , Corey H. Levenson , Margaret Moreland , Irwin Braude , David F. Mark , Henry Rapoport
IPC分类号： A61K31/12 , A61K31/16 , A61K31/19 , A61K31/22 , A61K31/23 , A61K31/41 , A61K31/205
CPC分类号： A61K31/19 , A61K31/12 , A61K31/16 , A61K31/22 , A61K31/23 , A61K31/41
摘要： Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## wherein n=1-6R=CH.sub.3, CF.sub.3, --CO.sub.2 R.sup.IV, ##STR2## R.sup.I, R.sup.II =H, F, CH.sub.3, or ##STR3## R.sup.III =H, ##STR4## or tetrazolyl R.sup.IV =H, or alkyland that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要翻译：显示衍生的琥珀酰丙酮衍生的或相关的药物及其合成方法，其中药物由琥珀酰丙酰基 - 脯氨酸-PEG，琥珀酰乙酰基-NH- PEG或具有下式的化合物组成：其中n = 1-6R = CH 3 ，CF3，-CO2RIV，IMA，RI，RII = H，F，CH3或R IMA = H，IMAGE或四唑基RIV = H或烷基，并且在体内和体外均具有免疫抑制活性分别在细胞免疫学测定和佐剂诱导的大鼠关节炎中的活性。

5. 发明授权

US4902502A Preparation of a polymer/interleukin-2 conjugate 失效
标题翻译：聚合物/白介素-2缀合物的制备
公开(公告)号：US4902502A
公开(公告)日：1990-02-20
申请号：US299235
申请日：1989-01-23
申请人： Danute E. Nitecki , Nandini Katre , Robert J. Goodson , Lois Aldwin
发明人： Danute E. Nitecki , Nandini Katre , Robert J. Goodson , Lois Aldwin
IPC分类号： A61K47/48
CPC分类号： A61K47/48215
摘要： The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.
摘要翻译：本发明是一种制备包含生物活性共轭蛋白质的药物组合物的方法。它包含与IL-2缀合的聚乙二醇或聚氧乙烯化多元醇。这种蛋白质被缀合以降低其免疫原性，并增加其溶解度，并增加其体内循环体内的半衰期。

6. 发明授权

US5173482A Immunosuppressive analogues and derivatives of succinylacetone 失效
标题翻译：琥珀酰丙酮的免疫抑制类似物和衍生物
公开(公告)号：US5173482A
公开(公告)日：1992-12-22
申请号：US624078
申请日：1990-12-06
申请人： Danute E. Nitecki , Margaret Moreland , Lois Aldwin , Corey H. Levenson , Irwin Braude , David F. Mark , Henry Rapoport
发明人： Danute E. Nitecki , Margaret Moreland , Lois Aldwin , Corey H. Levenson , Irwin Braude , David F. Mark , Henry Rapoport
IPC分类号： A61K31/12 , A61K31/16 , A61K31/19 , A61K31/22 , A61K31/23 , A61K31/41
CPC分类号： A61K31/22 , A61K31/12 , A61K31/16 , A61K31/19 , A61K31/23 , A61K31/41
摘要： Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要翻译：所示的琥珀酰丙酮衍生物或相关药物及其合成方法，其中药物由琥珀酰丙酰基 - 脯氨酸-PEG，琥珀酰乙酰基-NH- PEG或具有下式的化合物组成：其中n = 1-6。基于它们在细胞免疫测定中的活性和大鼠中的佐剂诱导的关节炎的活性，分别在体内和体外具有免疫抑制活性。

7. 发明授权

US5024834A Thioether linked immunotoxin conjugates 失效
标题翻译：硫醚连接的免疫毒素共轭物
公开(公告)号：US5024834A
公开(公告)日：1991-06-18
申请号：US597081
申请日：1990-10-15
申请人： L. L. Houston , Lois Aldwin , Danute E. Nitecki
发明人： L. L. Houston , Lois Aldwin , Danute E. Nitecki
IPC分类号： A61K47/48
CPC分类号： A61K47/48438 , A61K47/48715
摘要： Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.
摘要翻译：长度约为34个ANGSTROM的异双功能交联剂，其由连接到间隔基团的巯基反应基团组成，间隔基团又连接于活化的羧酸酯基团，其可用于制备有效的抗癌免疫毒素缀合物，优选通过使抗体相关氨基酸与活化的羧酸酯基团组合以形成抗体交联剂复合物，并使抗体交联剂复合物与具有反应性巯基的细胞毒素与交联剂的巯基反应性基团反应，并使用如此制备的缀合物来治疗癌症患者。

8. 发明授权

US4943636A Certain pyridyl-di-sulfide-alkylenecarbonxylate-ortho-nitro-phenylsulfonic acid esters useful for coupling biological materials 失效
标题翻译：用于偶联生物材料的某些吡啶基二硫化物 - 亚烷基碳酸酯 - 邻 - 硝基 - 苯基磺酸酯
公开(公告)号：US4943636A
公开(公告)日：1990-07-24
申请号：US95387
申请日：1987-09-10
申请人： Danute E. Nitecki , Lois Aldwin
发明人： Danute E. Nitecki , Lois Aldwin
IPC分类号： C07D211/54 , C07D213/70 , C07K1/00 , C07K1/10
CPC分类号： C07D213/70 , C07D211/54 , C07K1/003 , C07K1/006 , C07K1/10
摘要： Coupling of biological materials is disclosed via 4-hydroxy-3-nitrobenzene sulfonic acid sodium salt (HNSA) esters. The novel activated esters are structured so as to react at one end with an amine group of a selected biological or non-biological material, thereby releasing the spectroscopically monitorable HNSA dianion, and at the other end with, typically, a sulfhydryl group of a second material which may or may not be biological. The esters provide for a cross-linking reaction that may be easily controlled and monitored.
摘要翻译：通过4-羟基-3-硝基苯磺酸钠盐（HNSA）酯公开生物材料的偶联。所述新型活化酯的结构使其在一端与选定的生物或非生物材料的胺基反应，由此释放可光谱监测的HNSA二价阴离子，另一端通常具有二硫代基可能是或可能不是生物的材料。这些酯提供可以容易地控制和监测的交联反应。

9. 发明授权

US5663306A Method of conjugating an activated ester to an amine-containing biological material 失效
标题翻译：将活化的酯与含胺生物材料共轭的方法
公开(公告)号：US5663306A
公开(公告)日：1997-09-02
申请号：US95396
申请日：1987-09-10
申请人： Lois Aldwin , Danute E. Nitecki
发明人： Lois Aldwin , Danute E. Nitecki
IPC分类号： A61K47/48 , C07D207/44 , C07D207/452 , G01N33/543 , C07K1/10 , A61K39/44 , G01N33/547
CPC分类号： C07D207/452 , A61K47/48384 , G01N33/54353 , Y10S530/807 , Y10S530/81 , Y10S530/816
摘要： A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials. An immunotoxin for therapeutic use can be prepared by conjugating the coupling agent to an antibody such as a monoclonal antibody with tumor cell specificity and then joining the resultant conjugate to a cytotoxic molecule.
摘要翻译：通过使4-羟基-3-硝基苯磺酸钠盐（HNSA）与羧酸部分的反应形成N-二异氰酸基-6-氨基己酰基-HNSA（mal-sac-HNSA）等活性酯的偶联剂化合物如N-马来酰亚胺基-6-氨基己酸。偶联剂与pH为5.5〜10.0左右的含胺生物材料如蛋白质的氨基反应，释放HNSA。释放的HNSA在约350nm至约500nm的波长处进行光谱测量，以精确监测和控制偶联剂与生物材料的缀合。将所得产物偶联至巯基或其它另一组材料以提供两者之间的交联。这使得能够将生物材料彼此连接，支撑基质，标签，半抗原和其他材料。用于治疗用途的免疫毒素可以通过将偶联剂与具有肿瘤细胞特异性的抗体（例如单克隆抗体）缀合，然后将所得缀合物连接到细胞毒性分子来制备。

10. 发明授权

US5216005A Immunosuppressive analogues and derivatives of succinylacetone 失效
标题翻译：琥珀酰丙酮的免疫抑制类似物和衍生物
公开(公告)号：US5216005A
公开(公告)日：1993-06-01
申请号：US623095
申请日：1990-12-06
申请人： Danute E. Nitecki , Lois Aldwin , Corey H. Levenson , Margaret Moreland , Irwin Braude , David F. Mark , Henry Rapoport
发明人： Danute E. Nitecki , Lois Aldwin , Corey H. Levenson , Margaret Moreland , Irwin Braude , David F. Mark , Henry Rapoport
IPC分类号： A61K31/12 , A61K31/16 , A61K31/19 , A61K31/22 , A61K31/23 , A61K31/41
CPC分类号： A61K31/16 , A61K31/12 , A61K31/19 , A61K31/22 , A61K31/23 , A61K31/41
摘要： Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要翻译：所示的琥珀酰丙酮衍生物或相关药物及其合成方法，其中药物由琥珀酰丙酰基 - 脯氨酸-PEG，琥珀酰乙酰基-NH- PEG或具有下式的化合物组成：其中n = 1-6。基于它们在细胞免疫测定中的活性和大鼠中的佐剂诱导的关节炎的活性，分别在体内和体外具有免疫抑制活性。

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