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1. 发明授权

US10179164B2 Method for inducing an immune response for treatment of cancer and autoimmune diseases or conditions 有权
公开(公告)号：US10179164B2
公开(公告)日：2019-01-15
申请号：US14122240
申请日：2012-05-24
申请人： Daniel H. Zimmerman , Eyal Talor , Kenneth Rosenthal
发明人： Daniel H. Zimmerman , Eyal Talor , Kenneth Rosenthal
IPC分类号： A61K38/00 , A61K39/00 , A61K38/16 , A61K35/12 , A61K51/02 , A61K47/64 , A61K47/68 , A61K47/69
摘要： The invention is related to peptide constructs, i.e., polypeptides obtained by linking together two or more peptides based on or derived from different molecules, which are useful in the treatment or prevention of cancer or the treatment of autoimmune diseases and compositions containing same, methods for producing same, and methods for using same; wherein the peptide constructs have the formula P1-x-P2 where P2 is a peptide associated with forms of cancer or an autoimmune condition and P1 is a peptide which will bind to a class of immune cells such as dendritic cells. The peptide construct can cause the maturation of immature dendritic cells to a more mature state. The peptide construct or the more mature dendritic cells can be administered to a subject to a modulate or to initiate an immune response against cancer cells, and can be used with dyes, radioisotopes, or therapeutic agents for detection of the immune target and/or treatment of cancer and autoimmune conditions.

2. 发明授权

US10179174B2 Method for inducing an immune response and formulations thereof 有权
公开(公告)号：US10179174B2
公开(公告)日：2019-01-15
申请号：US14122238
申请日：2012-05-24
申请人： Daniel H. Zimmerman , Eyal Talor , Kanta Subbarao , Kobporn Boonnak
发明人： Daniel H. Zimmerman , Eyal Talor , Kanta Subbarao , Kobporn Boonnak
IPC分类号： A61K39/00 , A61K39/395 , A61K39/145 , A61K39/385 , A61K38/00 , A61K47/48 , A61K39/12 , C07K14/005 , A61K47/65 , A61K47/64 , A61K47/68
摘要： The invention is related to peptide constructs, i.e., polypeptides obtained by linking together two or more peptides based on or derived from different molecules, which are useful in the treatment or prevention of influenza virus and other infectious diseases. Compositions containing the same, methods for producing the same, and methods for using the same are also disclosed, wherein the peptide constructs have the formula P1-x-P2, where P2 is a peptide associated with an infectious agent and P1 is a peptide that will bind to a class of immune cells, such as dendritic cells. The peptide construct can cause the maturation of immature dendritic cells to a more mature state. The peptide construct or the more mature dendritic cell can be administered to a subject to modulate or initiate an immune response against an infectious agent. Dyes, radioisotopes, or therapeutic agents conjugated with the dendritic cells can be used for localization of the immune target and/or prophylactic or therapeutic treatment of the disease.

3. 发明申请

US20160158330A1 METHODS OF PREPARATION AND COMPOSITION OF PEPTIDE CONSTRUCTS USEFUL FOR TREATMENT OF RHEUMATOID ARTHRITIS 审中-公开
标题翻译：用于治疗恶病质性肾炎的肽制剂的制备方法和组合物
公开(公告)号：US20160158330A1
公开(公告)日：2016-06-09
申请号：US14907520
申请日：2014-04-28
申请人： Daniel H. ZIMMERMAN , Roy CARAMBULA , Harold STEINER , Eyal TALOR , Tibor GLANT , Katalin MIKECZ , CEL-SCI CORPORATION
发明人： Daniel H. Zimmerman , Roy Carambula , Harold Steiner , Eyal Talor , Tibor Glant , Katalin Mikecz
IPC分类号： A61K39/00 , C07K7/08 , C12N5/0784 , C07K14/47
CPC分类号： A61K39/0008 , A61K2039/5154 , A61K2039/6031 , A61K2039/64 , C07K7/08 , C07K14/47 , C07K14/4713
摘要： The invention is related to peptide constructs, i.e., polypeptides obtained by linking together two or more peptides based on or derived from different molecules, which are useful in the treatment or prevention of autoimmune diseases, specifically rheumatoid arthritis (RA) and compositions containing same, methods for producing same and methods for using same; wherein the peptide constructs have the formula P1-x-P2 where P1 is a peptide associated with autoimmune disease such as rheumatoid arthritis myocarditis, diabetes, and immune-mediated disease, which binds to an antigen receptor on a set or subset of T cells; P2 is a peptide which will cause a Th2 directed immune response by the set or subset of T cells to which the peptide P1 is attached or which will bind to a T cell receptor which will cause the set or subset of T cells to which the peptide P1 is attached to initiate, but not complete, an immune response causing the set or subset of T cells to undergo immunomodulation including but not restricted to anergy and apoptosis; and x is a direct bond or linker for covalently bonding P1 and P2. Whereas said treatment being of the individual itself or of ex vivo treatment of isolated DC and or with further labeling with drug, dye or radioisotope and administration back into the patient of the activated and possibly modified DCs for detection, identification, localization and treatment thereof.
摘要翻译：本发明涉及肽构建体，即通过将两种或更多种基于或衍生自不同分子的肽连接在一起而获得的多肽，其可用于治疗或预防自身免疫疾病，特别是类风湿性关节炎（RA）和含有它们的组合物，生产方法及使用方法; 其中所述肽构建体具有式P1-x-P2，其中P1是与自身免疫疾病例如类风湿性关节炎心肌炎，糖尿病和免疫介导的疾病相关的肽，其结合T细胞的集合或亚群上的抗原受体; P2是通过肽P1所连接的T细胞的集合或子集引起Th2定向免疫应答的肽，或者将与T细胞受体结合，所述T细胞受体将导致肽 P1附着以引发但不完全的引起T细胞的集合或亚群进行免疫调节的免疫应答，包括但不限于无反应和凋亡; x是用于共价键合P1和P2的直接键或连接体。而所述治疗是个体本身或离体DC的离体处理，或者用药物，染料或放射性同位素进一步标记，并且向患者施用活化和可能改性的DC用于其检测，鉴定，定位和治疗。

4. 发明申请

US20070166279A1 METHOD FOR MODULATING HLA CLASS II TUMOR CELL SURFACE EXPRESSION WITH A CYTOKINE MIXTURE 审中-公开
标题翻译：用细胞因子混合法调节HLA II级肿瘤细胞表面表达的方法
公开(公告)号：US20070166279A1
公开(公告)日：2007-07-19
申请号：US11690673
申请日：2007-03-23
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： A61K38/21 , A61K38/20 , A61K38/19
CPC分类号： A61K38/191 , A61K38/193 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： A method for altering the composition of tumor infiltrating mononuclear cells, increasing CD4+/CD8+ ratio, increasing tumor stroma/epithelial ratio and modulating HLA (Human Leukocyte Antigen) class II expression on a tumor cell surface with a serum-free and mitogen-free mixture having specific cytokine ratios from the group of IL-1β, TNF-α, IFN-γ, GM-CSF, and Interleukin-2 (IL-2) with specific ratios of IL-1β, TNF-α, IFN-γ, GM-CSF to IL-2, respectively. The serum-free and mitogen-free mixtures comprised of cytokine ratios include Leukocyte Interleukin Injection (LI) or Multikine®, which can be further used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.
摘要翻译：一种改变肿瘤浸润性单核细胞组成的方法，增加CD4 + / CD8 +比例，增加肿瘤基质/上皮比例，并用无血清和无丝分裂素混合物在肿瘤细胞表面上调节HLA（人类白细胞抗原）II类表达具有IL-1β，TNF-α，IFN-γ，GM-CSF和白细胞介素-2（IL-2）的特异性比例的IL-1β，TNF-α，IFN-γ，GM -CSF至IL-2。由细胞因子比例组成的无血清和不含丝裂素的混合物包括白细胞白细胞介素注射（LI）或多克隆，其可以进一步单独使用或与其他药物组合用于治疗癌症，从而增加癌症治疗的成功和癌症患者的无病生存。

5. 发明申请

US20080063625A1 Method for Managing Cholesterol with a Serum-Free and Mitogen-Free Cytokine Mixture 审中-公开
标题翻译：用无血清和无丝分裂素细胞因子混合物治疗胆固醇的方法
公开(公告)号：US20080063625A1
公开(公告)日：2008-03-13
申请号：US11572907
申请日：2005-07-29
申请人： Geert Kersten , Eyal Talor
发明人： Geert Kersten , Eyal Talor
IPC分类号： A61K38/19 , A61P3/00 , A61P9/00
CPC分类号： A61K38/191 , A61K38/193 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： Methods for treating or preventing a disease or disorder, for example, cardiovascular disease, dyslipidemia; dyslipoproteinemia; hyperlipidemia; a disorder of glucose metabolism; Syndrome X; a peroxisome proliferator activated receptor-associated disorder; obesity; hypertension; and renal disease with a serum-free and mitogen-free mixture comprised of specific ratios of cytokines IL-1β, TNF-α, IFN-γ and GM-CSF to Interleukin 2 (IL-2) such as Leukocyte Interleukin Injection (LI) or Multikine®.
摘要翻译：用于治疗或预防疾病或病症的方法，例如心血管疾病，血脂异常; 血脂异常高脂血症葡萄糖代谢紊乱; 综合征X; 过氧化物酶体增殖物激活受体相关病症; 肥胖; 高血压; 和含有无细胞和无丝分裂素的混合物的肾脏疾病，其包含特异性比例的细胞因子IL-1β，TNF-α，IFN-γ和GM-CSF与白细胞介素2（IL-2）如白细胞白细胞介素注射液（LI）或Multikine（R）。

6. 发明申请

US20070128698A1 PEPTIDE CONSTRUCTS FOR TREATING AUTOIMMUNE AND RELATED DISEASES 审中-公开
标题翻译：用于治疗自身免疫和相关疾病的肽结构
公开(公告)号：US20070128698A1
公开(公告)日：2007-06-07
申请号：US11625202
申请日：2007-01-19
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： C12P21/06 , C07H21/04 , C07K14/74
CPC分类号： C07K19/00 , A61K38/00 , C07K14/70539
摘要： Conjugated peptides include a first peptide component which is an antigen associated with autoimmune disease, allergy, asthma or transplantation rejection and binds to an antigen-specific receptor on a T cell, and a second peptide component which corresponds to an “antigen presenting molecule” namely, a peptide binding to a T cell surface receptor, which would normally promote T cell activation when the first peptide is bound to its antigen-specific T cell receptor. However, in this invention, the second peptide component has an amino acid sequence which is a modification of an antigen presenting T cell binding peptide, such modification blocking or inhibiting the engagement of receptor sites on the T cell surface (other than the antigen-specific T cell receptor). As a result of the inhibition/blocking, T cell activation is prevented, and is directed through antigen-specific T cell receptor occupation, without T cell activation, leading to antigen-specific T cell anergy and cell death. Administration of the conjugated peptide to an animal, e.g., human, will provide that animal with protection against the disease associated with the first peptide component, resulting from the elimination of the T cells bearing the antigen-specific receptors for that antigenic peptide. The conjugated peptides of this invention provide antigen-specific protection without impairing the immune response to other antigens, including pathogens.
摘要翻译：共轭肽包括与自身免疫性疾病，变态反应，哮喘或移植排斥相关的抗原的第一肽组分和与T细胞上的抗原特异性受体结合的第一肽组分和对应于“抗原呈递分子”的第二肽组分即结合T细胞表面受体的肽，当第一个肽与其抗原特异性T细胞受体结合时通常会促进T细胞激活。然而，在本发明中，第二肽成分具有作为抗原呈递T细胞结合肽的修饰的氨基酸序列，这种修饰阻断或抑制T细胞表面上的受体位点（除抗原特异性 T细胞受体）。作为抑制/阻断的结果，预防T细胞活化，并且通过抗原特异性T细胞受体占据而被引导，没有T细胞活化，导致抗原特异性T细胞无反应性和细胞死亡。向动物（例如人）施用共轭肽将为该动物提供抵抗与第一种肽组分相关的疾病的保护，这是由于消除携带该抗原肽的抗原特异性受体的T细胞而产生的。本发明的缀合肽提供抗原特异性保护，而不损害对包括病原体在内的其它抗原的免疫应答。

7. 发明申请

US20050158275A1 Method of pre-sensitizing cancer prior to treatment with radiation and/or chemotherapy and a novel cytokine mixture 审中-公开
标题翻译：在用放射治疗和/或化学疗法和新型细胞因子混合物治疗之前使癌前病变的方法
公开(公告)号：US20050158275A1
公开(公告)日：2005-07-21
申请号：US11033835
申请日：2005-01-13
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： A61K20060101 , A61K38/19 , A61K38/20 , A61K38/21 , A61K45/00
CPC分类号： A61K38/193 , A61K38/191 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： This invention relates to a breakthrough method for pre-sensitizing cancer prior to a therapeutic treatment such as chemotherapy, radiation therapy or immuno-therapy and a novel cytokine mixture used in the method thereof The cytokine mixture is a serum-free and mitogen-free mixture comprised of specific ratios of cytokines such as IL-1β, TNF-α, IFN-γ and GM-CSF to Interleukin 2 (IL-2), which is effective in inducing cancerous cells to enter a proliferative cell cycle phase thereby increasing their vulnerability to chemotherapy, radiation therapy and immuno-therapy. One such novel cytokine mixture is Multikine®, which can be used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.
摘要翻译：本发明涉及在化疗，放射治疗或免疫治疗之前的治疗性治疗之前预敏化癌症的突破性方法以及用于其方法的新型细胞因子混合物。细胞因子混合物是无血清和无丝分裂剂混合物包括细胞因子如IL-1β，TNF-α，IFN-γ和GM-CSF与白介素2（IL-2）的特异比例，其有效诱导癌细胞进入增殖细胞周期，从而增加其易感性化疗，放射治疗和免疫治疗。一种这样的新型细胞因子混合物是单独使用或与其他药物组合用于治疗癌症，从而增加癌症治疗的成功和癌症患者的无病存活。

8. 发明申请

US20050002896A1 Method of pre-sensitizing cancer prior to treatment with radiation and/or chemotherapy and a novel cytokine mixture 有权
公开(公告)号：US20050002896A1
公开(公告)日：2005-01-06
申请号：US10611914
申请日：2003-07-03
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： A61K20060101 , A61K38/19 , A61K38/20 , A61K38/21 , A61K45/00
CPC分类号： A61K38/193 , A61K38/191 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： This invention relates to a breakthrough method for pre-sensitizing cancer prior to a therapeutic treatment such as chemotherapy, radiation therapy or immuno-therapy and a novel cytokine mixture used in the method thereof. The cytokine mixture is a serum-free and mitogen-free mixture comprised of specific ratios of cytokines such as IL-1β, TNF-α, IFN-γ and GM-CSF to Interleukin 2 (IL-2), which is effective in inducing cancerous cells to enter a proliferative cell cycle phase thereby increasing their vulnerability to chemotherapy, radiation therapy and immuno-therapy. One such novel cytokine mixture is Multikine®, which can be used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.

9. 发明申请

US20060257357A1 Method for modulating HLA class II tumor cell surface expression with a cytokine mixture 审中-公开
标题翻译：用细胞因子混合物调节HLA II类肿瘤细胞表面表达的方法
公开(公告)号：US20060257357A1
公开(公告)日：2006-11-16
申请号：US11125176
申请日：2005-05-10
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： A61K38/20 , A61K38/19
CPC分类号： A61K38/191 , A61K38/193 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： A method for altering the composition of tumor infiltrating mononuclear cells, increasing CD4+/CD8+ ratio, increasing tumor stroma/epithelial ratio and modulating HLA (Human Leukocyte Antigen) class II expression on a tumor cell surface with a serum-free and mitogen-free mixture having specific cytokine ratios from the group of IL-1β, TNF-α, IFN-γ, GM-CSF, and Interleukin-2 (IL-2) with specific ratios of IL-1β, TNF-α, IFN-γ, GM-CSF to IL-2, respectively. The serum-free and mitogen-free mixtures comprised of cytokine ratios include Leukocyte Interleukin Injection (LI) or Multikine®, which can be further used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.
摘要翻译：一种改变肿瘤浸润性单核细胞组成的方法，增加CD4 + / CD8 +比例，增加肿瘤基质/上皮比例，并用无血清和无丝分裂素混合物在肿瘤细胞表面上调节HLA（人类白细胞抗原）II类表达具有IL-1β，TNF-α，IFN-γ，GM-CSF和白细胞介素-2（IL-2）的特异性比例的IL-1β，TNF-α，IFN-γ，GM -CSF至IL-2。由细胞因子比例组成的无血清和不含丝裂素的混合物包括白细胞白细胞介素注射（LI）或多克隆，其可以进一步单独使用或与其他药物组合用于治疗癌症，从而增加癌症治疗的成功和癌症患者的无病生存。

10. 发明授权

US06896879B2 Method of pre-sensitizing cancer prior to treatment with radiation and/or chemotherapy and a novel cytokine mixture 有权
标题翻译：在用放射治疗和/或化学疗法和新型细胞因子混合物治疗之前使癌前病变的方法
公开(公告)号：US06896879B2
公开(公告)日：2005-05-24
申请号：US10611914
申请日：2003-07-03
申请人： Eyal Talor
发明人： Eyal Talor
IPC分类号： A61K20060101 , A61K38/19 , A61K38/20 , A61K38/21 , A61K45/00
CPC分类号： A61K38/193 , A61K38/191 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： This invention relates to a breakthrough method for pre-sensitizing cancer prior to a therapeutic treatment such as chemotherapy, radiation therapy or immuno-therapy and a novel cytokine mixture used in the method thereof. The cytokine mixture is a serum-free and mitogen-free mixture comprised of specific ratios of cytokines such as IL-1β, TNF-α, IFN-γ and GM-CSF to Interleukin 2 (IL-2), which is effective in inducing cancerous cells to enter a proliferative cell cycle phase thereby increasing their vulnerability to chemotherapy, radiation therapy and immuno-therapy. One such novel cytokine mixture is Multikine®, which can be used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.
摘要翻译：本发明涉及在化疗，放射治疗或免疫治疗之前的治疗性治疗之前预敏化癌症的突破性方法和其方法中使用的新型细胞因子混合物。细胞因子混合物是一种无血清和不含丝裂质的混合物，其特征比例包括IL-1β，TNF-α，IFN-γ和GM-CSF与白介素2（IL-2）的特异性比例，其有效诱导癌细胞进入增殖细胞周期阶段，从而增加其对化学疗法，放射治疗和免疫治疗的脆弱性。一种这样的新型细胞因子混合物是单独使用或与其他药物组合用于治疗癌症，从而增加癌症治疗的成功和癌症患者的无病存活。

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