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1. 发明授权

KR101162908B1 수용체-결합 활성이 보존된, 사이토카인, 케모카인,성장인자, 폴리펩티드 호르몬 및 이들의 길항제의 중합체접합체 有权
标题翻译：细胞因子，化合物，生长因子，多肽HORMONES的聚合物和具有保留的受体结合活性的拮抗剂
公开(公告)号：KR101162908B1
公开(公告)日：2012-07-06
申请号：KR1020057012120
申请日：2003-12-23
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 바스카란,샤이암,에스. , 셔만,메리,알. , 세이퍼,마크,쥐.,피. , 윌리암스,엘.,데이비드
IPC分类号： A61K31/74 , C08G63/48
CPC分类号： A61K38/2013 , A61K38/1808 , A61K38/191 , A61K38/212 , A61K38/30 , A61K47/60 , C07K14/52 , C07K14/521
摘要： Methods are provided for the synthesis of polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and receptor-binding antagonists thereof, which conjugates retain unusually high receptor-binding activity. Preparation of polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of receptor-ligand interactions that commonly results from the attachment of polymers to receptor-binding regions of cytokines, chemokines, growth factors and polypeptide hormones, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods. The conjugates of the present invention retain a higher level of receptor-binding activity than those produced by traditional polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines, chemokines, growth factors and polypeptide hormones. The conjugates of the present invention also exhibit an extended half-life in vivo and in vitro compared to unconjugated cytokines, chemokines, growth factors and polypeptide hormones. The present invention also provides kits comprising such conjugates and/or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic, prophylactic, therapeutic and bioprocessing applications.

2. 发明公开

KR1020050089860A 수용체-결합 활성이 보존된, 사이토카인, 케모카인,성장인자, 폴리펩티드 호르몬 및 이들의 길항제의 중합체접합체 有权
标题翻译：细胞因子，化合物，生长因子，多肽HORMONES的聚合物和具有保留的受体结合活性的拮抗剂
公开(公告)号：KR1020050089860A
公开(公告)日：2005-09-08
申请号：KR1020057012120
申请日：2003-12-23
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 바스카란,샤이암,에스. , 셔만,메리,알. , 세이퍼,마크,쥐.,피. , 윌리암스,엘.,데이비드
IPC分类号： A61K31/74 , C08G63/48
CPC分类号： A61K38/2013 , A61K38/1808 , A61K38/191 , A61K38/212 , A61K38/30 , A61K47/60 , C07K14/52 , C07K14/521
摘要： Methods are provided for the synthesis of polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and receptor-binding antagonists thereof, which conjugates retain unusually high receptor-binding activity. Preparation of polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of receptor-ligand interactions that commonly results from the attachment of polymers to receptor-binding regions of cytokines, chemokines, growth factors and polypeptide hormones, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods. The conjugates of the present invention retain a higher level of receptor-binding activity than those produced by traditional polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines, chemokines, growth factors and polypeptide hormones. The conjugates of the present invention also exhibit an extended half-life in vivo and in vitro compared to unconjugated cytokines, chemokines, growth factors and polypeptide hormones. The present invention also provides kits comprising such conjugates and/or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic, prophylactic, therapeutic and bioprocessing applications.
摘要翻译：提供了用于合成细胞因子，趋化因子，生长因子，多肽激素和其受体结合拮抗剂的聚合物缀合物的方法，该共轭物保留非常高的受体结合活性。根据本发明的方法制备聚合物缀合物减少或避免了通常由聚合物与细胞因子，趋化因子，生长因子和多肽激素的受体结合区附着而引起的受体 - 配体相互作用的空间抑制，以及其激动和拮抗类似物。本发明还提供了通过这些方法制备的缀合物和组合物。本发明的缀合物比没有靶向避免细胞因子，趋化因子，生长因子和多肽激素的受体结合结构域的传统聚合物偶联方法所产生的那些具有更高水平的受体结合活性。与未结合的细胞因子，趋化因子，生长因子和多肽激素相比，本发明的缀合物在体内和体外也表现出延长的半衰期。本发明还提供包含这种缀合物和/或组合物的试剂盒，以及在各种诊断，预防，治疗和生物加工应用中使用这种缀合物和组合物的方法。

3. 发明授权

KR101022577B1 항원성이 감소한 중합체 콘쥬게이트, 이의 제조방법 및용도 有权
标题翻译：聚合物具有降低的抗菌性，其制备方法及其用途
公开(公告)号：KR101022577B1
公开(公告)日：2011-03-16
申请号：KR1020057005504
申请日：2003-09-25
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 마르티네즈,알렉사,엘. , 셔만,메리,알. , 세이퍼,마크,쥐.,피. , 윌리암스,엘.데이비드
IPC分类号： C08G63/91 , A61K38/16 , A61K31/765 , A61K38/19
CPC分类号： A61K47/646 , A61K9/1271 , A61K38/00
摘要： 다양한 생체활성 성분, 특히 단백질의 수용성 중합체 (예를 들면, 폴리(에틸렌 글리콜) 및 이의 유도체)와의 콘쥬게이트의 제조방법이 제공되는데, 여기에서 콘쥬게이트는 메톡실 또는 또다른 알콕실기를 함유하는 폴리(에틸렌 글리콜)을 사용하여 제조된 유사한 콘쥬게이트와 비교하여 감소한 항원성 및 면역원성을 가진다. 본 발명은 또한 이러한 방법에 의해 제조되는 콘쥬게이트, 이러한 콘쥬게이트를 포함하는 조성물, 이러한 콘쥬게이트 또는 조성물을 함유하는 키트 및 진단 및 치료 요법에 있어서 콘쥬게이트와 조성물의 사용방법을 제공한다.
콘쥬게이트, 생체활성 성분, 폴리알킬렌 글리콜

4. 发明授权

KR101238517B1 생물학적 효능이 향상된 인터페론-베타의 중합체 접합체 有权
标题翻译：干扰素与增强生物学特性的聚合物结合
公开(公告)号：KR101238517B1
公开(公告)日：2013-02-28
申请号：KR1020057012126
申请日：2003-12-23
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 세이퍼,마크,쥐.,피. , 마르티네즈,알렉사,엘. , 윌리암스,데이비드,엘. , 셔만,메리,알.
IPC分类号： C07K14/565 , C07K14/52 , A61K38/21
CPC分类号： A61K38/215 , A61K47/60 , C07K14/565 , G01N2333/565
摘要： 사이토카인 및 이들의 수용체-결합성 길항물질, 특히 비당질화된 인터페론-β의 중합체 접합체의 합성 방법이 제공되며, 상기 접합체는 매우 높은 생물학적 효능을 유지한다. 본 발명의 방법에 따른 중합체 접합체의 제조는, 사이토카인의 수용체-결합 영역, 및 이들의 효현 및 길항 유사물질에 대한 중합체의 부착의 결과로 일반적으로 야기되는 수용체-리간드 상호작용의 입체적 억제를 감소 또는 방지한다. 본 발명은 또한, 그러한 방법에 의해 제조된 접합체 및 조성물을 제공한다. 본 발명의 접합체는, 사이토카인의 수용체-결합 영역을 회피하도록 목적되지 않은 종래의 중합체 커플링 방법에 의해 제조된 것보다 높은 수준의 생물학적 효능을 유지한다. 시험관내 검정법에서, 본 발명의 비당질화 인터페론-β의 접합체의 생물학적 효능은 비접합체화된 인터페론-β의 것보다 실질적으로 높으며 당질화 인터페론-β 1a의 것과 유사하다. 본 발명의 접합체는 또한 생체내에서, 대응하는 비접합체화된 사이토카인과 비교할 때 연장된 반감기를 나타낸다. 본 발명은 또한, 그러한 접합체 및(또는) 조성물을 포함하는 키트; 그러한 접합체 및 조성물을, 다발성 경화증의 치료를 포함하는 다양한 진단, 예방, 치료 용도에 사용하는 방법을 제공한다.
인터페론-β, 폴리알킬렌 글리콜, 사이토카인, 접합체

5. 发明公开

KR1020050092022A 생물학적 효능이 향상된 인터페론-베타의 중합체 접합체 有权
标题翻译：干扰素与增强生物学特性的聚合物结合
公开(公告)号：KR1020050092022A
公开(公告)日：2005-09-16
申请号：KR1020057012126
申请日：2003-12-23
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 세이퍼,마크,쥐.,피. , 마르티네즈,알렉사,엘. , 윌리암스,데이비드,엘. , 셔만,메리,알.
IPC分类号： C07K14/565 , C07K14/52 , A61K38/21
CPC分类号： A61K38/215 , A61K47/60 , C07K14/565 , G01N2333/565
摘要： Methods are provided for the synthesis of polymer conjugates of cytokines and receptor-binding antagonists thereof, especially a non glycosylated interferon-beta, which conjugates retain unusually high biological potency. Preparation of polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of receptor-ligand interactions that commonly results from the attachment of polymers to receptor-binding regions of cytokines, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods. The conjugates of the present invention retain a high level of biological potency compared to those produced by traditional polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines. In assays in vitro, the biological potency of the conjugates of non-glycosylated interferon-beta of the present invention is substantially higher than that of unconjugated interferon- beta and is similar to that of interferon-beta-1a that is glycosylated. The conjugates of the present invention also exhibit an extended half-life in vivo compared to the corresponding unconjugated cytokine. The present invention also provides kits comprising such conjugates and/or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic, prophylactic, therapeutic and bioprocessing applications, including treatment of multiple sclerosis.
摘要翻译：提供了用于合成细胞因子和其受体结合拮抗剂的聚合物缀合物的方法，特别是非糖基化的干扰素-β，其结合物保持非常高的生物效力。根据本发明的方法制备聚合物缀合物减少或避免了通常由聚合物连接到细胞因子的受体结合区域以及其激动剂和拮抗性类似物而引起的受体 - 配体相互作用的空间抑制。本发明还提供了通过这些方法制备的缀合物和组合物。与不是为了避免细胞因子的受体结合结构域靶向的传统聚合物偶联方法制备的那些相比，本发明的缀合物保持高水平的生物效力。在体外测定中，本发明的非糖基化干扰素-β的缀合物的生物学效力明显高于未缀合的干扰素-β的生物效力，并且与经糖基化的干扰素-β-1a相似。与相应的未结合的细胞因子相比，本发明的缀合物在体内也表现出延长的半衰期。本发明还提供包含这种缀合物和/或组合物的试剂盒，以及在各种诊断，预防，治疗和生物加工应用中使用这种缀合物和组合物的方法，包括治疗多发性硬化症。

6. 发明公开

KR1020050083702A 항원성이 감소한 중합체 콘쥬게이트, 이의 제조방법 및용도 有权
标题翻译：聚合物具有降低的抗菌性，其制备方法及其用途
公开(公告)号：KR1020050083702A
公开(公告)日：2005-08-26
申请号：KR1020057005504
申请日：2003-09-25
申请人： 마운틴 뷰 파마슈티컬즈, 인크.
发明人： 마르티네즈,알렉사,엘. , 셔만,메리,알. , 세이퍼,마크,쥐.,피. , 윌리암스,엘.데이비드
IPC分类号： C08G63/91 , A61K38/16 , A61K31/765 , A61K38/19
CPC分类号： A61K47/646 , A61K9/1271 , A61K38/00 , C08G65/34 , A61K31/765 , A61K38/16 , A61K38/19 , A61K47/60 , C08G65/48
摘要： Methods are provided for the preparation of conjugates of a variety of bioactive components, especially proteins, with water-soluble polymers (e. g., poly(ethylene glycol) and derivatives thereof), which conjugates have reduced antigenicity and immunogenicity compared to similar conjugates prepared using poly(ethylene glycol) containing a methoxyl or another alkoxyl group. The invention also provides conjugates prepared by such methods, compositions comprising such conjugates, kits containing such conjugates or compositions and methods of use of the conjugates and compositions in diagnostic and therapeutic protocols.
摘要翻译：提供了用于制备各种生物活性组分（特别是蛋白质）与水溶性聚合物（例如聚（乙二醇）及其衍生物）的缀合物的缀合物的方法，该缀合物与使用聚合物制备的类似共轭物相比具有降低的抗原性和免疫原性（乙二醇），其含有甲氧基或其它烷氧基。本发明还提供了通过这种方法制备的缀合物，包含这种缀合物的组合物，含有这种缀合物或组合物的试剂盒以及在诊断和治疗方案中使用缀合物和组合物的方法。

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