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1. 发明申请

WO2015088930A1 IMMUNOHISTOCHEMICAL PROXIMITY ASSAY FOR PD-1 POSITIVE CELLS AND PD-LIGAND POSITIVE CELLS IN TUMOR TISSUE 审中-公开
标题翻译：肿瘤组织中PD-1阳性细胞和PD-配体阳性细胞的免疫组织化学接近性测定
公开(公告)号：WO2015088930A1
公开(公告)日：2015-06-18
申请号：PCT/US2014/068980
申请日：2014-12-08
申请人： MERCK SHARP & DOHME CORP. , PIERCE, Robert, H. , YEARLEY, Jennifer, H. , TURNER, Scott, P. , DOGDAS, Belma , BAGCHI, Ansuman
发明人： PIERCE, Robert, H. , YEARLEY, Jennifer, H. , TURNER, Scott, P. , DOGDAS, Belma , BAGCHI, Ansuman
IPC分类号： A61P35/00
CPC分类号： G01N33/57492 , A61K2039/505 , C07K16/2818 , C07K2317/76 , C12Q1/6886 , C12Q2600/158 , G01N33/574 , G01N2333/70521 , G01N2333/70532 , G01N2800/52 , G06F19/00 , G06F19/34 , G06T7/0012 , G06T7/11 , G06T7/41 , G06T7/90 , G06T2207/10024 , G06T2207/10056 , G06T2207/10064 , G06T2207/20021 , G06T2207/30024 , G06T2207/30096 , G06T2207/30204
摘要： The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.
摘要翻译：本公开描述了用于在肿瘤组织中检测和定量表达PD-1的细胞（PD-1 +细胞）和PD-配体表达细胞（PD-L +细胞）的空间近邻对的IHC测定，以及使用测定以产生预测哪些癌症患者最有可能从PD-1拮抗剂治疗中获益的临近生物标志物。本公开还提供了用于测试邻近生物标志物的肿瘤样品的方法，以及基于测试结果用PD-1拮抗剂治疗受试者的方法。

2. 发明申请

WO2019241178A1 COMPLEX MOLECULE SUBSTRUCTURE IDENTIFICATION SYSTEMS, APPARATUSES AND METHODS 审中-公开
公开(公告)号：WO2019241178A1
公开(公告)日：2019-12-19
申请号：PCT/US2019/036449
申请日：2019-06-11
申请人： MERCK SHARP & DOHME CORP.
发明人： FRIDMAN, Arthur , BAGCHI, Ansuman , YU, Xiang , CANCILLA, Mark
IPC分类号： G16B50/00 , G16B45/00
摘要： Embodiments of the present invention provide a computer-implemented system and method for generating and searching a database containing all of the potential substructures (e.g., metabolites) of a chosen complex molecule based on minimum cleavable units (MCUs) of the chosen complex molecule, wherein each record in the generated database suitably defines the molecular weight and physical arrangement of each substructure. Embodiments of the invention also provide a user interface and a search engine for searching the database based on a query molecular weight (or query molecular weight range) to identify all of the substructures having a total molecular weight matching the query molecular weight or range. Embodiments of the invention are also capable of transmitting to a display device operated by an end user a description and/or a graphical representation of every identified substructure of the chosen complex molecule.

3. 发明申请

WO2019241191A1 CUT VERTEX METHOD FOR IDENTIFYING COMPLEX MOLECULE SUBSTRUCTURES 审中-公开
公开(公告)号：WO2019241191A1
公开(公告)日：2019-12-19
申请号：PCT/US2019/036467
申请日：2019-06-11
申请人： MERCK SHARP & DOHME CORP.
发明人： FRIDMAN, Arthur , BAGCHI, Ansuman , YU, Xiang , CANCILLA, Mark
IPC分类号： G16C20/20
摘要： Embodiments of the present invention avoid the processing problems associated with using conventional computer systems for identifying and characterizing all of the substructures (e.g., metabolites) of large complex molecules by using a defined minimum cleavable unit (MCU) and an MCU graph for a chosen molecule, as well as a "cut vertex" in the MCU graph for the chosen molecule. The system splits the MCU graph of the chosen molecule at the specified cut vertex to produce two separate MCU graph components (i.e., a first MCU subgraph and a second MCU subgraph) of the chosen molecule, and generates and traverses a first line graph component and a second line graph component, respectively, for the two MCU subgraph components with a graph traversing algorithm to generate and store in memory a first database of substructures and molecular weights for the first component, and a second database of substructures and molecular weights for the second line graph component. Subsequently, embodiments of the present invention can perform binary searches on the two databases (or the two subsections of a single database) to identify and produce graphic representations of all of the substructures of the chosen molecule that have molecular weights that match the query molecular weight (or range of query molecular weights), including the substructures of the chosen molecule that straddle (i.e., include) the cut vertex.

4. 发明申请

WO2009002418A2 T-CELL PEPTIDE EPITOPES FROM CARCINOEMBRYONIC ANTIGEN, IMMUNOGENIC ANALOGS, AND USES THEREOF 审中-公开
标题翻译：来自癌细胞抗原，免疫原性类似物的T细胞肽抗体及其用途
公开(公告)号：WO2009002418A2
公开(公告)日：2008-12-31
申请号：PCT/US2008/007551
申请日：2008-06-17
申请人： MERCK & CO., INC. , ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , AURISICCHIO, Luigi , SCARSELLI, Elisa , LA MONICA, Nicola , CILIBERTO, Gennaro , FRIDMAN, Arthur , PAK, Irene , BAGCHI, Ansuman
发明人： AURISICCHIO, Luigi , SCARSELLI, Elisa , LA MONICA, Nicola , CILIBERTO, Gennaro , FRIDMAN, Arthur , PAK, Irene , BAGCHI, Ansuman
IPC分类号： A61K39/00
CPC分类号： A61K39/0011
摘要： The present invention provides vaccines and pharmaceutical compositions which can, when administered to a patient, elicit an immune response to the carcinoembryonic antigen (CEA). Immunogenic peptide epitopes of human CEA are provided, as well as immunogenic peptide analogs which can induce an immune response cross-reactive against CEA which response is superior in quality to that induced by the corresponding wild-type epitope. Also disclosed herein are pharmaceutical compositions and vaccines comprising one or more of said peptides and analogs for prophylaxis and/or treatment of cancer. This invention further provides polynucleotides encoding at least one of the CEA analogs described herein, and vectors and host cells comprising said polynucleotides. Methods of inducing an immune response in a patient, in addition to methods of treatment using the immunogenic peptides, peptide analogs and polynucleotides disclosed herein are also disclosed.
摘要翻译：本发明提供疫苗和药物组合物，其可以在给予患者时引发对癌胚抗原（CEA）的免疫应答。提供了人CEA的免疫原性肽表位，以及可以诱导针对CEA交叉反应的免疫应答的免疫原性肽类似物，其反应性质优于相应的野生型表位诱导。本文还公开了包含用于预防和/或治疗癌症的一种或多种所述肽和类似物的药物组合物和疫苗。本发明还提供编码本文所述的至少一种CEA类似物的多核苷酸，以及包含所述多核苷酸的载体和宿主细胞。还公开了在患者体内诱导免疫应答的方法，除了使用本文公开的免疫原性肽，肽类似物和多核苷酸的治疗方法。

5. 发明申请

WO2006124408A3 SYSTEM AND METHOD FOR AUTOMATED SELECTION OF T-CELL EPITOPES 审中-公开
公开(公告)号：WO2006124408A3
公开(公告)日：2006-11-23
申请号：PCT/US2006/017897
申请日：2006-05-08
申请人： MERCK & CO., INC. , FRIDMAN, Arthur , BAGCHI, Ansuman , BAILEY, Wendy
发明人： FRIDMAN, Arthur , BAGCHI, Ansuman , BAILEY, Wendy
IPC分类号： G01N33/48 , G01N33/50 , C12Q1/70
摘要： Methodology for the automated selection and/or optimization of T-cell epitopes is disclosed. The invention provides a data processing system which utilizes sequence-based statistical pattern recognition to compute an epitope selection matrix based on the informational content of epitopes known to bind to a particular major histocompatibility class I allele. The resulting Bayes-corrected scoring matrix is used to predict the relative binding affinities of candidate T-cell epitopes derived from immunologically relevant antigens of self or foreign origin. One aspect of the invention describes an analytical method for identification of modifications in known or predicted T-cell epitopes, that confer upon the epitopes the ability to elicit stronger cellular immune response due to more efficient processing and/or presentation to T-cells. The disclosed epitope identification algorithm is applicable to the design of vaccines for infectious diseases, cancer and autoimmune diseases as well as for developing methods for the in vitro evaluation of cellular immunity.

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