公开(公告)号：WO2006015137A2

公开(公告)日：2006-02-09

申请号：PCT/US2005/026819

申请日：2005-07-29

Applicant: CEL-SCI CORPORATION ,  KERSTEN, Geert ,  TALOR, Eyal

Inventor： KERSTEN, Geert ,  TALOR, Eyal

IPC: A61K38/19

CPC classification number: A61K38/191 ,  A61K38/193 ,  A61K38/2006 ,  A61K38/2013 ,  A61K38/217 ,  A61K2300/00

Abstract: 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-1β, TNF-α, IFN-γ and GM-CSF to Inteleukin 2 (IL-2) such as Leukocyte Inteleukin Injection (LI) or Multikine ®.

Abstract translation: 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; 血症; 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; 和无血清和无丝分裂剂混合物的肾脏疾病包括细胞因子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。

公开(公告)号：WO2006004633A2

公开(公告)日：2006-01-12

申请号：PCT/US2005/022678

申请日：2005-06-28

Applicant: CEL-SCI CORPORATION ,  TALOR, Eyal

Inventor： TALOR, Eyal

IPC: A61K38/20

CPC classification number: A61K38/2006 ,  A61K38/191 ,  A61K38/193 ,  A61K38/2013 ,  A61K38/217 ,  A61K2300/00

Abstract: This invention relates to a breakthrough method for pre-sensitizing cancer prior to a therapeutic treatment such as chemotherapy, radiation therapy or immuno­therapy 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-C SF 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 immuno­therapy. One such novel cytokine mixture is Leukocyte Interleukin Injection (LI) or Multikineè, 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.

Abstract translation: 本发明涉及在治疗性治疗（例如化疗，放疗或免疫治疗）之前使癌前致敏的突破性方法，治疗和用于其方法中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-C SF与白细胞介素2（IL-2）组成的无血清和无丝裂原混合物， 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，放射疗法和免疫反应的易感性;治疗。 一种这样的新型细胞因子混合物是白细胞白细胞介素注射液（LI）或Multikine＆egrave，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。 p>

公开(公告)号：WO2005120550A2

公开(公告)日：2005-12-22

申请号：PCT/US2005/019263

申请日：2005-06-03

Applicant: CEL-SCI CORPORATION ,  TALOR, Eyal

Inventor： TALOR, Eyal

IPC: A61K38/20

CPC classification number: A61K38/193 ,  A61K31/5575 ,  A61K31/558 ,  A61K38/1808 ,  A61K38/191 ,  A61K38/195 ,  A61K38/20 ,  A61K38/2006 ,  A61K38/2013 ,  A61K38/217 ,  A61K45/06 ,  A61K2300/00

Abstract: 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-1β, TNF-α, IFN-γ 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.

Abstract translation: 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）为无血清和不含丝裂质素的混合物，每周5天，每周5天，每周5天的剂量为800IU /天，其特征在于细胞因子IL-1β，TNF-α ，IFN-γ和GM-CSF对白细胞介素2（IL-2）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。

公开(公告)号：WO2012162564A1

公开(公告)日：2012-11-29

申请号：PCT/US2012/039473

申请日：2012-05-24

Applicant: CEL-SCI CORPORATION ,  ZIMMERMAN, Daniel, H. ,  TALOR, Eyal ,  SUBBARAO, Kanta ,  BOONNAK, Kobporn

Inventor： ZIMMERMAN, Daniel, H. ,  TALOR, Eyal ,  SUBBARAO, Kanta ,  BOONNAK, Kobporn

IPC: A61K38/16 ,  A61K38/17 ,  A61K39/395 ,  A61P37/00

CPC classification number: A61K47/4833 ,  A61K39/0005 ,  A61K39/12 ,  A61K47/646 ,  A61K47/65 ,  A61K47/68 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/6031 ,  A61K2039/645 ,  C07K14/005 ,  C12N2760/16134 ,  Y02A50/401

Abstract: 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 P 1 -x-P 2 , where P 2 is a peptide associated with an infectious agent and P 1 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.

Abstract translation: 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的多肽，其可用于治疗或预防流感病毒和其它感染性疾病。 还公开了含有其的组合物，其制备方法及其使用方法，其中肽构建体具有式P1-x-P2，其中P2是与感染剂相关的肽，P1是肽 将结合一类免疫细胞，如树突状细胞。 肽结构可导致未成熟树突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感染因子的免疫应答。 与树突状细胞缀合的染料，放射性同位素或治疗剂可用于免疫靶的定位和/或疾病的预防或治疗性治疗。

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

Applicant: CEL SCI CORP ,  TALOR EYAL

Inventor： TALOR EYAL

IPC: A01N37/18 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K39/00

CPC classification number: A61K38/193 ,  A61K31/5575 ,  A61K31/558 ,  A61K38/1808 ,  A61K38/191 ,  A61K38/195 ,  A61K38/20 ,  A61K38/2006 ,  A61K38/2013 ,  A61K38/217 ,  A61K45/06 ,  A61K2300/00

Abstract: 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.

Abstract translation: 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。

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

Applicant: CEL SCI CORP ,  TALOR EYAL I

Inventor： TALOR EYAL I

IPC: 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 classification number: C07K19/00 ,  A61K38/00 ,  C07K14/70539

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2014176604A1

公开(公告)日：2014-10-30

申请号：PCT/US2014/035757

申请日：2014-04-28

Applicant: CEL-SCI CORPORATION ,  ZIMMERMAN, Daniel, H. ,  CARAMBULA, Roy ,  STEINER, Harold ,  TALOR, Eyal ,  GLANT, Tibor ,  MIKECZ, Katalin

Inventor： ZIMMERMAN, Daniel, H. ,  CARAMBULA, Roy ,  STEINER, Harold ,  TALOR, Eyal ,  GLANT, Tibor ,  MIKECZ, Katalin

IPC: C07K14/075 ,  A61K38/04 ,  A61P37/02

CPC classification number: A61K39/0008 ,  A61K35/28 ,  A61K38/00 ,  A61K47/64 ,  A61K2039/5154 ,  A61K2039/55516 ,  A61K2039/57 ,  C12N5/0636 ,  C12N5/0639

Abstract: 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 rheumatiod 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 PI is a peptide associated with autoimmune disease; P2 is a peptide which will cause a Th2 directed immune response; and X is a direct bond or linker for covalently bonding P1 and P2.

Abstract translation: 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，特别是风湿性关节炎（RA）和含有其的组合物， 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PI是与自身免疫疾病相关的肽; P2是会导致Th2定向免疫应答的肽; 并且X是用于共价键合P1和P2的直接键或接头。

公开(公告)号：WO2012162565A2

公开(公告)日：2012-11-29

申请号：PCT/US2012/039474

申请日：2012-05-24

Applicant: CEL-SCI CORPORATION ,  ZIMMERMAN, Daniel H. ,  TALOR, Eyal ,  ROSENTHAL, Kenneth

Inventor： ZIMMERMAN, Daniel H. ,  TALOR, Eyal ,  ROSENTHAL, Kenneth

IPC: A61K39/395 ,  A61K38/17 ,  A61K38/16 ,  A61P35/00

CPC classification number: A61K39/00 ,  A61K35/12 ,  A61K38/162 ,  A61K39/0008 ,  A61K39/0011 ,  A61K47/646 ,  A61K47/68 ,  A61K47/6901 ,  A61K51/02 ,  A61K2039/5154

Abstract: 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.

Abstract translation: 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。

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

Applicant: CEL SCI CORP ,  KERSTEN GEERT ,  TALOR EYAL

Inventor： KERSTEN GEERT ,  TALOR EYAL

IPC: A61K45/00 ,  A61K38/21

CPC classification number: A61K38/191 ,  A61K38/193 ,  A61K38/2006 ,  A61K38/2013 ,  A61K38/217 ,  A61K2300/00

Abstract: 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 ®.

Abstract translation: 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®。

公开(公告)号：WO2006004633A3

公开(公告)日：2006-03-16

申请号：PCT/US2005022678

申请日：2005-06-28

Applicant: CEL SCI CORP ,  TALOR EYAL

Inventor： TALOR EYAL

IPC: A61K38/00 ,  A61K20060101 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K45/00

CPC classification number: A61K38/2006 ,  A61K38/191 ,  A61K38/193 ,  A61K38/2013 ,  A61K38/217 ,  A61K2300/00

Abstract: This invention relates to a breakthrough method for pre-sensitizing cancer prior to a therapeutic treatment such as chemotherapy, radiation therapy or immuno­therapy 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-1ß, TNF-a, IFN-? and GM-C SF 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 immuno­therapy. One such novel cytokine mixture is Leukocyte Interleukin Injection (LI) or Multikineè, 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.

Abstract translation: 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。 细胞因子混合物是无血清和无丝分裂原混合物，其特征比例包括IL-1β，TNF-α，IFN- 和GM-C SF至白细胞介素2（IL-2），其有效诱导癌细胞进入增殖细胞周期，从而增加其对化学疗法，放射治疗和免疫治疗的易感性。 一种这样的新型细胞因子混合物是白细胞白介素注射（LI）或Multikineè，其可以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。