Genetically Engineered T Cells with Regnase-1 and/or TGFBRII Disruption for Neurodegenerative Diseases and Beyond

Publication ID: 24-11857574_0007_PTD

Published: October 28, 2025

Category:New Applications & Use Cases

Legal Citation

pr1or.art Inc., “Genetically Engineered T Cells with Regnase-1 and/or TGFBRII Disruption for Neurodegenerative Diseases and Beyond,” Published Technical Disclosure No. 24-11857574_0007_PTD, Published October 28, 2025, available at https://archive.pr1or.art/24-11857574_0007_PTD

This technical disclosure describes improvements that would be readily apparent to a Person Having Ordinary Skill In The Art (PHOSITA) when considered in combination with the foundational architecture disclosed in U.S. Patent No. 11,857,574.

Summary of the Inventive Concept

This inventive concept leverages the core technology of genetically engineered T cells with Regnase-1 and/or TGFBRII disruption to target novel applications in neurodegenerative diseases, autoimmune diseases, and cancer stem cell therapy, demonstrating the versatility and broad potential of this innovative approach.

Background and Problem Solved

The original patent disclosed genetically engineered T cells with Regnase-1 and/or TGFBRII disruption for improved functionality and persistence in cancer immunotherapy. However, this technology has untapped potential in other fields. Neurodegenerative diseases, autoimmune diseases, and cancer stem cell therapy are areas where targeted therapies are urgently needed. The inventive concept addresses these limitations by adapting the core technology to these new applications.

Detailed Description of the Inventive Concept

The inventive concept involves genetically engineering T cells with Regnase-1 and/or TGFBRII disruption to target specific disease mechanisms. For neurodegenerative diseases, the T cells are engineered to express neurotrophic factors, promoting neural cell survival and regeneration. In autoimmune diseases, the T cells are designed to express cytokines that promote immune tolerance, reducing autoimmune responses. In cancer stem cell therapy, the T cells are engineered to express chimeric antigen receptors (CARs) targeted to cancer stem cell antigens and proteins that promote differentiation of cancer stem cells into non-cancerous cells. The CRISPR/Cas-mediated gene editing system is used to disrupt Regnase-1 and/or TGFBRII genes, and the T cells are administered to patients in need or expanded ex vivo using bioreactors and cytokine-supplemented media.

Novelty and Inventive Step

The inventive concept's novelty lies in its application of the core technology to new disease areas, leveraging the improved functionality and persistence of genetically engineered T cells with Regnase-1 and/or TGFBRII disruption. The inventive step involves adapting the gene editing system and T cell engineering strategies to target specific disease mechanisms, demonstrating a non-obvious and innovative approach to addressing unmet medical needs.

Alternative Embodiments and Variations

Alternative embodiments of the inventive concept include using different gene editing systems, such as base editing or prime editing, to disrupt Regnase-1 and/or TGFBRII genes. Variations may also include using different types of immune cells, such as natural killer cells or dendritic cells, or combining genetically engineered T cells with other therapies, such as checkpoint inhibitors or small molecule drugs.

Potential Commercial Applications and Market

The inventive concept has significant commercial potential in the fields of neurodegenerative diseases, autoimmune diseases, and cancer stem cell therapy. The market for these applications is substantial, with a growing demand for targeted and effective therapies. The inventive concept's versatility and broad potential make it an attractive opportunity for companies and investors seeking to develop innovative treatments for unmet medical needs.

Section 103 Obviousness Analysis (PHOSITA)

▼

Field of Art

Immunotherapy, genetic engineering of immune cells, CRISPR/Cas gene editing, with expertise in molecular biology, cell engineering, and therapeutic cell modification techniques

Person of Ordinary Skill (PHOSITA) Profile

A PhD-level researcher with advanced training in immunology, molecular genetics, and cell therapy, familiar with CRISPR gene editing, CAR T-cell technologies, and techniques for modifying immune cell functionality

Obviousness Rationale

A PHOSITA would recognize that the core technology of genetically disrupting Regnase-1 and TGFBRII in T cells represents a versatile platform technology with broad applicability beyond the original cancer therapy context. The source patent establishes a fundamental genetic modification strategy that can be readily adapted to different disease contexts by modifying the expressed genes or targeting approach. The PTD demonstrates predictable extensions of the core gene editing technique to neurodegenerative, autoimmune, and cancer stem cell applications using standard molecular biology techniques.

Obvious Combinations & Variations

Source Patent Element

CRISPR/Cas-mediated gene editing of Regnase-1 and TGFBRII in T cells

PTD Variation

Applying the gene editing technique to T cells targeting neurodegenerative diseases by expressing neurotrophic factors

Obviousness Reasoning

A PHOSITA would recognize that the core gene editing methodology is transferable across disease contexts, with predictable results of modifying T cell functionality through targeted genetic modifications

Source Patent Element

Chimeric antigen receptor (CAR) T-cell engineering approach

PTD Variation

Extending CAR T-cell design to target cancer stem cell antigens with additional differentiation-promoting genes

Obviousness Reasoning

Modifying CAR design to include additional therapeutic genes represents a known technique for expanding therapeutic potential, using standard molecular cloning and gene insertion strategies

Source Patent Element

Genetic disruption of immunoregulatory genes to enhance T cell functionality

PTD Variation

Using genetically engineered T cells to promote immune tolerance in autoimmune disease contexts

Obviousness Reasoning

Redirecting the immunomodulatory mechanism to suppress rather than activate immune responses is a predictable variation within the established gene editing framework

Source Patent Element

Ex vivo T cell manipulation and genetic modification techniques

PTD Variation

Developing specialized bioreactor systems for expanding genetically modified T cells

Obviousness Reasoning

Optimizing cell culture conditions for engineered T cells represents a standard engineering approach with predictable optimization strategies known in the field

Source Patent Element

CRISPR/Cas gene editing targeting specific gene regions

PTD Variation

Exploring alternative gene editing systems like base editing and prime editing

Obviousness Reasoning

Investigating alternative gene editing technologies represents an obvious extension of the core CRISPR methodology, driven by ongoing technological improvements in the field

35 U.S.C. § 103 Summary: Based on the teachings of US Patent 11857574, a person of ordinary skill in the art would find the variations disclosed in this publication obvious, as they represent predictable extensions of the core gene editing and T cell modification technology. The disclosed methods demonstrate routine application of known genetic engineering techniques to novel disease contexts, utilizing standard molecular biology approaches that would be apparent to a skilled practitioner in the field of immunotherapy and genetic cell modification.

Original Patent Information

Patent Number	US 11,857,574
Title	Genetically engineered T cells with Regnase-1 and/or TGFBRII disruption have improved functionality and persistence
Assignee(s)	CRISPR THERAPEUTICS AG