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1. 发明申请

WO2006076471A3 BNP CONJUGATES AND METHODS OF USE 审中-公开
标题翻译： BNP联合使用和使用方法
公开(公告)号：WO2006076471A3
公开(公告)日：2007-03-22
申请号：PCT/US2006001049
申请日：2006-01-12
申请人： NOBEX CORP , JAMES KENNETH
发明人： JAMES KENNETH
IPC分类号： A61K38/00 , C07K14/47
CPC分类号： C07K14/58 , A61K38/00
摘要： Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of liBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.
摘要翻译：本发明公开了改良的利尿钠化合物及其缀合物。特别地，提供缀合形式的liBNP，其包含至少一个与其连接的修饰部分。修饰的利尿钠化合物缀合物保留刺激cGMP产生，结合NPR-A受体，降低动脉血压的活性，并且在一些实施方案中，与未修饰的对应利钠化合物相比，循环中的半衰期改善。可以将口服，肠胃外，肠内，皮下，肺和静脉内形式的化合物和缀合物制备为用于心脏状况的治疗和/或治疗，特别是充血性心力衰竭。还公开了包含具有各种长度和构型的寡聚结构的修饰部分。还公开了具有不同于天然序列的氨基酸序列的hBNP化合物的类似物。

2. 发明申请

WO2005016240A3 ARYL CARBAMATE OLIGOMERS FOR HYDROLYZABLE PRODRUGS AND PRODRUGS COMPRISING SAME 审中-公开
标题翻译：用于可水解产品的ARYL碳酸酯低聚物和包含其的原料
公开(公告)号：WO2005016240A3
公开(公告)日：2006-09-28
申请号：PCT/US2004015004
申请日：2004-05-06
申请人： NOBEX CORP , EKWURIBE NNOCHIRI N , ODENBAUGH AMY L
发明人： EKWURIBE NNOCHIRI N , ODENBAUGH AMY L
IPC分类号： C07C43/20 , A61K20060101 , C07C43/23 , C07C45/67 , C07C45/71 , C07C47/575 , C07C49/84 , C07C235/48 , C07C259/00 , C07C271/00 , C07C271/22 , C07C271/28
CPC分类号： C07C235/48 , C07C41/16 , C07C41/26 , C07C43/23 , C07C45/673 , C07C45/71 , C07C47/575 , C07C49/84 , C07C271/22 , C07C271/28 , C07K7/02 , C07K7/06 , C07C43/2055
摘要： The present invention provides a compound having a formula: (I) where R 1 is selected from the group consisting of alkyl, -CH 2 (OC 2 H4)OCH 3 , and -(OC 2 H 4 )OCH 3 ; n is 0-4; Olig is an oligomer having a formula (I) where L is a optional linker moiety selected from the group consisting of CH 2 O , CH 2 OX , OX , C(O) , C(O)X, NH , NHC(O) , XNHC(O) , NHC(O)X , C(O)NH , C(O)NHX , and (I), where X is alkyl 1-6 or is not present, Y is N or O or is not present, and R 3 is alkyl 1-6 ; PAG is a linear or branched polyalkylene glycol moiety; R 2 is an alkyl 1-22 capping moiety if X is present or alkyl 2-22 if X is not present; and q is a number from 1 to the maximum number of branches on PAG; and m is 1-5.
摘要翻译：本发明提供具有式（I）的化合物，其中R 1选自烷基，-CH 2（OC 2）（OH）2 H 3 OCH 3，和 - （OC 2 H 4 H）OCH 3。 n为0-4; Olig是具有式（I）的低聚物，其中L是选自CH 2，O，CH 2 OX，OX，C（O）），C（O）X，NH，NHC（O），XNHC（O），NHC（O）X，C（O）NH，C（O）NHX和（I） 1-6或不存在，Y为N或O或不存在，且R 3为烷基。 PAG是直链或支链的聚亚烷基二醇部分; 如果X不存在，则R 2是烷基封端的封端部分，如果不存在X则为烷基2-22。 q是PAG上从1到最大分支数的数字; m为1-5。

3. 发明申请

WO2005094448A8 METHODS AND COMPOSITIONS EMPLOYING 4-AMINOPHENYLACETIC ACID COMPOUNDS 审中-公开
标题翻译：使用4-氨基苯甲酸化合物的方法和组合物
公开(公告)号：WO2005094448A8
公开(公告)日：2006-07-06
申请号：PCT/US2005009325
申请日：2005-03-22
申请人： NOBEX CORP , EKWURIBE NNOCHIRI N , LIDDLE RODGER
发明人： EKWURIBE NNOCHIRI N , LIDDLE RODGER
CPC分类号： A61K31/192 , A61K2300/00
摘要： The invention provides compositions comprising 4-APAA compounds and methods for treating disorders involving inflammation of the digestive system and/or mucosal tissues, such as inflammatory bowel disease. The methods and compositions of the invention also include combinations of 4-APAA compounds and 5-ASA compounds for treatment of such disorders.
摘要翻译：本发明提供了包含4-APAA化合物的组合物和用于治疗涉及消化系统和/或粘膜组织的炎症的疾病的炎症性肠病的方法。本发明的方法和组合物还包括用于治疗这种疾病的4-APAA化合物和5-ASA化合物的组合。

4. 发明申请

WO03022208A3 PHARMACEUTICAL COMPOSITIONS OF INSULIN DRUG-OLIGOMER CONJUGATES AND METHODS OF TREATING DISEASES THEREWITH 审中-公开
标题翻译：胰岛素药物 - 低聚物共轭物的药物组合物及其治疗疾病的方法
公开(公告)号：WO03022208A3
公开(公告)日：2003-09-25
申请号：PCT/US0228429
申请日：2002-09-06
申请人： NOBEX CORP , SOLTERO RICHARD , RADHAKRISHNAN BALASINGHAM , EKWURIBE NNOCHIRI N , REHLAENDER BRUCE , HICKEY ANTHONY , BOVET LI LI
发明人： SOLTERO RICHARD , RADHAKRISHNAN BALASINGHAM , EKWURIBE NNOCHIRI N , REHLAENDER BRUCE , HICKEY ANTHONY , BOVET LI LI
IPC分类号： A61K47/48 , A61K38/28 , C07K14/62
CPC分类号： A61K47/554 , A61K47/542 , A61K47/60 , Y10S514/808
摘要： Pharmaceutical compositions that include an insulin drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The insulin drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating an insulin deficiency in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.
摘要翻译：描述了包含胰岛素药物 - 低聚物缀合物，脂肪酸组分和胆汁盐组分的药物组合物。胰岛素药物共价偶联至寡聚部分。脂肪酸组分和胆汁盐组分以1：5至5：1的重量比存在。还提供了使用这样的药物组合物治疗需要这种治疗的受试者的胰岛素缺陷的方法，以及提供这种药物组合物的方法。

5. 发明申请

WO0218324A3 IMMUNOREGULATORY COMPOUNDS, DERIVATIVES THEREOF AND THEIR USE 审中-公开
标题翻译：免疫测定化合物，其衍生物及其用途
公开(公告)号：WO0218324A3
公开(公告)日：2002-08-29
申请号：PCT/US0126697
申请日：2001-08-28
申请人： NOBEX CORP , EKWURIBE NNOCHIRI N , RIGGS-SAUTHIER JENNIFER
发明人： EKWURIBE NNOCHIRI N , RIGGS-SAUTHIER JENNIFER
IPC分类号： A61P1/04 , A61K31/194 , A61K31/195 , A61K31/196 , A61K31/215 , A61K31/606 , A61P1/00 , A61P29/00 , A61P43/00 , C07C245/08 , A61K31/655
CPC分类号： A61K31/195 , A61K31/196 , A61K31/215 , A61K31/24 , C07C229/42 , C07C245/08 , A61K2300/00
摘要： Compounds are disclosed having the structure of Formula (I), where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is (II), where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or (III), where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. Such compounds may be utilized for the prophylaxis or treatment of various diseases, particularly inflammatory conditions of the GI tract. Methods of treating inflammatory conditions of the GI tract such as inflammatory bowel disease using compounds having the following formula are also disclosed (IV), where R9, R10 and R11 are independently selected from the group consisting of hydrogen and C1 to C4 alkyl, and R12 is selected from the group consisting of hydrogen and -C(O)R13, where R13 is a C1 to C6 alkyl or an aryl group.
摘要翻译：公开了具有式（I）结构的化合物，其中R 1，R 3和R 4独立地为氢或C 1至C 4烷基，R 2为（II），其中R 5选自氢和C 1至C 4烷基或（III），其中R 6，R 7和R 8独立地为氢或C 1至C 4烷基; 或其酯或药理学上可接受的盐。这些化合物可用于预防或治疗各种疾病，特别是GI道的炎性病症。还公开了使用具有下式的化合物治疗胃肠道炎症性疾病如炎症性肠病的方法（Ⅳ），其中R9，R10和R11独立地选自氢和C1至C4烷基，R12 选自氢和-C（O）R 13，其中R 13是C 1至C 6烷基或芳基。

6. 发明申请

WO0141812A2 AMPHIPHILIC POLYMERS AND POLYPEPTIDE CONJUGATES COMPRISING SAME 审中-公开
标题翻译：聚合物和聚合物包含相同的聚合物
公开(公告)号：WO0141812A2
公开(公告)日：2001-06-14
申请号：PCT/US0033592
申请日：2000-12-11
申请人： NOBEX CORP , EKWURIBE NNOCHIRI N
发明人： EKWURIBE NNOCHIRI N
IPC分类号： A61K31/74 , A61K38/00 , A61K47/48 , A61P3/04
CPC分类号： A61K47/60
摘要： Proteins and/or peptides, such as luminal cholecystokinin releasing factor (LCRF), are conjugated with amphiphilic oligomers and polymers. Such conjugates may modulate the pharmacokinetic profile of the proteins and/or peptides, thereby improving their clinical utility. Such conjugates may also stabilize and deliver the proteins and/or peptides, such as LCRF, to receptors in the gut without absorption into the bloodstream.
摘要翻译：蛋白质和/或肽，例如腔内缩胆囊素释放因子（LCRF），与两亲低聚物和聚合物缀合。这样的缀合物可以调节蛋白质和/或肽的药代动力学特征，从而改善其临床效用。这样的缀合物还可以将蛋白质和/或肽（例如LCRF）稳定并递送到肠道中的受体而不吸收到血流中。

7. 发明专利

JP2003113113A MIXTURE OF INSULIN DRUG-OLIGOMER CONJUGATES COMPRISING POLYALKYLENE GLYCOL, USES THEREOF, AND METHODS OF MAKING THE SAME 审中-公开
公开(公告)号：JP2003113113A
公开(公告)日：2003-04-18
申请号：JP2001316998
申请日：2001-10-15
申请人： NOBEX CORP
发明人： EKWURIBE NNOCHIRI N , PRICE CHRISTOPHER H , ANSARI ASLAM M , RADHAKRISHNAN BALASINGAM , ODENBAUGH AMY L
IPC分类号： A61K47/34 , A61K38/28 , A61K45/06 , A61K47/48 , A61P3/10 , C07K14/62
摘要： PROBLEM TO BE SOLVED: To provide a substantially monodispersed mixture of conjugates comprising an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety. SOLUTION: This mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

8. 发明专利

JP2003206236A CONJUGATION-STABILIZED POLYPEPTIDE COMPOSITION 审中-公开
公开(公告)号：JP2003206236A
公开(公告)日：2003-07-22
申请号：JP2002260460
申请日：2002-09-05
申请人： NOBEX CORP
发明人： EKWURIBE NNOCHIRI NKEM
IPC分类号： A61K38/00 , A61K9/107 , A61K9/48 , A61K38/04 , A61K38/095 , A61K38/21 , A61K38/22 , A61K38/23 , A61K38/26 , A61K38/27 , A61K38/28 , A61K38/35 , A61K38/43 , A61K38/44 , A61K38/46 , A61K38/48 , A61K47/48 , A61K49/00 , A61P3/10 , A61P5/50 , C07K1/107 , C07K14/00 , C07K14/62 , C08G65/26 , C08G69/10 , C08G69/40 , C08G81/02 , C08L71/02 , C12N9/96
摘要： PROBLEM TO BE SOLVED: To provide a conjugate of a protein exhibiting a biological action and a medicinal composition containing the conjugate. SOLUTION: This stabilized conjugated peptide complex comprises a peptide stably and conjugatively coupled to one or more polymer molecules which do not exist in nature. The peptide is covalently coupled to one or a plurality of molecules of a polymer containing a hydrophilic component such as a linear polyalkylene glycol as one component. The polymer includes a hydrophobic component. The biologically active component improves resistance in human body to enzymes, compared with a case when alone used. COPYRIGHT: (C)2003,JPO

9. 发明申请

WO2006014549A2 SYNTHEIS OF AZO BONDED IMMUNOREGULATORY COMPOUNDS 审中-公开
标题翻译： AZO结合免疫化合物的合成
公开(公告)号：WO2006014549A2
公开(公告)日：2006-02-09
申请号：PCT/US2005024109
申请日：2005-07-07
申请人： NOBEX CORP , SAUTHIER JENNIFER A RIGGS , EKWURIBE NNOCHIRI N
发明人： SAUTHIER JENNIFER A RIGGS , EKWURIBE NNOCHIRI N
IPC分类号： C07C245/06
CPC分类号： C07C245/08
摘要： Methods are disclosed for preparing compounds of Formula I: where R
摘要翻译：公开了制备式I化合物的方法：其中R

10. 发明申请

WO2004047871A3 MODIFIED NATURETIC COMPOUNDS, CONJUGATES, AND USES THEREOF 审中-公开
标题翻译：改性天然化合物，结合物及其用途
公开(公告)号：WO2004047871A3
公开(公告)日：2005-03-17
申请号：PCT/US0337996
申请日：2003-11-12
申请人： NOBEX CORP
发明人： JAMES KENNETH D , RADHAKRISHNAN BALASINGAM , MALKAR NAVDEEP B , MILLER MARK A , EKWURIBE NNOCHIRI N
IPC分类号： A61K47/48 , C07K14/58 , C07K14/72 , C08G65/329 , A61K38/22 , C08G65/32 , C08G65/333
CPC分类号： C08G65/329 , A61K47/60 , C07K14/58 , C07K14/72 , C08L2203/02
摘要： Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, subcutaneous, and intravenous forms to of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.
摘要翻译：本发明公开了改进的利尿钠化合物及其缀合物。特别地，提供了缀合形式的hBNP，其包括与其连接的至少一个修饰部分。修饰的利尿钠化合物缀合物保留刺激cGMP产生，结合NPR-A受体的活性，并且在一些实施方案中，与未修饰的对应利钠化合物相比，循环中的半衰期改善。可以制备化合物和缀合物的口服，肠胃外，皮下和静脉内形式作为心脏状况的治疗和/或治疗，特别是充血性心力衰竭。还公开了包含具有各种长度和构型的寡聚结构的修饰部分。还公开了利尿钠化合物的类似物，其具有不同于天然序列的氨基酸序列。

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