公开(公告)号：US20140314812A1

公开(公告)日：2014-10-23

申请号：US14345988

申请日：2012-09-19

Applicant: St. Jude Children's Research Hospital

Inventor： Jason W. Rosch ,  Elaine I. Tuomanen ,  Jonathan A. McCullers

IPC: A61K39/09

CPC classification number: A61K39/092 ,  A61K2039/522 ,  A61K2039/543

Abstract: The present invention is an attenuated mutant strain of Streptococcus pneumonia that has a mutation in the FtsY gene. Vaccines, kits and methods for protecting a subject against Streptococcus pneumonia disease or colonization using the attenuated mutant strain are also provided.

Abstract translation: 本发明是在FtsY基因中具有突变的肺炎链球菌的减毒突变菌株。 还提供了使用减毒突变菌株来保护受试者免受肺炎链球菌疾病或定植的疫苗，试剂盒和方法。

公开(公告)号：US20140270453A1

公开(公告)日：2014-09-18

申请号：US14359722

申请日：2012-11-29

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

Inventor： Junyu Guo ,  Wilburn E. Reddick

IPC: G06T7/00 ,  G06T5/00

CPC classification number: G06T7/0012 ,  A61B5/055 ,  A61B5/7225 ,  A61B5/7271 ,  G01R33/4835 ,  G01R33/50 ,  G06T5/00 ,  G06T5/002 ,  G06T2207/10088 ,  G06T2207/20024

Abstract: Apparatus, methods, and other embodiments associated with the spectral analysis of T2 spectral data are described. One example magnetic resonance imaging (MRI) method includes accessing a data set comprising T2 spectral data associated with a magnetic resonance imaging (MRI) signal received from an object. The T2 spectral data is decomposed with multi-exponential functions to determine T2 spectra. The T2 spectral amplitude is regularized with a regularized constant. The regularized constant is sufficiently large to smooth the T2 spectra so adjacent pixels of the T2 spectral data have similar characteristics. The T2 spectral data is weighted so that the regularization is uniformly weighted for the spectral amplitudes. The T2 spectra is partitioned into intervals corresponding to myelin water fraction (MWF), tissue water fraction (TWF), Long T2 water fraction (LWF), and cerebrospinal fluid fraction (CSF). Parametric maps are generated based, at least in part, on the T2 spectral data.

Abstract translation: 描述了与T2光谱数据的光谱分析相关联的装置，方法和其它实施例。 一个例子磁共振成像（MRI）方法包括访问包括与从对象接收的磁共振成像（MRI）信号相关联的T2光谱数据的数据集。 T2光谱数据用多指数函数分解，以确定T2光谱。 T2频谱振幅用正则化常数正则化。 正则化常数足够大以平滑T2光谱，因此T2光谱数据的相邻像素具有相似的特性。 T2频谱数据被加权，使得正则化对于频谱幅度被均匀加权。 T2光谱分为对应于髓磷脂水分（MWF），组织水分（TWF），Long T2水分（LWF）和脑脊液分数（CSF）的间隔。 至少部分地基于T2光谱数据生成参数图。

公开(公告)号：US20130345091A1

公开(公告)日：2013-12-26

申请号：US14019186

申请日：2013-09-05

Applicant: St. Jude Children's Research Hospital

Inventor： James Downing ,  Charles Mullighan

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136

Abstract: Compositions and methods for the identification, prognosis, classification, treatment, and diagnosis of leukemia or a genetic predisposition to leukemia are provided. The present invention is based on the discovery of various genomic abnormalities of the IKZF1 gene which are shown herein to be associated with acute lymphoblastic leukemia (ALL), more particularly, associated with BCR-ABL1 positive ALL and/or shown to be associated with chronic myeloid leukemia (CML), more particularly, associated with blast crisis chronic myeloid leukemia (BC-CML) and/or the likelihood of progression into blastic transformation of CML. These various genomic abnormalities of the IKZF1 gene can further be used as prognostic markers to identify a subgroup of ALL having very poor outcomes. Such genomic abnormalities of IKZF1 find use in methods and compositions useful in the identification and/or prognosis and/or predisposition and/or treatment of ALL, more particularly, BCR-ABL1 positive ALL and/or in the identification and/or prognosis and/or predisposition and/or treatment of CML, more particularly, of BC-CML and/or the likelihood of progression into blastic transformation of CML and/or as prognostic markers to identify a subgroup of ALL having very poor outcomes.

Abstract translation: 提供了用于鉴定，预后，分类，治疗和诊断白血病或白血病遗传倾向的组合物和方法。 本发明基于IKZF1基因的各种基因组异常的发现，本文显示与急性淋巴细胞性白血病（ALL）相关，特别是与BCR-ABL1阳性ALL相关和/或显示与慢性淋巴细胞白血病 骨髓性白血病（CML），更特别是与爆发性危机慢性骨髓性白血病（BC-CML）相关和/或进展为CML变性的可能性。 IKZF1基因的这些各种基因组异常可进一步用作预后标记，以鉴定具有非常差的结果的ALL亚组。 IKZF1的这种基因组异常发现可用于鉴定和/或预后和/或倾向和/或治疗ALL，尤其是BCR-ABL1阳性ALL和/或鉴定和/或预后和/ 或倾向和/或治疗CML，更特别是BC-CML和/或进展为CML和/或作为预后标志物的急性转化的可能性以鉴定具有非常差的结果的ALL的亚组。

公开(公告)号：US20130266551A1

公开(公告)日：2013-10-10

申请号：US13826258

申请日：2013-03-14

Applicant: St. Jude Children's Research Hospital, Inc.

Inventor： DARIO CAMPANA ,  CHIHAYA IMAI

IPC: C07K16/28

CPC classification number: C07K16/2896 ,  A61K39/0011 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/2866 ,  C07K16/2878 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/30 ,  C12N5/0646 ,  C12N2501/2302 ,  C12N2501/2315 ,  C12N2501/599 ,  C12N2502/99 ,  C12N2510/00

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract translation: 本发明涉及能够表达原始和共刺激途径的嵌合受体，从而允许激活共刺激途径而不与天然配体结合。 受体的细胞质结构域含有4-1BB信号结构域的一部分。 本发明的实施方案涉及编码受体的多核苷酸，编码嵌合受体的载体和宿主细胞，特别包括T细胞和天然杀伤（NK）细胞及其使用方法。

公开(公告)号：US20030113343A1

公开(公告)日：2003-06-19

申请号：US10243977

申请日：2002-09-13

Applicant: St. Jude Children's Research Hospital

Inventor： Elaine I. Tuomanen ,  Khoosheh Gosink ,  Robert Masure

IPC: A61K039/02 ,  A61K048/00 ,  C12Q001/68 ,  G01N033/554 ,  G01N033/569 ,  C07H021/04 ,  C12P021/02 ,  C12N001/21 ,  C07K014/195

CPC classification number: G01N33/68 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  A61K2039/53 ,  C07K14/315 ,  C07K16/1275 ,  G01N33/56944 ,  G01N2333/315

Abstract: The present invention provides isolated polypeptides comprising an amino acid sequence of a choline binding protein CbpG. This invention provides an isolated polypeptide comprising an amino acid sequence of a choline binding polypeptide CbpG or N-terminal CbpG truncate, including analogs, variants, mutants, derivatives and fragments thereof. This invention further provides an isolated immunogenic polypeptide comprising an amino acid sequence of a choline binding protein CbpG. This invention provides an isolated nucleic acid encoding a polypeptide comprising an amino acid sequence of a choline binding protein CbpG. This invention provides pharmaceutical compositions, vaccines, and diagnostic and therapeutic methods of use of the isolated polypeptides and nucleic acids. Assays for compounds which alter or inactivate the polypeptides of the present invention for use in therapy are also provided.

Abstract translation: 本发明提供了包含胆碱结合蛋白CbpG的氨基酸序列的分离的多肽。 本发明提供了分离的多肽，其包含胆碱结合多肽CbpG或N-末端CbpG截短物的氨基酸序列，包括其类似物，变体，突变体，衍生物和片段。 本发明还提供了包含胆碱结合蛋白CbpG的氨基酸序列的分离的免疫原性多肽。 本发明提供编码包含胆碱结合蛋白CbpG的氨基酸序列的多肽的分离的核酸。 本发明提供药物组合物，疫苗以及使用分离的多肽和核酸的诊断和治疗方法。 还提供了用于改变或灭活本发明的多肽用于治疗的化合物的测定。

公开(公告)号：US20030022263A1

公开(公告)日：2003-01-30

申请号：US10024123

申请日：2001-12-17

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

Inventor： Michael Kastan ,  Christine Canman ,  Seong-Tae Kim ,  Dae-Sik Lim

IPC: C12Q001/48

CPC classification number: C12Q1/48 ,  G01N33/573 ,  G01N2333/9121

Abstract: The present invention relates to identification of the consensus sequence phosphorylated by ATM kinase. This, in turn, permitted identification of ATM kinase target proteins, and development of a convenient assay system for ATM kinase phosphorylation using fusion polypeptides as substrates. The assay system is adaptable to screening for ATM modulators, particularly inhibitors. In a specific embodiment, the substrate recognition sequence and mutagenized variants of this sequence were incorporated in a GST fusion protein and assayed for phosphorylation by ATM kinase. This assay system is useful in screening for ATM inhibitors. ATM function assays were validated using an ATM-kinase dead dominant-negative mutant.

公开(公告)号：US20020045192A1

公开(公告)日：2002-04-18

申请号：US09956425

申请日：2001-09-19

Applicant: St. Jude Children's Research Hospital

Inventor： Richard Kriwacki ,  Brian Bothner ,  William Lewis

IPC: G01N033/53 ,  A61K031/00 ,  G06F019/00 ,  G01N033/48 ,  G01N033/50

CPC classification number: C07K5/1019 ,  C07K14/4703 ,  G01N33/574 ,  G01N33/57496 ,  G01N2500/02 ,  G01N2500/04 ,  G16B15/00 ,  G16B20/00

Abstract: The present invention discloses that the binding of Arf with Dm2 results in specific domains of both proteins undergoing a dramatic transition from disordered conformations to extended structures comprised of null-strands. The presence of these specific domains is necessary and sufficient for the formation of the highly stable extended null structures formed between these two proteins. The present invention further exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific protein fragments derived from Arf and Dm2 that play a critical role in the binding of these two important regulatory proteins.

Abstract translation: 本发明公开了Arf与Dm2的结合导致两种蛋白质的特异性结构域经历从无序构象到由β-链构成的延伸结构的剧烈转变。 这些特定结构域的存在对于形成在这两种蛋白质之间形成的高度稳定的延伸的β结构是必需的和足够的。 本发明通过提供用于鉴定和/或设计模拟，抑制和/或增强Arf对Dm2的作用的化合物的方法进一步利用了这一发现。 本发明还提供了衍生自Arf和Dm2的特异性蛋白质片段，其在这两种重要的调节蛋白的结合中起关键作用。

公开(公告)号：US20250122166A1

公开(公告)日：2025-04-17

申请号：US18707401

申请日：2022-11-02

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Gisele A. NISHIGUCHI ,  Zoran RANKOVIC ,  Jeffery KLCO ,  Kevin MCGOWAN

IPC: C07D401/04 ,  A61K31/454 ,  A61P35/00

Abstract: In one aspect, the disclosure relates to substituted N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)benzamide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US12264335B2

公开(公告)日：2025-04-01

申请号：US18067199

申请日：2022-12-16

Applicant: National University of Singapore ,  St. Jude Children's Research Hospital, Inc.

Inventor： Dario Campana ,  David Shook ,  Masaru Imamura

IPC: C07K14/54 ,  A61K38/20 ,  A61K39/00 ,  C07K14/705 ,  C12N5/00 ,  C12N5/0783 ,  C12N5/16 ,  C12N15/62

Abstract: The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

公开(公告)号：US12257319B2

公开(公告)日：2025-03-25

申请号：US16897900

申请日：2020-06-10

Applicant: UCL BUSINESS LTD ,  THROMBOSIS RESEARCH INSTITUTE ,  ST. JUDE CHILDREN'S RESEARCH HOSPITAL

Inventor： Amit Nathwani ,  Natalie Ward ,  Adrian Thrasher ,  Edward Tuddenham ,  John McVey ,  John Gray ,  Andrew Davidoff

IPC: C07H21/04 ,  A61K31/70 ,  A61K38/37 ,  A61K48/00 ,  C07K14/755 ,  C12N7/00 ,  C12N15/63 ,  C12N15/86 ,  A01K67/00 ,  A61K38/00

Abstract: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocyte biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.