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1. 发明申请

US20060257420A1 Methods of preparation and composition of peptide constructs useful for treatment of autoimmune and transplant related host versus graft conditions 审中-公开
标题翻译：用于治疗自身免疫和移植相关宿主与移植物条件的肽构建体的制备方法和组合物
公开(公告)号：US20060257420A1
公开(公告)日：2006-11-16
申请号：US11443314
申请日：2006-05-31
申请人： Daniel Zimmerman
发明人： Daniel Zimmerman
IPC分类号： A61K39/00 , C07K14/47
CPC分类号： A61K39/00 , A61K2039/55516 , A61K2039/57 , C07K14/4713 , C07K19/00
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, asthma, allergies, and host versus graft (or graft versus host) rejection, as well as to 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, 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 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 anergy and apoptosis; and x is a direct bond or linker for covalently bonding P1 and P2.
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，哮喘，过敏和宿主与移植物（或移植物与宿主）排斥反应，以及含有其的组合物，生产方法和使用方法; 其中所述肽构建体具有式<βin-line-formula description =“In-line Formulas”end =“lead”？> P _{1 2 < in-line-formula description =“In-line Formulas”end =“tail”？>其中P <1>是与自身免疫性疾病，过敏，哮喘，宿主对移植物排斥反应，心肌炎相关的肽，糖尿病和免疫介导的疾病，其结合T细胞的集合或子集上的抗原受体; P 2是一种肽，其将导致T P细胞的集合或亚群的T H 2 H 2定向免疫应答，肽P < 附着或将结合T细胞受体，其将导致肽P 1附着的T细胞的集合或子集来引发但不完全的引起组或免疫反应的免疫应答 T细胞亚群进行无反应和凋亡; 和x是用于共价键合P 1和P 2的直接键或连接子。}

2. 发明授权

US06995237B1 Preparation and composition of peptides useful for treatment of autoimmune and transplant related graft versus host conditions 有权
标题翻译：用于治疗自身免疫和移植相关移植物与宿主条件的肽的制备和组合物
公开(公告)号：US06995237B1
公开(公告)日：2006-02-07
申请号：US10111645
申请日：2000-10-27
申请人： Daniel H. Zimmerman
发明人： Daniel H. Zimmerman
IPC分类号： A61K39/00 , C07K14/435
CPC分类号： C07K14/4713 , A61K39/0008 , A61K39/35 , A61K39/36 , C07K5/1008 , C07K14/435 , C07K2319/33 , C07K2319/40 , C07K2319/74
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键合至与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，或与T细胞结合以引发但不完全的引起第一个肽所结合的T细胞的免疫应答进行无反应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。

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

US20140286858A1 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：US20140286858A1
公开(公告)日：2014-09-25
申请号：US14122240
申请日：2012-05-24
申请人： CEL-SCI CORPORATION
发明人： Daniel H. Zimmerman , Eyal Talor , Kenneth Steven Rosenthal
IPC分类号： A61K47/48 , A61K51/02 , A61K39/00
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 constracts, 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 sued with dyes, radioisotopes, or therapeutic agents for detection of the immune target and/or treatment of cancer and autoimmune conditions.
摘要翻译：本发明涉及肽结构，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性疾病和含有其的组合物，方法制备其的方法及其使用方法：其中肽构建体具有式P1-x-P2，其中P2是与癌症形式或自身免疫病症相关的肽，P1是将结合一类免疫细胞的肽作为树突细胞。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，并且可以用染料，放射性同位素或治疗剂起诉用于检测免疫靶和/或治疗的癌症和自身免疫病症。

5. 发明申请

US20130266599A1 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反应的方法
公开(公告)号：US20130266599A1
公开(公告)日：2013-10-10
申请号：US13994092
申请日：2011-12-13
申请人： Daniel H. Zimmerman
发明人： Daniel H. Zimmerman
IPC分类号： A61K47/48 , A61K45/06
CPC分类号： A61K45/06 , A61K39/12 , A61K39/145 , 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型流感高度保守蛋白相关，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所连接的T细胞的集合或子集引起Th1定向的免疫应答的肽结构，或者结合树突细胞或T细胞受体，所述树突状细胞或T细胞受体导致树突状细胞或T细胞的集合或子集肽P1连接以引发和完成免疫应答，x是用于共价键合P1和P2的直接键或二价接头。

6. 发明授权

US6103239A Modified HGP-30 heteroconjugates, compositions and methods of use 失效
标题翻译：改性HGP-30杂合物，组合物和使用方法
公开(公告)号：US6103239A
公开(公告)日：2000-08-15
申请号：US695304
申请日：1996-08-09
申请人： Daniel H. Zimmerman , Prem S. Sarin
发明人： Daniel H. Zimmerman , Prem S. Sarin
IPC分类号： A61K38/00 , A61K39/00 , A61P31/18 , A61P37/04 , C07K14/16 , C07K14/74 , C07K16/00 , C07K16/10 , C07K19/00 , A61K39/21
CPC分类号： C07K14/005 , C07K14/70539 , C07K16/1054 , A61K39/00 , C12N2740/16222 , Y10S530/826
摘要： A heteroconjugate is formed by linking a T cell binding ligand (TCBL) such as Peptide J of .beta.-2 microglobulin to a modified HGP-30 antigentic peptide fragment of p17 gag peptide, such as. for exampleATL YSV HQR IDV KDTKEA LEK IEE EQN KS (SEQ ID NO: 5)The heteroconjugate is effective in eliciting a THI directed immune response and provides a vaccine composition for treating or preventing AIDS.
摘要翻译：通过将诸如β-2微球蛋白的肽J的T细胞结合配体（TCBL）与p17 gag肽的修饰的HGP-30抗原肽片段连接形成杂合物。例如ATL YSV HQR IDV KDT KEA LEK IEE EQN KS（SEQ ID NO：5）异源偶联物有效引发THI定向免疫应答，并提供用于治疗或预防AIDS的疫苗组合物。

7. 发明授权

US06093400A Modified HGP-30 peptides, conjugates, compositions and methods of use 失效
标题翻译：修饰的HGP-30肽，缀合物，组合物和使用方法
公开(公告)号：US06093400A
公开(公告)日：2000-07-25
申请号：US695301
申请日：1996-08-09
申请人： Daniel H. Zimmerman , Prem S. Sarin
发明人： Daniel H. Zimmerman , Prem S. Sarin
IPC分类号： A61K38/00 , A61K39/00 , A61P31/18 , C07K14/16 , A61K39/21
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , C12N2740/16222 , Y10S530/826 , Y10S530/861
摘要： An antigenic peptide fragment from the p17 gag protein of HIV includes a portion from HGP-30 and a contiguous portion from HGP-35 such that the peptide fragment is capable of inducing a TH1 immune response when administered to a person suffering from AIDS or at risk for AIDS. The peptide has from about 25 to about 37 amino acids, such as, for example, the sequence ##EQU1##
摘要翻译：来自HIV的p17 gag蛋白的抗原肽片段包括来自HGP-30的部分和来自HGP-35的连续部分，使得当向患有AIDS或患有风险的人施用时，该肽片段能够诱导TH1免疫应答为艾滋病。该肽具有约25至约37个氨基酸，例如该序列

8. 发明授权

US5652342A Heterofunctional cellular immunological reagents, vaccines containing same and methods for the use of same 失效
标题翻译：异种功能性细胞免疫试剂，含有相同的疫苗及其使用方法
公开(公告)号：US5652342A
公开(公告)日：1997-07-29
申请号：US354751
申请日：1994-12-08
申请人： Daniel H. Zimmerman , Donald A. Elliott
发明人： Daniel H. Zimmerman , Donald A. Elliott
IPC分类号： G01N33/53 , A61K38/00 , A61K39/00 , A61K39/395 , C07K1/20 , C07K1/22 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/03 , C07K14/075 , C07K14/09 , C07K14/16 , C07K14/18 , C07K14/315 , C07K14/42 , C07K14/445 , C07K14/47 , C07K14/52 , C07K14/54 , C07K14/545 , C07K14/55 , C07K14/725 , C07K14/74 , C07K14/80 , C07K16/00 , C07K19/00 , G01N33/569 , C07K14/705 , A61K39/385
CPC分类号： A61K39/092 , C07K14/005 , C07K14/315 , C07K14/42 , C07K14/445 , C07K14/47 , C07K14/70539 , C07K14/80 , G01N33/56972 , A61K2039/6031 , A61K38/00 , C07K2319/00 , C12N2710/10322 , C12N2710/16222 , C12N2740/16122 , C12N2770/24022 , C12N2770/32122 , Y10S530/868
摘要： The present invention relates to a heterofunctional cellular immunological reagent comprising at least two T cell specific binding ligands covalently linked together, wherein one of the T cell specific binding ligands binds to a specific class or subclass of T cells and another of the T cell specific binding ligands is an antigen associated with disease or a causative agent of disease, or epitope thereof. The present invention also relates to vaccines containing the heterofunctional cellular immunological reagents and methods for the use of the same.
摘要翻译：本发明涉及包含共价连接在一起的至少两个T细胞特异性结合配体的异功能细胞免疫试剂，其中T细胞特异性结合配体之一与T细胞的特定类别或亚类结合，另一种T细胞特异性结合配体是与疾病或疾病的致病因子或其表位相关的抗原。本发明还涉及含有异功能细胞免疫学试剂的疫苗及其使用方法。

9. 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.

10. 发明申请

US20110098444A1 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：US20110098444A1
公开(公告)日：2011-04-28
申请号：US12922687
申请日：2009-03-16
申请人： Daniel H. Zimmerman
发明人： Daniel H. Zimmerman
IPC分类号： C07K19/00 , C07K7/08
CPC分类号： C07K14/7055 , A61K38/00
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, 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 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 anergy and apoptosis; and x is a direct bond or linker for covalently bonding P1 and P2.
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，过敏，哮喘，宿主对移植物排斥，心肌炎，糖尿病和免疫介导的疾病相关的肽，其结合抗原受体 T细胞的集合或子集; 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连接以引发但不完全的导致T细胞的集合或亚群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。

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