公开(公告)号：US20060216303A1

公开(公告)日：2006-09-28

申请号：US10874990

申请日：2004-06-23

申请人： Fernando do Couto ,  Roberto Ceriani ,  Jerry Peterson ,  Eduardo Padlan

发明人： Fernando do Couto ,  Roberto Ceriani ,  Jerry Peterson ,  Eduardo Padlan

IPC分类号： G01N33/574 ,  A61K39/00 ,  C07K16/30 ,  C07K14/82

CPC分类号： C07K16/465 ,  A61K38/00 ,  A61K51/1027 ,  A61K51/1051 ,  C07K16/28 ,  C07K16/3015 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/567 ,  C07K2317/92 ,  G01N33/574

摘要： An analogue peptide that comprises the variable regions of the light or heavy chains of an antibody of a first species selectively binding to a carcinoma antigen has 1 to 46 amino acids of the framework regions per chain substituted with amino acids such as those present in equivalent positions in antibodies of a species other than the first species, or fragments thereof comprising 1 to 3 variable region CDRs per chain and optionally flanking regions thereof of 1 to 10 or more amino acids, alone or with an N-terminal fragment of 1 to 10 or more amino acids, combinations or mixtures thereof. The polypeptide may also comprise an effector agent and/or be glycosylated, and is presented as a composition with a carrier. The analogue peptides are used in diagnostic kits for carcinomas and methods for in vivo imaging and treating a primary or metastasized carcinoma, and in vitro diagnosing a carcinoma, ex vivo purging neoplastic cells from a biological fluid. RNAs and DNAs encode the analogue peptide, and a hybrid vector carrying the nucleotides and transfected cells express the peptides and a method produces the analogue peptide. An anti-idiotype polypeptide comprises polyclonal antibodies raised against an anti-carcinoma antibody or the analogue peptide of this invention, monoclonal antibodies thereof, Fab, Fab′, (Fab′)2, CDR, variable region, or analogues or fragments thereof, combinations thereof with an oligopeptide comprising a TRP trimer, tandem repeats thereof, or combination or mixtures thereof. An anti-idiotype hybrid polypeptide with an effector agent and the anti-idiotype polypeptide, an anti-carcinoma vaccine, an anti-carcinoma vaccination kit, a method of vaccinating against carcinoma and a method of lowering the serum concentration of a circulating antibody or polypeptide are provided.

摘要翻译： 包含选择性结合癌抗原的第一种物种的抗体的轻链或重链的可变区的类似肽具有每个被每个氨基酸取代的骨架区的1至46个氨基酸，例如存在于等同位置 在除第一种之外的物种的抗体中，或其片段包含1至3个可变区CDR，每个链及其任选侧翼区为1至10个或更多个氨基酸，单独或与1-10个N末端片段或 更多的氨基酸，其组合或混合物。 多肽还可以包含效应剂和/或被糖基化，并且作为具有载体的组合物呈递。 类似物肽用于癌症的诊断试剂盒和体内成像和治疗原发性或转移性癌症的方法，以及体外诊断癌症，从生物流体中离体清除肿瘤细胞。 RNA和DNA编码类似物肽，携带核苷酸和转染细胞的杂交载体表达肽，一种方法产生类似肽。 抗独特型多肽包括针对本发明的抗癌抗体或类似物肽产生的多克隆抗体，其单克隆抗体，Fab，Fab'，（Fab'）2，CDR，可变区， 或其类似物或片段，其与包含TRP三聚体，其串联重复序列或其组合或混合物的寡肽的组合。 具有效应剂和抗独特型多肽的抗独特型杂合多肽，抗癌疫苗，抗癌疫苗试剂盒，疫苗接种癌的方法和降低循环抗体或多肽的血清浓度的方法 被提供。

公开(公告)号：US20050169915A1

公开(公告)日：2005-08-04

申请号：US10965616

申请日：2004-10-13

申请人： Fernando Do Couto ,  Roberto Ceriani ,  Jerry Peterson

发明人： Fernando Do Couto ,  Roberto Ceriani ,  Jerry Peterson

IPC分类号： A61K38/00 ,  A61K51/10 ,  C07K16/30 ,  A61K39/395 ,  C07K16/44

CPC分类号： A61K51/1051 ,  A61K38/00 ,  A61K51/1081 ,  A61K51/1093 ,  A61K51/1096 ,  A61K2039/505 ,  A61K2121/00 ,  A61K2123/00 ,  C07K16/3015 ,  C07K2317/24 ,  C07K2317/56

摘要： The present invention provides recombinant peptides that specifically and selectively bind to the human milk fat globule (HMFG) antigen, BA46. In particular, the present invention provides recombinant variants of the Mc3 antibody, including humanized versions of Mc3. The variant Mc3 peptides are particularly useful for diagnostic, prognostic, and therapeutic applications in the field of breast cancer. The present invention also provides methods for the humanization of antibodies such as murine monoclonal antibodies. The novel humanization methods are applied to the production of humanized Mc3 antibodies and it is shown that these humanized antibodies retain the ability to engage in high affinity binding to their cognate antigen. Such humanization enables the use of these antibodies for immunodiagnostic and immunotherapeutic applications in humans.

摘要翻译： 本发明提供了特异性且选择性地结合人乳脂肪球（HMFG）抗原BA46的重组肽。 特别地，本发明提供Mc3抗体的重组变体，包括人源化形式的Mc3。 该变体Mc3肽特别可用于乳腺癌领域的诊断，预后和治疗应用。 本发明还提供了抗体如人单克隆抗体人源化的方法。 新型人源化方法适用于人源化Mc3抗体的产生，并且显示这些人源化抗体保留参与与其同源抗原的高亲和力结合的能力。 这样的人源化使得能够使用这些抗体用于人体免疫诊断和免疫治疗应用。