公开(公告)号：US20160304858A1

公开(公告)日：2016-10-20

申请号：US15101248

申请日：2014-12-02

Applicant: BRANDEIS UNIVERSITY ,  THE GENERAL HOSPITAL CORPORATION

Inventor： Isaac J. KRAUSS ,  Satoru HORIYA ,  Yollete V. GUILLEN SCHLIPPE

IPC: C12N15/10 ,  G01N33/68

Abstract: The invention relates to a method for selecting a glycopolypeptide that binds to a target protein, the method including the steps of providing a pool of glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex; combining the pool with a target protein to form a mixture; incubating the mixture for a period of time sufficient to allow any target protein to bind to one or more of the glycopolypeptides, thereby forming glycopolypeptide-target protein complexes; and isolating from the mixture the glycopolypeptide-target protein complexes, thereby identifying a plurality of selected glycopolypeptides.

Abstract translation: 本发明涉及一种选择与靶蛋白结合的糖多肽的方法，所述方法包括以下步骤：通过嘌呤霉素接头融合至编码mRNA-cDNA双链体的糖多肽池; 将池与目标蛋白结合形成混合物; 将混合物温育足以允许任何靶蛋白结合一种或多种糖多肽的时间，从而形成糖多肽 - 靶蛋白复合物; 并从混合物中分离出糖多肽 - 靶蛋白复合物，从而鉴定出多个选定的糖多肽。

公开(公告)号：US20190117748A1

公开(公告)日：2019-04-25

申请号：US16092137

申请日：2017-04-06

Applicant: BRANDEIS UNIVERSITY

Inventor： Isaac J. KRAUSS ,  Joel Sebastian TEMME

IPC: A61K39/00 ,  C12N15/117 ,  C07H15/22 ,  A61K39/39 ,  C12N15/115 ,  A61P31/18

CPC classification number: A61K39/0005 ,  A61K39/39 ,  A61K2039/51 ,  A61K2039/545 ,  A61P31/18 ,  C07H15/22 ,  C07H21/04 ,  C12N15/10 ,  C12N15/115 ,  C12N15/117 ,  C12N2310/13 ,  C12N2310/16 ,  C12N2310/351 ,  C12N2320/30

Abstract: Disclosed are oligonucleotides that binds specifically to HIV neutralizing monoclonal antibody 2G12 with a K4 value lower than 20 nM, the oligonucleotide comprising a predicted structure, at 37° C., having exactly one stem-loop whereby the loop comprises the nucleotide sequence of AACCNACGGANAAA (SEQ ID NO: 1), where N is a modified nucleoside base, and the stem includes at least 3 nucleotide base-pairs and one of the nucleotides in the stem includes a modified nucleoside base, wherein the modified nucleoside base has the structure -B-L-A where A is a branched-chain Man9 oligosaccharide, L is a linker molecule, and B is independently a pyrimidine or pyridine base linked to the sugar-phosphate backbone of the oligonucleotide. Immunogenic conjugates that include the oligonucleotide, and pharmaceutical compositions that include the oligonucleotide or the immunogenic conjugate are also disclosed. Various method of using the oligonucleotides, immunogenic conjugates, and pharmaceutical compositions are also disclosed.

公开(公告)号：US20160304874A1

公开(公告)日：2016-10-20

申请号：US15101292

申请日：2014-12-02

Applicant: BRANDEIS UNIVERSITY

Inventor： Isaac J. KRAUSS

IPC: C12N15/117 ,  A61K39/21 ,  C12P19/34 ,  G01N33/53 ,  G01N33/68 ,  C12N15/10

CPC classification number: C12N15/117 ,  A61K39/21 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/572 ,  A61K2039/585 ,  C12N15/1058 ,  C12N2310/16 ,  C12N2310/17 ,  C12N2310/351 ,  C12N2310/531 ,  C12N2320/30 ,  C12P19/34 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5308 ,  G01N33/57415 ,  G01N33/57419 ,  G01N33/57423 ,  G01N33/57434 ,  G01N33/6854 ,  G01N2333/162 ,  G01N2333/9121 ,  Y02A50/57

Abstract: The invention relates to an oligonucleotide including one or more modified nucleoside bases having the structure -B-L-A wherein for each of the modified nucleosides A is independently a monosaccharide or oligosaccharide, L is a linker molecule, and B is independently a pyrimidine or pyridine base linked to the sugar-phosphate backbone of the oligonucleotide; and wherein the oligonucleotide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM. Immunogenic conjugates that include the oligonucleotide, and pharmaceutical compositions that include the oligonucleotide or the immunogenic conjugate are also disclosed. Various method of using the oligonucleotides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral or bacterial infection, treating a cancerous condition, and detecting a neutralizing antibody. A method is also disclosed for selecting the oligonucleotides using an alternative Selection of Modified Aptamers (SELMA).

Abstract translation: 本发明涉及包含一个或多个具有结构-BLA的修饰的核苷碱基的寡核苷酸，其中对于每个修饰的核苷A，A独立地是单糖或寡糖，L是连接分子，B独立地是与 寡核苷酸的糖 - 磷酸骨架; 并且其中寡核苷酸以小于100nM的亲和力特异性结合与碳水化合物结合的单克隆抗体。 还公开了包含寡核苷酸的免疫原性缀合物和包含寡核苷酸或免疫原性缀合物的药物组合物。 公开了使用寡核苷酸，免疫原性缀合物和药物组合物的各种方法，包括诱导免疫应答，抑制病毒或细菌感染，治疗癌症和检测中和抗体。 还公开了使用修饰的选择性选择（SELMA）来选择寡核苷酸的方法。

公开(公告)号：US20160304628A1

公开(公告)日：2016-10-20

申请号：US15101221

申请日：2014-12-02

Applicant: BRANDEIS UNIVERSITY

Inventor： Isaac J. KRAUSS ,  Satoru HORIYA

IPC: C07K19/00 ,  C07K16/10 ,  G01N33/68 ,  A61K39/21

Abstract: The invention relates to a glycopolypeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopolypeptide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopolypeptide, and pharmaceutical compositions that include the glycopolypeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopolypeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral or bacterial infection, treating a cancerous condition, and detecting a neutralizing antibody.

Abstract translation: 本发明涉及包含一个或多个具有包含单糖或寡糖的侧链的修饰的氨基酸残基的糖多肽，其中所述糖多肽特异性结合小于100nM亲和力的碳水化合物结合单克隆抗体。 还公开了包含糖多肽的免疫原性缀合物和包括糖多肽或免疫原性缀合物的药物组合物。 公开了使用糖多肽，免疫原性缀合物和药物组合物的各种方法，包括诱导免疫应答，抑制病毒或细菌感染，治疗癌症和检测中和抗体。

公开(公告)号：US20160051690A1

公开(公告)日：2016-02-25

申请号：US14744985

申请日：2015-06-19

Applicant: Brandeis University

Inventor： Isaac J. KRAUSS ,  Lizbeth K. HEDSTROM ,  Iain S. MACPHERSON

IPC: A61K47/48 ,  C12N7/00 ,  A61K39/21

CPC classification number: C07H21/04 ,  A61K39/21 ,  A61K47/549 ,  A61K47/646 ,  A61K2039/55505 ,  A61K2039/55511 ,  A61K2039/6068 ,  A61K2039/6081 ,  A61K2039/627 ,  C07H15/22 ,  C12N7/00 ,  C12N15/1048 ,  C12N15/1058

Abstract: Described herein are oligosaccharide-oligonucleotide conjugates useful as vaccines against one or more human or veterinary therapeutic indications, and methods of synthesizing and identifying them. The conjugates may be identified using non-human antibodies as binding targets, thereby expanding the power and scope of the invention. Efficacious conjugates may be identified through an iterative screening process.

Abstract translation: 本文描述了可用作针对一种或多种人或兽医治疗适应症的疫苗的寡糖 - 寡核苷酸缀合物，以及合成和鉴定它们的方法。 可以使用非人抗体作为结合靶标鉴定缀合物，从而扩大本发明的功能和范围。 有效的缀合物可以通过迭代筛选过程来鉴定。

公开(公告)号：US20220090055A1

公开(公告)日：2022-03-24

申请号：US17288414

申请日：2019-10-24

Applicant: BRANDEIS UNIVERSITY

Inventor： Isaac J. KRAUSS ,  Satoru HORIYA ,  Jennifer BAILEY

IPC: C12N15/10 ,  C07K19/00

Abstract: The invention relates to a glycopeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopeptide binds specifically to a carbohydrate-binding monoclonal antibody from PGT128 family, preferably with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopeptide, and pharmaceutical compositions that include the glycopeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral infection, treating a cancerous condition, and detecting a neutralizing antibody.

公开(公告)号：US20200002699A1

公开(公告)日：2020-01-02

申请号：US16486248

申请日：2018-02-19

Applicant: BRANDEIS UNIVERSITY

Inventor： Ian S. MACPHERSON ,  Isaac J. KRAUSS

IPC: C12N15/10 ,  C12N9/12 ,  C12Q1/6811

Abstract: The present invention is directed to the method for selecting an RNA molecule that binds to a target molecule and a kit for carrying out the method. This method includes: providing a pool of oligonucleotide complexes that each comprise a ds-DNA molecule and an RNA molecule, the ds-DNA molecule comprising a first DNA strand at least partially annealed to a first region of the RNA molecule, whereby a second region of the RNA molecule is free to adopt a secondary structure; exposing the pool to a target molecule and allowing the second region of the RNA to bind the target molecule; and selecting from the pool one or more oligonucleotide complexes comprising an RNA molecule having the second region bound to the target molecule.