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1. 发明授权

US08906355B2 Synthetic stereoisomer peptides in the retro-inverso and inverso configuration, and with cyclic and linear structure, their polymer conjugates, their encapsulation in polymer particles, and uses thereof 有权
标题翻译：合成立体异构体肽具有反向和反转构型，并具有环状和线性结构，它们的聚合物共轭物，它们在聚合物颗粒中的包封及其用途
公开(公告)号：US08906355B2
公开(公告)日：2014-12-09
申请号：US13732951
申请日：2013-01-02
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： A61K31/74 , A61K47/48 , C08G63/48 , C08G63/91 , C08L89/00 , C07K17/08 , C08F222/38 , C07K7/64 , C12N9/96 , C07K7/06 , C07K7/08 , A61K38/00
CPC分类号： C08G63/912 , A61K38/00 , A61K47/58 , A61K47/593 , C07K7/06 , C07K7/08 , C07K7/64 , C07K17/08 , C07K2319/33 , C08F222/38 , C12N9/96 , Y02A50/411
摘要： This invention discloses ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a plurality of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, or disrupt, simultaneously and independently, the functional domain of a different disease causing protein. Therefore the compounds are useful therapeutics for the treatment of abnormal angiogenesis and inflammation which are the hall mark of most human diseases including but not limited to cancer, metastasis, pathological conditions of the eye, cardiovascular, brain, and neurodegenerative disorders, diabetes, and diseases caused by infectious microorganisms.
摘要翻译：本发明公开了包含多个不同的合成和化学修饰的立体异构体肽的配体靶向多立体异构体肽 - 聚合物缀合物化合物，其已经与携带用于靶向递送的肽配体的生物相容性聚合物缀合或包封在配体靶向聚合物纳米颗粒中。立体异构体肽的独特物理化学性质为治疗化合物提供了理想的生物药物特性。由聚合物携带的立体异构体肽被递送至细胞或组织以同时且独立地抑制，抑制或阻断不同疾病引起的蛋白质的功能结构域。因此，这些化合物是用于治疗异常血管发生和炎症的有用治疗剂，其是大多数人类疾病的标志，包括但不限于癌症，转移，眼睛病理状况，心血管，脑和神经变性疾病，糖尿病和疾病由传染性微生物引起。

2. 发明授权

US08715986B2 Stereoisomer peptides, ligand-targeted multi- stereoisomer peptide polymer conjugates, and uses thereof 有权
标题翻译：立体异构体肽，配体靶向多立体异构体肽聚合物缀合物及其用途
公开(公告)号：US08715986B2
公开(公告)日：2014-05-06
申请号：US12914050
申请日：2010-10-28
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： C12N9/96 , A61K38/00 , C07K1/00 , C07K14/00 , C07K17/00 , A61K38/24 , A61K38/27 , C07K16/00 , C08H1/00
CPC分类号： C12N9/96 , A61K47/58 , C07K2319/33
摘要： The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases. Examples of such diseases in human patients include abnormal angiogenesis, pathological conditions of the eye, cancer, metastasis, diabetes, Alzheimer's and Parkinson's diseases, brain and neurodegenerative disorders, bipolar disorder, and diseases caused by aging and pathogen agents, to name a few.
摘要翻译：本发明提供式Poly-（[SP-LI] n -PL-L2）的化合物，其包括152个可用于产生化合物的肽的集合，以及它们用于治疗各种哺乳动物疾病的用途。该化合物，一种新的配体靶向多立体异构体肽聚合物缀合物，包含两个或更多个立体异构体肽和通过接头与生物相容的亲水聚合物（优选HPMA）缀合的肽 - 配体。携带立体异构体肽和肽 - 配体的化合物的稳定性和溶解度的提高提供了理想的药物性质，包括聚合物将肽递送到靶细胞中。本发明的化合物是治疗多种哺乳动物疾病的有用治疗剂。人类患者中的这些疾病的例子包括异常血管发生，眼病理状况，癌症，转移，糖尿病，阿尔茨海默氏症和帕金森病，脑和神经变性疾病，双相性精神障碍以及老化和病原体引起的疾病。

3. 发明授权

US09790286B2 Stereoisomer peptides, their polymer conjugates, their encapsulation into nanoparticles, and uses thereof for the treatment of diseases caused by abnormal angiogenesis 有权
公开(公告)号：US09790286B2
公开(公告)日：2017-10-17
申请号：US14521600
申请日：2014-10-23
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： C07K17/08 , A61K47/48 , C07K7/06 , C07K7/08 , C07K7/64 , C08F222/38 , C08G63/91 , C12N9/96 , A61K38/00
CPC分类号： C07K17/08 , A61K38/00 , A61K47/58 , A61K47/59 , A61K47/593 , C07K7/06 , C07K7/08 , C07K7/64 , C07K2319/33 , C08F222/38 , C08G63/912 , C12N9/96 , Y02A50/411
摘要： This invention discloses the creation of a novel single ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a group of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery and/or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, antagonize or disrupt, simultaneously and independently, the functional domain of different disease causing proteins. Therefore the compounds are novel therapeutics for the treatment of abnormal angiogenesis and inflammation which are the hall mark of most human diseases including but not limited to all cancers, metastasis, eye retinopathies, cardiovascular, brain, and neurodegenerative disorders, diabetes, and diseases caused by infectious microorganisms including virus, bacteria, fungi, and parasites.

4. 发明申请

US20130156723A1 SYNTHETIC STEREOISOMER PEPTIDES IN THE RETRO-INVERSO AND INVERSO CONFIGURATION, AND WITH CYCLIC AND LINEAR STRUCTURE, THEIR POLYMER CONJUGATES, THEIR ENCAPSULATION IN POLYMER PARTICLES, AND USES THEREOF 有权
标题翻译：反相器和反相器配置中的合成立体异构体，以及循环和线性结构，聚合物共聚物，聚合物颗粒中的包封及其用途
公开(公告)号：US20130156723A1
公开(公告)日：2013-06-20
申请号：US13732951
申请日：2013-01-02
申请人： LUCIA IRENE GONZALEZ
发明人： LUCIA IRENE GONZALEZ
IPC分类号： C08G63/91 , C08F222/38
CPC分类号： C08G63/912 , A61K38/00 , A61K47/58 , A61K47/593 , C07K7/06 , C07K7/08 , C07K7/64 , C07K17/08 , C07K2319/33 , C08F222/38 , C12N9/96 , Y02A50/411
摘要： This invention discloses ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a plurality of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, or disrupt, simultaneously and independently, the functional domain of a different disease causing protein. Therefore the compounds are useful therapeutics for the treatment of abnormal angiogenesis and inflammation which are the hall mark of most human diseases including but not limited to cancer, metastasis, pathological conditions of the eye, cardiovascular, brain, and neurodegenerative disorders, diabetes, and diseases caused by infectious microorganisms.
摘要翻译：本发明公开了包含多个不同的合成和化学修饰的立体异构体肽的配体靶向多立体异构体肽 - 聚合物缀合物化合物，其已经与携带用于靶向递送的肽配体的生物相容性聚合物缀合或包封在配体靶向聚合物纳米颗粒中。立体异构体肽的独特物理化学性质为治疗化合物提供了理想的生物药物特性。由聚合物携带的立体异构体肽被递送至细胞或组织以同时且独立地抑制，抑制或阻断不同疾病引起的蛋白质的功能结构域。因此，这些化合物是用于治疗异常血管发生和炎症的有用治疗剂，其是大多数人类疾病的标志，包括但不限于癌症，转移，眼睛病理状况，心血管，脑和神经变性疾病，糖尿病和疾病由感染性微生物引起。

5. 发明申请

US20150050351A1 STEREOISOMER PEPTIDES, THEIR POLYMER CONJUGATES, THEIR ENCAPSULATION INTO NANOPARTICLES, AND USES THEREOF FOR THE TREATMENT OF DISEASES CAUSED BY ABNORMAL ANGIOGENESIS. 审中-公开
标题翻译： STEREOISOMER PEPTIDES，THE POLYMER CONJUGATES，他们纳入纳豆药物及其用于治疗由异常血管生成引起的疾病的用途。
公开(公告)号：US20150050351A1
公开(公告)日：2015-02-19
申请号：US14521600
申请日：2014-10-23
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： C07K17/08 , A61K47/48
CPC分类号： C07K17/08 , A61K38/00 , A61K47/58 , A61K47/59 , A61K47/593 , C07K7/06 , C07K7/08 , C07K7/64 , C07K2319/33 , C08F222/38 , C08G63/912 , C12N9/96 , Y02A50/411
摘要： This invention discloses the creation of a novel single ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a group of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery and/or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, antagonize or disrupt, simultaneously and independently, the functional domain of different disease causing proteins. Therefore the compounds are novel therapeutics for the treatment of abnormal angiogenesis and inflammation which are the hall mark of most human diseases including but not limited to all cancers, metastasis, eye retinopathies, cardiovascular, brain, and neurodegenerative disorders, diabetes, and diseases caused by infectious microorganisms including virus, bacteria, fungi, and parasites.
摘要翻译：本发明公开了一种新型单配体靶向多立体异构体肽 - 聚合物缀合物化合物的制备，其包含一组不同的合成和化学修饰的立体异构体肽，其已经与携带用于靶向递送和/或包封的肽配体的生物相容性聚合物缀合在配体靶向聚合物纳米颗粒中。立体异构体肽的独特物理化学性质为治疗化合物提供了理想的生物药物特性。由聚合物携带的立体异构体肽被递送到细胞或组织以抑制，抑制，阻断，拮抗或破坏不同疾病引起的蛋白质的功能结构域。因此，这些化合物是用于治疗异常血管生成和炎症的新型治疗剂，其是大多数人类疾病的标志，包括但不限于所有癌症，转移，眼视网膜病，心血管，脑和神经变性疾病，糖尿病和由感染性微生物包括病毒，细菌，真菌和寄生虫。

6. 发明授权

US08715685B2 Stereoisomer peptides and their polymer conjugates for HIV disease 有权
标题翻译：立体异构体肽及其用于HIV疾病的聚合物缀合物
公开(公告)号：US08715685B2
公开(公告)日：2014-05-06
申请号：US12836187
申请日：2010-07-14
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： C07K4/02 , C07K7/00 , C07K7/02 , C07K7/50 , C07K11/02 , C07K14/16 , C07K17/08
CPC分类号： A61K38/16 , A61K39/12 , A61K39/21 , A61K2039/6093 , C12N2740/16134
摘要： This invention discloses a group of 298 peptides from which several peptides are independently selected and synthesized in their stereoisomer and chemically modified forms, and conjugated to a polymer via linkers creating novel anti-HIV-1 multi-peptide-polymer conjugate compounds for the treatment and prevention of HIV-1 infection. The peptides mimic the domains of major HIV-1 proteins, and therefore, they function as inhibitors of the targeted HIV-1 proteins. The polymer is a useful delivery system for the stereoisomer peptides, and certain peptides are peptide-ligands for targeted delivery into the HIV infected cells.
摘要翻译：本发明公开了一组298个肽，其中多个肽以其立体异构体和化学修饰形式独立地选择和合成，并通过接头与聚合物缀合，产生新的抗HIV-1多肽 - 聚合物缀合物化合物用于治疗和预防HIV-1感染。肽模拟主要HIV-1蛋白的结构域，因此它们作为靶向HIV-1蛋白的抑制剂起作用。聚合物是用于立体异构体肽的有用的递送系统，并且某些肽是用于靶向递送到HIV感染细胞中的肽配体。

7. 发明申请

US20110104783A1 STEREOISOMER PEPTIDES, LIGAND-TARGETED MULTI- STEREOISOMER PEPTIDE POLYMER CONJUGATES, AND USES THEREOF 有权
标题翻译：立体异构体肽，多重定向多立体聚合物聚合物共聚物及其用途
公开(公告)号：US20110104783A1
公开(公告)日：2011-05-05
申请号：US12914050
申请日：2010-10-28
申请人： LUCIA IRENE GONZALEZ
发明人： LUCIA IRENE GONZALEZ
IPC分类号： C12N9/96 , C07K17/08
CPC分类号： C12N9/96 , A61K47/58 , C07K2319/33
摘要： The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases. Examples of such diseases in human patients include abnormal angiogenesis, pathological conditions of the eye, cancer, metastasis, diabetes, Alzheimer's and Parkinson's diseases, brain and neurodegenerative disorders, bipolar disorder, and diseases caused by aging and pathogen agents, to name a few.
摘要翻译：本发明提供式Poly-（[SP-LI] n -PL-L2）的化合物，其包括152个可用于产生化合物的肽的集合，以及它们用于治疗各种哺乳动物疾病的用途。该化合物，一种新的配体靶向多立体异构体肽聚合物缀合物，包含两个或更多个立体异构体肽和通过接头与生物相容的亲水聚合物（优选HPMA）缀合的肽 - 配体。携带立体异构体肽和肽 - 配体的化合物的稳定性和溶解度的提高提供了理想的药物性质，包括聚合物将肽递送到靶细胞中。本发明的化合物是治疗多种哺乳动物疾病的有用治疗剂。人类患者中的这些疾病的例子包括异常血管发生，眼病理状况，癌症，转移，糖尿病，阿尔茨海默氏症和帕金森病，脑和神经变性疾病，双相性精神障碍以及老化和病原体引起的疾病。

8. 发明申请

US20110014222A1 Stereoisomer Peptides and Their Polymer Conjugates for HIV Disease 有权
标题翻译：立体异构体肽及其用于HIV疾病的聚合物缀合物
公开(公告)号：US20110014222A1
公开(公告)日：2011-01-20
申请号：US12836187
申请日：2010-07-14
申请人： Lucia Irene Gonzalez
发明人： Lucia Irene Gonzalez
IPC分类号： A61K39/21 , C07K7/06 , C12N9/96 , C40B40/10 , C12N5/02 , A61P31/18
CPC分类号： A61K38/16 , A61K39/12 , A61K39/21 , A61K2039/6093 , C12N2740/16134
摘要： The invention relates to a library of 298 peptides useful for formulating a novel therapeutic HIV vaccine. The peptide sequences were selected on the basis of calibration of molecular structure properties of HIV-1 or host cell proteins. A mixture of D- and L-amino acids or all D-amino acids are used to synthesize the stereoisomer peptides for the purpose of increasing their stability. The peptides are expected to have the ability to potently inhibit functioning of proteins important for HIV infection. A plural of the peptides are conjugated together with a biocompatible polymer, preferably HPMA to further increase stability and solubility, decrease drug toxicity, and potentially evade multidrug resistance and exert cooperative effect, since some peptides are the ligands for host proteins such as integrin, trombospondin, VEGFR and LEDGF which can bring the therapeutic peptides to the target cells and therefore help disrupt the interactions between the host proteins and the HIV proteins.
摘要翻译：本发明涉及可用于制备新的治疗性HIV疫苗的298种肽的文库。基于HIV-1或宿主细胞蛋白的分子结构特性的校准来选择肽序列。为了提高其稳定性，使用D-和L-氨基酸或所有D-氨基酸的混合物合成立体异构体肽。肽预期具有有效抑制HIV感染重要蛋白功能的能力。许多肽与生物相容性聚合物（优选HPMA）共轭，以进一步增加稳定性和溶解性，降低药物毒性，并且潜在地逃避多药耐药性并发挥协同作用，因为一些肽是宿主蛋白的配体，例如整联蛋白，反应蛋白，VEGFR和LEDGF，其可以将治疗性肽带到靶细胞，并因此有助于破坏宿主蛋白质与HIV蛋白质之间的相互作用。

9. 发明授权

US06936437B2 Methods and compositions for production of recombinant peptides 失效
标题翻译：用于生产重组肽的方法和组合物
公开(公告)号：US06936437B2
公开(公告)日：2005-08-30
申请号：US10080919
申请日：2002-02-22
申请人： Lucia Irene Gonzalez-Villasenor
发明人： Lucia Irene Gonzalez-Villasenor
IPC分类号： C07K1/113 , C07K14/47 , C12P21/02 , C12P21/06 , C07K1/00 , C07K14/00 , C07K17/00 , C12P21/04
CPC分类号： C07K14/4716 , C07K1/113 , C12P21/02
摘要： This invention provides a method for solubilizing and recovering in bioactive form, a target polypeptide or protein that has been expressed from a host organism in insoluble form. The polypeptide is isolated from the host organism by standard procedures including disrupting the host cell to produce a lysate and recovering the precipitate from the lysate. The precipitate containing the polypeptide is solubilized in a non-denaturant and detergent free non-buffered solubilization solution containing sodium hydroxide between 8 and 10 mM, mannitol between 2 and 5 mM and lactose between 1 and 2 mM. The resultant solubilization preparation contains a biologically active target polypeptide between 1 and 4 mg per ml of solubilization solution. The solubilized polypeptide obtained in this particular manner constitutes the object of the invention. The bioactive solubilized polypeptide is then transferred into an appropriate buffered solution of the desired pH and purified following conventional chromatographic procedures.
摘要翻译：本发明提供一种以生物活性形式溶解和回收的方法，所述方法是从宿主生物以不溶形式表达的靶多肽或蛋白质。通过标准方法从宿主生物体分离多肽，包括破坏宿主细胞以产生裂解物并从裂解物中回收沉淀物。将含有多肽的沉淀溶解在含有8-10mM的氢氧化钠，2至5mM的甘露醇和1至2mM的乳糖的非变性和无去污剂的非缓冲溶解溶液中。所得的溶解制剂含有1至4mg / ml溶解溶液的生物活性目标多肽。以该特定方式获得的增溶多肽构成本发明的目的。然后将生物活性溶解的多肽转移到所需pH的适当缓冲溶液中，并按照常规色谱方法纯化。

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