公开(公告)号：US20230049954A1

公开(公告)日：2023-02-16

申请号：US17640281

申请日：2020-09-04

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Cristina PUIG-SAUS ,  Antoni RIBAS ,  Yvonne CHEN

IPC: A61K35/17 ,  C07K14/705 ,  C07K14/725 ,  A61P35/00 ,  C07K16/28 ,  A61P17/00

Abstract: Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

公开(公告)号：US20210353678A1

公开(公告)日：2021-11-18

申请号：US17390673

申请日：2021-07-30

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Theodore Lee ROTH ,  Eric SHIFRUT ,  Alexander Marson ,  Cristina PUIG SAUS ,  Antoni RIBAS

IPC: A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20210386780A1

公开(公告)日：2021-12-16

申请号：US17281551

申请日：2019-09-30

Applicant: The Regents of the University of California ,  HIGHLIGHT THERAPEUTICS S.L.

Inventor： Anusha KALBASI ,  Antoni RIBAS ,  Marisol QUINTERO

IPC: A61K35/17 ,  A61K31/713 ,  A61K47/59 ,  A61P35/00

Abstract: Disclosed herein are improved methods of treating cancer in a subject by administering Adoptive Cell Therapy, in particular in those subjects affected by a cancer that presents a loss of function, mutation, or other disruption in an immune pathway. The loss of function mutation or disruption can be in IFNAR1, JAK2, or B2M. The methods include the intratumoral administration of nanoplexed poly(TC) formulations. These methods are further useful for a variety of therapeutic methods and uses relating to the administration of an immune checkpoint therapy such as anti-PD 1 or anti-PDL1 for the prevention of, and/or against the occurrence of cancer, particularly solid cancer.

公开(公告)号：US20200163966A1

公开(公告)日：2020-05-28

申请号：US16625075

申请日：2018-06-27

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Thomas G. GRAEBER ,  Jennifer TSOI ,  Antoni RIBAS ,  Lidia ROBERT ,  Nicolaos PALASKAS

IPC: A61K31/517 ,  A61K35/17 ,  A61K31/437 ,  C07K16/28

Abstract: The current methods and compositions provide for a novel therapeutic method for treating patients diagnosed with melanoma, especially those that have become resistant to certain other therapies. Accordingly, certain aspects of the disclosure relate to a method for treating melanoma in a subject, the method comprising administering a composition comprising a ferroptosis-inducing agent or other dedifferentiated melanoma-targeting agent to the subject.

公开(公告)号：US20200000851A1

公开(公告)日：2020-01-02

申请号：US16568116

申请日：2019-09-11

Applicant: The Regents of the University of California

Inventor： Theodore Lee ROTH ,  Eric SHIFRUT ,  Alexander MARSON ,  Cristina Puig SAUS ,  Antoni RIBAS

IPC: A61K35/17 ,  C12N15/85 ,  C12N15/90 ,  C12N9/22 ,  C12N15/113 ,  C07K14/725

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20190076399A1

公开(公告)日：2019-03-14

申请号：US16084911

申请日：2017-03-16

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. LO ,  Willy HUGO ,  Antoni RIBAS ,  Jesse ZARETSKY

IPC: A61K31/385 ,  A61P35/00 ,  A61K39/395 ,  A61K31/337 ,  A61K31/427 ,  C12Q1/686

Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

公开(公告)号：US20160123964A1

公开(公告)日：2016-05-05

申请号：US14933853

申请日：2015-11-05

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Paul C. TUMEH ,  Antoni RIBAS

IPC: G01N33/50 ,  A61K39/395 ,  A61K35/15 ,  C07K16/28

CPC classification number: G01N33/5091 ,  A61K2039/505 ,  C07K16/2818 ,  C07K2317/76 ,  G01N2800/52

Abstract: A method of analyzing a biological sample from a subject that has a tumor or cancer, comprising: determining, for target cells having a phenotype of interest spatial resolution of the target cells, density of the spatially resolved target cells in the sample; and proximity between spatially resolved target cells of interest in the sample; and determining an overall score based at least in part on the preceding parameters. A method for identifying a patient as a responder to single agent anti-PD-1 or anti-PD-L1 therapy is provided. Similar methods are provided for detecting adaptive immune resistance, the presence of cancer in a patient sample, determining efficacy of cancer therapy, and determining response to and monitoring the efficacy of cancer therapy.

Abstract translation: 一种从具有肿瘤或癌症的受试者分析生物样品的方法，包括：对于具有目标细胞的感兴趣空间分辨率的靶细胞，确定样品中空间分辨的靶细胞的密度; 以及样品中感兴趣的空间分辨的靶细胞之间的接近度; 以及至少部分地基于前述参数来确定总分。 提供了将患者识别为单剂抗PD-1或抗PD-L1治疗的应答​​者的方法。 提供了类似的方法用于检测适应性免疫耐受性，患者样品中存在癌症，确定癌症治疗的功效，以及确定对癌症治疗的疗效的响应和监测。

公开(公告)号：US20220241336A1

公开(公告)日：2022-08-04

申请号：US17725478

申请日：2022-04-20

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Theodore Lee ROTH ,  Eric SHIFRUT ,  Alexander MARSON ,  Cristina PUIG SAUS ,  Antoni RIBAS

IPC: A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20210161943A1

公开(公告)日：2021-06-03

申请号：US17048473

申请日：2019-04-16

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Antoni RIBAS ,  Gabriel Abril RODRIGUEZ ,  Catherine Grasso ,  Davis Y. TORREJON

IPC: A61K31/7105 ,  A61P35/00 ,  C07K16/28 ,  A61K45/06

Abstract: Disclosed herein are methods of treating cancer in a subject, comprising: administering at least one PAK4 inhibitor to the subject; and in certain embodiments administering at least one immunostimulatory agent to the subject. In some aspects, the immunostimulatory agent can be a checkpoint inhibitor. In certain aspects the checkpoint inhibitor can be an anti-PD1 antibody.

公开(公告)号：US20190262343A1

公开(公告)日：2019-08-29

申请号：US16312893

申请日：2017-06-21

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Antoni RIBAS ,  Helena ESCUIN-ORDINAS

IPC: A61K31/517 ,  A61P17/02 ,  A61K31/4375 ,  A61K31/506 ,  A61K31/519 ,  A61K31/4409 ,  A61K31/454 ,  A61K31/4184 ,  A61K9/00 ,  A61K9/06

Abstract: Methods for treating a wound are provided herein. Such methods include a step of contacting the wound with an effective amount of a BRAF inhibitor. In some aspects, BRAF inhibitors may be part of a pharmaceutical composition. In such case, the pharmaceutical composition may include an effective amount of a BRAF inhibitor and a pharmaceutically acceptable carrier. In certain aspects, the pharmaceutical composition is a topical agent comprising an ointment, cream liquid, gel, hydrogel, or a spray. Further, in some embodiments, a BRAF inhibitor or a pharmaceutical composition thereof may be part of wound dressing for use in treating a wound. In this case, the wound dressing may be impregnated or coated with the BRAF inhibitor or pharmaceutical composition thereof.