公开(公告)号：US09511092B2

公开(公告)日：2016-12-06

申请号：US14764070

申请日：2014-01-28

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC. ,  NATIONAL UNIVERSITY OF SINGAPORE

Inventor： Dario Campana ,  Yu-Hsiang Chang

IPC: A01N63/00 ,  A61K35/17 ,  A61K38/00 ,  C12N5/0783 ,  C07K14/725 ,  C07K14/705

CPC classification number: C12N5/0646 ,  A61K35/17 ,  A61K38/00 ,  C07K14/705 ,  C07K14/7051 ,  C07K14/7056 ,  C07K2319/00 ,  C07K2319/70 ,  C12N5/0087 ,  C12N2510/00

Abstract: The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for the use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.

Abstract translation: 本发明提供了包含NKG2D，DAP10和CD3ζ的嵌合受体。 还公开了包含该嵌合受体的组合物和用于制备和使用其以增强NK细胞的细胞毒性和抗肿瘤能力的方法。 本发明还包括在用于治疗癌症和其它增殖性疾病以及感染性疾病的方法中使用NKG2D-DAP10-CD3ζ多肽，载体和细胞的方法。

公开(公告)号：US20160074675A1

公开(公告)日：2016-03-17

申请号：US14888363

申请日：2014-04-30

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION ,  PURDUE RESEARCH FOUNDATION ,  St. Jude Children's Research Hospital, Inc.

Inventor： Vadim Moskvin ,  Keith Michael Stantz

IPC: A61N5/10 ,  A61B8/08

CPC classification number: A61N5/1071 ,  A61B8/08 ,  A61B8/0833 ,  A61B8/483 ,  A61B2019/524 ,  A61N5/1031 ,  A61N5/1039 ,  A61N5/1075 ,  A61N2005/1034 ,  A61N2005/1076 ,  A61N2005/1087

Abstract: A method of verifying therapeutic proton beam delivery accuracy by ultrasound tomographic imaging to map three dimensional (3D) proton dose through the detection of ionizing radiation induced thermo-acoustic signal from the proton beam.

Abstract translation: 一种通过超声层析成像来验证治疗质子束传递精度的方法，通过检测离子辐射引起的来自质子束的热声信号来映射三维（3D）质子剂量。

公开(公告)号：US20160009784A1

公开(公告)日：2016-01-14

申请号：US14872947

申请日：2015-10-01

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

Inventor： Dario Campana ,  Chihaya Imai

IPC: C07K14/705 ,  C07K14/725

CPC classification number: C07K14/70578 ,  A61K39/395 ,  C07K14/47 ,  C07K14/7051 ,  C07K14/70517 ,  C07K16/2866 ,  C07K16/2878 ,  C07K16/2896 ,  C07K2319/32 ,  C12N5/0646 ,  C12N2501/23 ,  C12N2502/11 ,  C12N2502/99

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：US20150266959A1

公开(公告)日：2015-09-24

申请号：US14434129

申请日：2013-10-08

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

Inventor： Dario A. A. Vignali ,  Seng-ryong Woo ,  Greg M. Delgoffe

IPC: C07K16/28

CPC classification number: C07K16/2863 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K31/713 ,  A61K38/1709 ,  A61K39/0011 ,  A61K39/39541 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/5158 ,  C07K16/2803 ,  C07K2317/32 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/32 ,  C12N5/0637 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2501/165

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and/or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.

Abstract translation: 本发明涉及通过经由Neuropilin-1：信号素轴影响调节性T细胞稳定性和功能来治疗癌症，感染和各种炎症和自身免疫病症。 本发明通过证明调节性T细胞（Treg） - 限制性神经蛋白-1（Nrp 1）与细胞表面配体信号素-4a（Sema4a）（例如，常规T细胞（Tconv））相互作用来满足这一点和其他需要， 常规树突状细胞（cDC）和/或浆细胞样树突状细胞（pDC））以增强寄生虫功能并增强其在炎症部位的存活。

公开(公告)号：US20030224422A1

公开(公告)日：2003-12-04

申请号：US10407790

申请日：2003-04-04

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

Inventor： William Edward Evans ,  Mary V. Relling

IPC: C12Q001/68

CPC classification number: C12Q1/6886 ,  C12Q1/6809 ,  C12Q2600/106 ,  C12Q2600/158 ,  C12Q2565/501

Abstract: A general method for identifying biological targets for improving currently available therapies is provided. Target genes and their expression products are identified based on their response to therapy as determined through pre- and post-therapy expression profiles. In another aspect, differences in expression profiles between responsive and nonresponsive patients are taken into account to identify potential new targets for the development of novel medications or treatments. The invention also provides methods for comparing therapies to predict which will have the best therapeutic efficacy and/or the least potential deleterious. The methods taught are specifically applied to identify targets for improving treatment of acute lymphoblastic leukemia.

Abstract translation: 提供了用于鉴定改善目前可用疗法的生物靶标的一般方法。 目标基因及其表达产物是根据通过治疗前和治疗后表达谱确定的对治疗的反应来鉴定的。 另一方面，考虑到反应性和非反应性患者之间的表达谱的差异，以确定用于开发新药物或治疗的潜在新目标。 本发明还提供了用于比较治疗以预测哪些具有最佳治疗功效和/或最不利潜在的方法。 所教导的方法专门用于鉴定改善急性淋巴细胞白血病治疗的靶点。

公开(公告)号：US20030082173A1

公开(公告)日：2003-05-01

申请号：US10293816

申请日：2002-11-12

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

Inventor： Richard J. Bram ,  Gotz Von Bulow

IPC: G01N033/567 ,  A61K039/395

CPC classification number: C07K16/2878 ,  A01K2217/075 ,  A61K38/00 ,  C07K14/70578 ,  C07K2317/75 ,  Y02A50/411 ,  Y10S530/82

Abstract: A novel lymphocyte receptor protein, its DNA sequence, and its role in the calcium activation pathway is described. The protein, or genetically engineered constructs encoding it, are shown to increase lymphocyte response, and to identify ligands of the protein receptor. Antibodies to the proteins of the invention are generated for diagnostic therapeutics. The protein and DNA can also be used for diagnostic purposes and for identifying agents for modulating the calcium induced activation pathway. A particular advantage of the present invention is that it provides lymphocyte activation of receptor found on all B cells, but only on a subset of T cells. The receptor can thus be targeted to specifically regulate B cell responses without affecting mature T cell activity. Such targeting specificity is always advantageous, particularly where an increase or decrease of antibody production is desired, e.g., during an infection (increase) or to avoid immune complex deposition complications (rheumatoid arthritis, glomerulonephritis, and other auto immune conditions).

Abstract translation: 描述了一种新型淋巴细胞受体蛋白，其DNA序列及其在钙激活途径中的作用。 显示蛋白质或编码它的遗传工程化构建体可增加淋巴细胞反应，并鉴定蛋白质受体的配体。 生成本发明蛋白质的抗体用于诊断治疗。 蛋白质和DNA也可用于诊断目的，并用于鉴定用于调节钙诱导的激活途径的药剂。 本发明的一个特别优点在于它提供了在所有B细胞上发现的受体的淋巴细胞活化，但是仅提供在T细胞的一个子集上。 因此受体可以被靶向以特异性调节B细胞应答而不影响成熟的T细胞活性。 这种靶向特异性总是有利的，特别是在需要增加或减少抗体产生的情况下，例如在感染（增加）期间或避免免疫复合物沉积并发症（类风湿性关节炎，肾小球性肾炎和其他自身免疫病症）时。

公开(公告)号：US20250090526A1

公开(公告)日：2025-03-20

申请号：US18642382

申请日：2024-04-22

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

Inventor： Suzanne JACKOWSKI ,  Charles O. ROCK ,  Richard E. LEE ,  Lalit Kumar SHARMA ,  Mi Kyung YUN ,  Chitra SUBRAMANIAN ,  Rajendra P. TANGALLAPALLY ,  Anne V. EDWARDS ,  Robert ZAMBONI ,  T. Jagadeeswar REDDY ,  Jiuyu LIU

IPC: A61K31/501 ,  A61K31/197 ,  A61K31/205 ,  A61P3/00

Abstract: The present disclosure relates to methods of treating a coenzyme A reduction, elevation, sequestration, toxicity, or redistribution (CASTOR) disease such as, for example, defects in fatty acid oxidation enzymes, methylmalonic acidemia, glutaric acidemia, propionic academia, and HMG-CoA lyase, via small molecule modulators of CoA levels. 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 invention.

公开(公告)号：US12053490B2

公开(公告)日：2024-08-06

申请号：US16759263

申请日：2018-10-25

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

Inventor： Terrence L. Geiger ,  Wenting Zheng ,  Carol E. O'Hear

IPC: A61K35/17 ,  C07K14/705 ,  C07K14/725 ,  C07K16/28 ,  C12N15/00 ,  C12N15/62

CPC classification number: A61K35/17 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70578 ,  C07K16/2896 ,  C12N15/00 ,  C12N15/62 ,  C07K16/2803 ,  C07K2317/622 ,  C07K2319/03

Abstract: The application relates to a chimeric receptor that targets CD33 and allows activation of the co-stimulatory pathway without binding the natural ligand. The application also relates to polynucleotides that encode the chimeric receptor, vectors, and host cells comprising the chimeric receptor. The application also relates to methods for preparing host cells comprising a chimeric antigen receptor in order to improve the in vivo persistence of the chimeric antigen receptor host cells.

公开(公告)号：US20240139315A1

公开(公告)日：2024-05-02

申请号：US18541691

申请日：2023-12-15

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

Inventor： Jian ZUO ,  Fei ZHENG ,  Tetsuji YAMASHITA ,  Zoe KELLARD ,  Tal TEITZ ,  Jaeki MIN ,  Taosheng CHEN

IPC: A61K39/395 ,  A61K31/18 ,  A61K31/422 ,  A61K31/44 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/58 ,  A61K31/713 ,  A61K38/17 ,  A61K45/06 ,  A61P27/16

CPC classification number: A61K39/3955 ,  A61K31/18 ,  A61K31/422 ,  A61K31/44 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/58 ,  A61K31/713 ,  A61K38/1709 ,  A61K45/06 ,  A61P27/16

Abstract: Methods and compositions using an inhibitor of EGFR signaling for prevention or an inhibitor of EGFR signaling and a nucleic acid molecule encoding an atonal-associated factor for treatment of hearing loss are described.

公开(公告)号：US20240132463A1

公开(公告)日：2024-04-25

申请号：US18368497

申请日：2023-09-14

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

Inventor： Marcus FISHER ,  Fatemeh KERAMATNIA ,  Kevin MCGOWAN ,  Jaeki MIN ,  Gisele A. NISHIGUCHI ,  Jeanine PRICE ,  Zoran RANKOVIC ,  Sourav Das ,  Charles G. MULLIGHAN ,  Yunchao CHANG

IPC: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  A61P35/00 ,  A61P35/02 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

CPC classification number: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  A61P35/00 ,  A61P35/02 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide 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 and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. 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.