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1. 发明申请

WO2005120550A3 A METHOD FOR ALTERING THE CD4/CD8 RATIO AND THE MONONUCLEAR CELLULAR INFILTRATE INTO A TUMOR 审中-公开
标题翻译：将CD4 / CD8比例和单核细胞浸润液转化为肿瘤的方法
公开(公告)号：WO2005120550A3
公开(公告)日：2007-03-22
申请号：PCT/US2005019263
申请日：2005-06-03
申请人： CEL SCI CORP , TALOR EYAL
发明人： TALOR EYAL
IPC分类号： A01N37/18 , A61K38/19 , A61K38/20 , A61K38/21 , A61K39/00
CPC分类号： A61K38/193 , A61K31/5575 , A61K31/558 , A61K38/1808 , A61K38/191 , A61K38/195 , A61K38/20 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K45/06 , A61K2300/00
摘要： A method for altering the CD4/CD8 ratio and the mononuclear cellular infiltrate into a tumor that results in significant modulation of the infiltrating immune cells shown by a decrease in CD8+ T cells and a significant increase in tumor infiltrating CD4+ T cells. A dose of 800 IU/day as IL-2 for 5 days per week for 3 weeks of a Leukocyte Interleukin Injection (LI) being a serum-free and mitogen-free mixture comprised of specific ratios of cytokines IL-1ß, TNF-a, IFN-? and GM-CSF to Interleukin 2 (IL-2) resulted in a paradigm shift. The paradigm shift is defined as a marked CD4+ T cell infiltrate and a clear and specific change in the density and localization of antigen presenting cells such as dendritic cells and inflammatory cells, particularly neutrophils in cancer nests.
摘要翻译：将CD4 / CD8比例和单核细胞浸润转化成肿瘤的方法，其导致CD8 + T细胞减少所示的浸润性免疫细胞的显着调节，以及肿瘤浸润性CD4 + T细胞的显着增加。白细胞白介素注射液（LI）为无血清和无丝分裂剂混合物，每周5天，每周5天，每周5天，剂量为800IU /天，其特征在于细胞因子IL-1β，TNF-α ，IFN- 和GM-CSF与白细胞介素2（IL-2）的结合导致了范式转变。范式转变被定义为显着的CD4 + T细胞浸润，并且抗原呈递细胞如树突状细胞和炎性细胞，特别是癌巢中的嗜中性粒细胞的密度和定位的清晰和特异性变化。

2. 发明申请

WO0143695A3 PEPTIDE CONSTRUCTS FOR TREATING AUTOIMMUNE AND RELATED DISEASES 审中-公开
标题翻译：用于治疗自身免疫性疾病和相关疾病的肽结构
公开(公告)号：WO0143695A3
公开(公告)日：2002-02-21
申请号：PCT/US0041647
申请日：2000-10-27
申请人： CEL SCI CORP , TALOR EYAL I
发明人： TALOR EYAL I
IPC分类号： A61K38/00 , A61P37/06 , A61P37/08 , C07K14/74 , C07K19/00 , C07K14/00 , A61K38/10 , A61K38/16 , A61K38/17 , A61K39/35 , A61K39/385 , C07K17/00
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, 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 will provide protection against 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.
摘要翻译：共轭肽包括与自身免疫疾病，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，其通常促进T细胞活化。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）。结果，T细胞激活被阻止，并且通过抗原特异性T细胞受体占据被引导，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。将缀合肽施用于动物将提供针对与第一种肽组分相关的疾病的保护，这是由于消除具有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，而不损害对其他抗原的免疫应答。

3. 发明申请

WO2012162565A3 METHOD FOR INDUCING AN IMMUNE RESPONSE FOR TREATMENT OF CANCER AND AUTOIMMUNE DISEASES OR CONDITIONS 审中-公开
标题翻译：诱导免疫反应治疗癌症和自身免疫性疾病或病症的方法
公开(公告)号：WO2012162565A3
公开(公告)日：2013-06-13
申请号：PCT/US2012039474
申请日：2012-05-24
申请人： CEL SCI CORP , ZIMMERMAN DANIEL H , TALOR EYAL , ROSENTHAL KENNETH
发明人： ZIMMERMAN DANIEL H , TALOR EYAL , ROSENTHAL KENNETH
IPC分类号： A61K39/395 , A61K38/16 , A61K38/17 , A61P35/00
CPC分类号： A61K39/00 , A61K35/12 , A61K38/162 , A61K39/0008 , A61K39/0011 , A61K47/646 , A61K47/68 , A61K47/6901 , A61K51/02 , A61K2039/5154
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 Pi-x-P2 where P2 is a peptide associated with forms of cancer or an autoimmune condition and Pi 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 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.
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癌症或治疗自身免疫疾病和含有其的组合物，方法生产方法和使用方法; 其中所述肽构建体具有式Pi-x-P2，其中P2是与癌症形式或自身免疫病症相关的肽，并且Pi是将结合一类免疫细胞如树突状细胞的肽。肽结构可导致未成熟树突状细胞的成熟进入更成熟的状态。肽构建体或更成熟的树突细胞可以施用于受试者以调节或引发针对癌细胞的免疫应答，并且可以与染料，放射性同位素或治疗剂一起用于检测免疫靶标和/或治疗癌症和自身免疫病症。

4. 发明申请

WO2006122178A3 A METHOD FOR MODULATING HLA CLASS II TUMOR CELL SURFACE EXPRESSION WITH A CYTOKINE MIXTURE 审中-公开
标题翻译：用于调节细胞因子混合物的HLA II类肿瘤细胞表面表达的方法
公开(公告)号：WO2006122178A3
公开(公告)日：2007-03-29
申请号：PCT/US2006018055
申请日：2006-05-10
申请人： CEL SCI CORP , TALOR EYAL
发明人： TALOR EYAL
IPC分类号： A61K45/00 , A61K38/21
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-I ß, TNF-a, IFN-?, GM-CSF, and Interleukin-2 (IL-2) with specific ratios of IL-I ß, TNF-a, IFN-?, 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 along 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IL-1β，TNF-α，IFN-γ特异性比例的特异性细胞因子比例。，GM-CSF分别为IL-2。由细胞因子比例组成的无血清和无丝分裂原混合物包括白细胞白细胞介素，注射液（LI）或多克隆，可以进一步与其他药物联合使用或与其结合使用，用于治疗癌症，从而增加癌症治疗的成功，癌症患者的无病生存。

5. 发明申请

WO2005007086A3 A 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：辐射和/或化学治疗以及新的细胞因子混合物治疗前预敏化癌症的方法
公开(公告)号：WO2005007086A3
公开(公告)日：2005-07-07
申请号：PCT/US2004020998
申请日：2004-07-01
申请人： CEL SCI CORP , TALOR EYAL
发明人： TALOR EYAL
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-1beta , TNF-alpha, IFN-gamma 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(R), 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：本发明涉及在诸如化学疗法，放射疗法或免疫疗法之类的治疗性治疗之前使癌症前致敏的突破性方法，以及其方法中使用的新型细胞因子混合物。细胞因子混合物是由特定比例的细胞因子如IL-1β，TNF-α，IFN-γ和GM-CSF与白细胞介素2（IL-2）组成的无血清和无丝裂原混合物，其有效诱导癌细胞进入增殖性细胞周期阶段，从而增加它们对化学疗法，放射疗法和免疫疗法的易感性。一种这样的新型细胞因子混合物是Multikine，其可以单独使用或与其他药物组合用于治疗癌症，由此增加癌症治疗的成功和癌症患者的无疾病存活。

6. 发明申请

WO0136448A8 PREPARATION AND COMPOSITION OF PEPTIDES USEFUL FOR TREATMENT OF AUTOIMMUNE AND TRANSPLANT RELATED GRAFT VERSUS HOST CONDITIONS 审中-公开
标题翻译：适用于治疗自身免疫和运输的有用的肽的制备和组合相关的主要病原体
公开(公告)号：WO0136448A8
公开(公告)日：2002-06-20
申请号：PCT/US0041646
申请日：2000-10-27
申请人： CEL SCI CORP , ZIMMERMAN DANIEL H
发明人： ZIMMERMAN DANIEL H
IPC分类号： A61K38/00 , A61P11/06 , A61P37/02 , A61P37/08 , C07K14/00 , C07K14/78 , C07K19/00
CPC分类号： C07K14/78 , A61K38/00 , C07K14/4713
摘要： Peptide constructs including a first peptide segment which includes an amino acid sequence associated with autoimmune disease, asthma, allergy or xeno- or allograft transplantation rejections bonded directly or via a linker or spacer to a second peptide which binds to T cells and which will redirect the immune response from a harmful Th1 response to a less harmful Th2 response, or which will bind to T cells to initiate, but not complete, an immune response causing the T cells to which the first peptide binds, to undergo anergy and apoptosis, are useful in treating autoimmune conditions. For instance, the peptide construct NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK (SEQ ID NO:14) wherein Th2 stimulating Peptide G (SEQ ID NO:15) is covalently linked, via spacer GGG, to cardiac myosin molecule My1 (SEQ ID NO:16), can be used for treatment or prevention of myocarditis.
摘要翻译：包括第一肽段的肽构建体，其包括与自身免疫性疾病，哮喘，变态反应或异种或同种异体移植排斥相关的氨基酸序列，其直接或通过接头或间隔基结合至与T细胞结合的第二肽，并且将重定向有害的Th1应答对不太有害的Th2应答的免疫应答，或者与T细胞结合以引发但不完全的引起第一肽结合的T细胞的免疫应答进行无能和凋亡的免疫应答是有用的在治疗自身免疫性疾病。例如，可以使用其中Th2刺激肽G（SEQ ID NO：15）通过间隔基GGG共价连接到心肌肌球蛋白分子My1（SEQ ID NO：16）的肽构建体NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK（SEQ ID NO：14）用于治疗或预防心肌炎。

7. 发明申请

WO2012082803A3 METHOD FOR INDUCING AN IMMUNE RESPONSE AGAINST AVIAN, SWINE, SPANISH, H1N1, H5N9 INFLUENZA VIRUSES AND FORMULATIONS THEREOF 审中-公开
标题翻译：用于诱导对AVIAN，SWINE，SPANISH，H1N1，H5N9流感病毒及其制剂的免疫应答的方法
公开(公告)号：WO2012082803A3
公开(公告)日：2014-04-10
申请号：PCT/US2011064746
申请日：2011-12-13
申请人： CEL SCI CORP , ZIMMERMAN DANIEL H
发明人： ZIMMERMAN DANIEL H
IPC分类号： A61K39/00
CPC分类号： A61K47/4833 , A61K39/12 , A61K39/145 , A61K45/06 , A61K47/646 , A61K2039/5154 , A61K2039/6031 , A61K2039/70 , C12N2760/16134
摘要： A vaccine for immunization against Type A influenza virus is provided having an immunologically effective amount of peptide constructs obtained by linking together two or more peptides based on or derived from different molecules, and methods for producing the same. The peptide constructs have the formula P1-x-P2 or P2-x-P1 where P1 is associated with Type A influenza highly conserved protein such as but not limited to M2e matrix protein, NP1 nucleoprotein, HA2 core 1, and HA2 core 2, where P2 is a peptide construct causing a Th1 directed immune response by a set or subset of T cells to which the peptide P1 is attached or that binds to a dendritic cell or T cell receptor causing said set or subset of dendritic cell or T cells to which the peptide P1 is attached to initiate and complete, an immune response, and x is a direct bond or divalent linker for covalently bonding P1 and P2.
摘要翻译：提供了针对A型流感病毒免疫的疫苗，其具有免疫有效量的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获得的肽构建体及其制备方法。肽构建体具有式P1-x-P2或P2-x-P1，其中P1与A型流感高度保守的蛋白质相关，例如但不限于M2e基质蛋白，NP1核蛋白，HA2核心1和HA2核心2，其中P2是通过肽P1附着的T细胞的集合或亚群引起Th1定向免疫应答的肽结构，或者结合树突状细胞或T细胞受体，导致所述树突状细胞或T细胞的集合或子集肽P1连接起始和完成免疫应答，x是用于共价键合P1和P2的直接键或二价接头。

8. 发明申请

WO0136448A3 PREPARATION AND COMPOSITION OF PEPTIDES USEFUL FOR TREATMENT OF 审中-公开
标题翻译：用于治疗的肽的制备和组合
公开(公告)号：WO0136448A3
公开(公告)日：2002-02-07
申请号：PCT/US0041646
申请日：2000-10-27
申请人： CEL SCI CORP , ZIMMERMAN DANIEL H
发明人： ZIMMERMAN DANIEL H
IPC分类号： A61K38/00 , A61P11/06 , A61P37/02 , A61P37/08 , C07K14/00 , C07K14/78 , C07K19/00
CPC分类号： C07K14/78 , A61K38/00 , C07K14/4713
摘要： Peptide constructs including a first peptide segment which includes an amino acid sequence associated with autoimmune disease, asthma, allergy or xeno- or allograft transplantation rejections bonded directly or via a linker or spacer to a second peptide which binds to T cells and which will redirect the immune response from a harmful Th1 response to a less harmful Th2 response, or which will bind to T cells to initiate, but not complete, an immune response causing the T cells to which the first peptide binds, to undergo anergy and apoptosis, are useful in treating autoimmune conditions. For instance, the peptide construct NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK (SEQ ID NO:14) wherein Th2 stimulating Peptide G (SEQ ID NO:15) is covalently linked, via spacer GGG, to cardiac myosin molecule My1 (SEQ ID NO:16), can be used for treatment or prevention of myocarditis.
摘要翻译：包括第一肽段的肽构建体，其包括与自身免疫性疾病，哮喘，变态反应或异种或同种异体移植排斥相关的氨基酸序列，其直接或通过接头或间隔基结合至与T细胞结合的第二肽，并且将重定向有害的Th1应答对不太有害的Th2应答的免疫应答，或者与T细胞结合以引发但不完全的引起第一肽结合的T细胞的免疫应答进行无能和凋亡的免疫应答是有用的在治疗自身免疫性疾病。例如，可以使用其中Th2刺激肽G（SEQ ID NO：15）通过间隔基GGG共价连接到心肌肌球蛋白分子My1（SEQ ID NO：16）的肽构建体NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK（SEQ ID NO：14）用于治疗或预防心肌炎。

9. 发明申请

WO2009114869A3 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：WO2009114869A3
公开(公告)日：2010-09-23
申请号：PCT/US2009037312
申请日：2009-03-16
申请人： CEL SCI CORP , ZIMMERMAN DANIEL H
发明人： ZIMMERMAN DANIEL H
IPC分类号： A61K38/00 , A61K39/00
CPC分类号： C07K14/7055 , A61K38/00
摘要： Peptide constructs, which are useful in the treatment or prevention of autoimmune diseases, specifically rheumatoid arthritis (RA), wherein the peptide constructs have the formula PI-X-P2 where Pl is a peptide associated with autoimmune disease, allergy, asthma, host-versus-graft rejection, 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 Pl 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 Pl is attached to initiate, but not complete, an immune response causing the set or subset of T cells to undergo anergy and apoptosis; and x is a direct bond or linker for covalently bonding Pl and P2.
摘要翻译：肽构建体，其可用于治疗或预防自身免疫性疾病，特别是类风湿性关节炎（RA），其中肽构建体具有式PI-X-P2，其中P1是与自身免疫性疾病，过敏，哮喘，宿主 - 抗移植排斥，心肌炎，糖尿病和免疫介导的疾病，其结合T细胞的集合或亚群上的抗原受体; P2是将通过肽P1所连接的T细胞的集合或子集引起Th2定向的免疫应答的肽，或者将与T细胞受体结合，所述T细胞受体将引起所述肽的T细胞的集合或子集， P1附着以引发但不完全的导致T细胞的集合或子集进行无反应和凋亡的免疫应答; x是用于共价键合P1和P2的直接键或连接体。

10. 发明申请

WO2006015137A3 A METHOD FOR MANAGING CHOLESTEROL WITH A SERUM-FREE AND MITOGEN FREE CYTOKINE MIXTURE 审中-公开
标题翻译：一种用无血清和中浓度游离细胞因子混合物来管理胆固醇的方法
公开(公告)号：WO2006015137A3
公开(公告)日：2006-12-07
申请号：PCT/US2005026819
申请日：2005-07-29
申请人： CEL SCI CORP , KERSTEN GEERT , TALOR EYAL
发明人： KERSTEN GEERT , TALOR EYAL
IPC分类号： A61K45/00 , A61K38/21
CPC分类号： A61K38/191 , A61K38/193 , A61K38/2006 , A61K38/2013 , A61K38/217 , A61K2300/00
摘要： Methods for treting 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 comprises of specific ratios of cytokines IL-1ß, TNF-a, IFN-? and GM-CSF to Inteleukin 2 (IL-2) such as Leukocyte Inteleukin Injection (LI) or Multikine ®.
摘要翻译：治疗或预防疾病或病症的方法，例如心血管疾病，血脂异常; 血症; 高脂血症; 葡萄糖代谢紊乱; X综合征; 过氧化物酶体增殖物激活受体相关病症; 肥胖; 高血压; 和无血清且无丝裂原的混合物的肾脏疾病包含特定比例的细胞因子IL-1β，TNF-α，IFN- 和GM-CSF至白细胞介素2（IL-2）如白细胞白细胞介素注射液（LI）或Multikine®。

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