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1. 发明申请

WO0244128A3 SALICYLATE ANALOGS AS INTERLEUKIN-4 ANTAGONISTS 审中-公开
标题翻译：脂质体模拟物作为白细胞介素-4拮抗剂
公开(公告)号：WO0244128A3
公开(公告)日：2003-03-13
申请号：PCT/US0144643
申请日：2001-11-27
申请人： SUNESIS PHARMACEUTICALS INC , BARR KENNETH J , CUNNINGHAM BRIAN C , FLANAGAN WILLIAM MICHAEL , LU WANLI , RAIMUNDO BRIAN C , WAAL NATHAN D , WILKINSON JENNIFER , ZHU JIANG , YANG WENJIN
发明人： BARR KENNETH J , CUNNINGHAM BRIAN C , FLANAGAN WILLIAM MICHAEL , LU WANLI , RAIMUNDO BRIAN C , WAAL NATHAN D , WILKINSON JENNIFER , ZHU JIANG , YANG WENJIN
IPC分类号： A61P19/00 , A61P29/00 , A61P37/00 , C07C65/105 , C07C65/19 , C07C233/87 , C07C235/42 , C07C235/48 , A61K31/166 , A61K31/192
CPC分类号： C07C235/48 , C07C65/105 , C07C65/19 , C07C233/87 , C07C235/42
摘要： Salicycate analogs of formula, methods of making them, pharmaceutical compositions containing them, and methods for their use. The compounds are interleukin-4 antagonists, and are useful for the treatment of asthma and allergies.
摘要翻译：式的脂环类似物，其制备方法，含有它们的药物组合物及其使用方法。化合物是白细胞介素-4拮抗剂，可用于治疗哮喘和过敏。

2. 发明申请

WO1997011178A1 HUMAN GROWTH HORMONE VARIANTS 审中-公开
标题翻译：人类生长激素变异
公开(公告)号：WO1997011178A1
公开(公告)日：1997-03-27
申请号：PCT/US1996014830
申请日：1996-09-20
申请人： GENENTECH, INC. , CUNNINGHAM, Brian, C. , LOWMAN, Henry, B. , WELLS, James, A. , CLARK, Ross, G. , OLSON, Kenneth , FUH, Germaine, G.
发明人： GENENTECH, INC.
IPC分类号： C12N15/18
CPC分类号： C07K14/61 , A61K38/00 , A61K47/60 , C07K2319/00 , Y10S514/866 , Y10S930/12
摘要： Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.
摘要翻译：公开了对生长激素受体具有增强的亲和力的人生长激素变体。还公开了与一种或多种化学基团缀合的人生长激素变体，例如聚（乙二醇），其被认为延长了变体的体内半衰期。

3. 发明申请

WO1995013296A1 RECEPTOR SPECIFIC ATRIAL NATRIURETIC PEPTIDES 审中-公开
标题翻译：受体特异性ATRIAL NATRIURETIC PEPTIDES
公开(公告)号：WO1995013296A1
公开(公告)日：1995-05-18
申请号：PCT/US1994012591
申请日：1994-11-04
申请人： GENENTECH, INC. , LOWE, David , CUNNINGHAM, Brian, C. , OARE, David , McDOWELL, Robert, S. , BURNIER, John
发明人： GENENTECH, INC.
IPC分类号： C07K14/58
CPC分类号： C07K14/58 , A61K38/00
摘要： Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.
摘要翻译：含有各种取代，特别是G16R的人受体选择性心房利钠因子变体对人A受体显示相同的效力和结合亲和力，但对人清除或C-受体的亲和力降低。这些ANF变体具有利钠，利尿和血管舒张活性，但具有增加的代谢稳定性，使其适合于治疗充血性心力衰竭，急性肾衰竭和肾性高血压。

4. 发明申请

WO1992021029A1 SELECTING LIGAND AGONISTS AND ANTAGONISTS 审中-公开
标题翻译：选择配偶激素和拮抗剂
公开(公告)号：WO1992021029A1
公开(公告)日：1992-11-26
申请号：PCT/US1992003743
申请日：1992-05-06
申请人： GENENTECH, INC. , CUNNINGHAM, Brian, C. , DEVOS, Abraham, M. , MULKERRIN, Michael, G. , ULTSCH, Mark , WELLS, James
发明人： GENENTECH, INC.
IPC分类号： G01N33/50
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2267/03 , A61K38/00 , C07K14/505 , C07K14/535 , C07K14/5412 , C07K14/57554 , C07K14/61 , C07K16/2869 , G01N33/74 , G01N2333/61
摘要： We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.
摘要翻译：我们发现生长激素与其受体形成三元复合物，其中激素上的位点1首先与一个受体分子结合，然后激素位点2然后结合另一个受体分子，从而产生1：2复合物。我们认为这种现象由具有相似构象结构的其他配体共享。基于此现象的分析可用于鉴定配体激动剂和拮抗剂。在结构上鉴定了位点1和2，以便于产生三元复合物形成配体的氨基酸序列变体。提供了生长激素，催乳素胎盘乳酸和其他相关配体的新型变体。作为我们用三元复合物研究的结果，我们确定了这些配体的受体的选定抗体能够作为配体激动剂或拮抗剂。描述了抗生长激素受体抗体的新型生长激素和新用途。

5. 发明申请

WO1997008313A1 VARIANTS OF VASCULAR ENDOTHELIAL CELL GROWTH FACTOR, THEIR USES, AND PROCESSES FOR THEIR PORDUCTION 审中-公开
标题翻译：血管内皮细胞生长因子的变异及其使用及其过程
公开(公告)号：WO1997008313A1
公开(公告)日：1997-03-06
申请号：PCT/US1996013621
申请日：1996-08-23
申请人： GENENTECH, INC. , KEYT, Bruce , NGUYEN, Francis, Hung , FERRARA, Napoleone , CUNNINGHAM, Brian, C. , WELLS, James, A. , LI, Bing
发明人： GENENTECH, INC.
IPC分类号： C12N15/12
CPC分类号： C07K14/515 , A61K38/00 , C07K14/52 , G01N33/74 , G01N2500/00
摘要： The present invention involves the preparation of vascular endothelial growth factor (VEGF) variants which provide materials that are selective in respect of binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.
摘要翻译：本发明涉及血管内皮生长因子（VEGF）变体的制备，其提供关于与激酶结构域和FMS样酪氨酸激酶区分别为KDR和FLT-1的结合特性有选择性的材料。相应的KDR和FLT-1受体由VEGF化合物结构域内的相应结构域结合。其变体定义了这两个绑定区域并对其进行了修改，以便引入中断与相应域的绑定的更改。以这种方式，VEGF分子的最终生物学特性被选择性地修饰。

6. 发明申请

WO1992003478A1 METAL ION MEDIATED RECEPTOR BINDING OF POLYPEPTIDE HORMONES 审中-公开
标题翻译：金属离子介导的多肽受体结合
公开(公告)号：WO1992003478A1
公开(公告)日：1992-03-05
申请号：PCT/US1991005856
申请日：1991-08-16
申请人： GENENTECH, INC. , BASS, Steven, H. , CUNNINGHAM, Brian, C. , FUH, Germaine , LOWMAN, Henry, B. , MATTHEWS, David, J. , WELLS, James, A.
发明人： GENENTECH, INC.
IPC分类号： C07K13/00
CPC分类号： C07K14/72 , A61K38/00 , C07K14/57554 , C07K14/61
摘要： Novel methods are disclosed for modulating the action of polypeptide hormones on mammalian cells, organs or whole mammals. Polypeptide hormone action is controlled by effecting the binding specificity of the polypeptide hormone for distinct receptors. The specificity for the receptor is mediated by the ability of a metal ion to complex between the polypeptide hormone and its receptor. Soluble variants of the hormone receptor may be used to modulate the action or serum half-life of the complexed polypeptide hormone. An example of such a polypeptide hormone system is human growth hormone (hGH) wherein receptor specificity is modulated by the metal cofactor zinc. Under low zinc conditions, hGH preferentially binds to human growth hormone receptor or binding protein, under high zinc conditions, hGH preferentially binds to human prolactin receptor or soluble prolactin receptor variants. This is the first indication that a metal ion can mediate a direct interaction between a polypeptide hormone and an extracellular receptor or binding protein.
摘要翻译：公开了用于调节哺乳动物细胞，器官或整个哺乳动物的多肽激素的作用的新方法。多肽激素作用通过影响多种激素对不同受体的结合特异性来控制。受体的特异性是由金属离子在多肽激素及其受体之间复合的能力所介导的。可以使用激素受体的可溶性变体来调节复合多肽激素的作用或血清半衰期。这种多肽激素系统的一个实例是人生长激素（hGH），其中受体特异性被金属辅因子锌调节。在低锌条件下，hGH优先与人生长激素受体或结合蛋白结合，在高锌条件下，hGH优先与人催乳素受体或可溶性催乳素受体变体结合。这是金属离子可以介导多肽激素和细胞外受体或结合蛋白之间的直接相互作用的第一个迹象。

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