Revolutionized Cryopreserved Tumor Infiltrating Lymphocyte Revitalization

Publication ID: 24-11857573_0005_PTD
Published: October 28, 2025
Category:Future Evolutions & Paradigm Shifts

Legal Citation

pr1or.art Inc., “Revolutionized Cryopreserved Tumor Infiltrating Lymphocyte Revitalization,” Published Technical Disclosure No. 24-11857573_0005_PTD, Published October 28, 2025, available at https://archive.pr1or.art/24-11857573_0005_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. 11,857,573.

Summary of the Inventive Concept

A next-generation approach to revitalizing cryopreserved tumor infiltrating lymphocytes, incorporating advanced restimulation protocols, novel cytokine cocktails, and dynamically controlled bioreactors to enhance efficacy and scalability in adoptive cell therapy.

Background and Problem Solved

The original patent, 'Restimulation of cryopreserved tumor infiltrating lymphocytes', demonstrated the potential of adoptive transfer of TILs in treating bulky, refractory cancers. However, the current approach has limitations in terms of TIL expansion, cryopreservation, and infusion. The new inventive concept addresses these limitations by introducing a paradigm shift in TIL revitalization, enabling more efficient, scalable, and effective treatment options.

Detailed Description of the Inventive Concept

The inventive concept comprises a system for revitalizing cryopreserved TILs, incorporating an aerobic-to-anaerobic metabolic shift inducer, novel cytokine cocktails, and dynamically controlled bioreactors. The method involves cryopreserving TILs, thawing and restimulating them with the cytokine cocktail, and expanding the restimulated lymphocytes in the bioreactor. The device features a chamber for culturing the lymphocytes, a microfluidic system for delivering the restimulation protocol, and a sensor for monitoring the metabolic state of the lymphocytes. The composition for adoptive cell therapy includes the expanded TILs and a cryopreservative solution containing a metabolic modulator, enhancing the in vivo longevity of the lymphocytes. The computer-implemented method optimizes restimulation protocols based on lymphocyte characteristics and predictive modeling.

Novelty and Inventive Step

The new claims introduce a novel cytokine cocktail, aerobic-to-anaerobic metabolic shift inducer, and dynamically controlled bioreactors, which are not obvious from the original patent. The inventive concept's emphasis on metabolic modulation, sensor-enabled monitoring, and predictive modeling-based optimization represents a significant departure from the current state of the art.

Alternative Embodiments and Variations

Alternative embodiments may include variations in the cytokine cocktail composition, bioreactor design, and sensor types. Additionally, the inventive concept could be adapted for use with other types of immune cells or in combination with other cancer therapies.

Potential Commercial Applications and Market

The revolutionary TIL revitalization approach has significant commercial potential in the adoptive cell therapy market, targeting patients with bulky, refractory cancers. The inventive concept's scalability and efficacy enhancements position it for widespread adoption in cancer treatment centers and biotech companies.

Field of Art

Immunotherapy, cell biology, and cancer treatment, specifically focused on tumor infiltrating lymphocyte (TIL) expansion and cryopreservation techniques. A PHOSITA would have advanced training in cellular immunology, biotechnology, and regenerative medicine, with expertise in cell culture, cryopreservation protocols, and adoptive cell therapy

Person of Ordinary Skill (PHOSITA) Profile

A researcher or biotechnology professional with a PhD in immunology or related field, experienced in cell manipulation techniques, familiar with TIL expansion methods, and knowledgeable about metabolic modulation in immune cell cultures

Obviousness Rationale

The PTD represents a predictable extension of the source patent's TIL restimulation techniques by introducing incremental improvements in metabolic monitoring, cytokine stimulation, and expansion protocols. A PHOSITA would recognize these variations as logical refinements to existing TIL cryopreservation and expansion methodologies. The proposed innovations represent standard engineering approaches to optimizing cellular therapies through controlled environmental and nutritional interventions.

Obvious Combinations & Variations

Source Patent Element
Cryopreservation and thawing of tumor infiltrating lymphocytes
PTD Variation
Introduction of aerobic-to-anaerobic metabolic shift inducer and dynamically controlled bioreactors
Obviousness Reasoning
Metabolic modulation of immune cells is a known technique in cell biology, and optimizing cellular expansion conditions represents a predictable design choice for improving TIL viability and proliferation
Source Patent Element
First expansion of cryopreserved TILs from tumor digest
PTD Variation
Novel cytokine cocktail and microfluidic delivery system for restimulation
Obviousness Reasoning
Developing alternative cytokine combinations is a routine optimization strategy in immunotherapy, with finite predictable approaches to enhancing lymphocyte activation
Source Patent Element
Harvesting and transferring expanded TIL populations
PTD Variation
Computer-implemented predictive modeling for restimulation protocol optimization
Obviousness Reasoning
Computational approaches to cell culture optimization are well-established in biotechnology, representing an obvious application of machine learning to cellular expansion techniques
Source Patent Element
Cryopreservation of TIL populations in infusion bags
PTD Variation
Cryopreservative solution containing metabolic modulators to enhance in vivo lymphocyte longevity
Obviousness Reasoning
Modifying cryopreservation solutions to improve cellular survival is a predictable engineering solution in cell therapy development
Source Patent Element
Tumor infiltrating lymphocyte expansion method
PTD Variation
Sensor-enabled metabolic state monitoring during lymphocyte culture
Obviousness Reasoning
Real-time cellular monitoring is a standard technique in biotechnology, representing an obvious approach to improving cell culture precision and understanding
35 U.S.C. § 103 Summary: Based on the teachings of US Patent 11857573 and the disclosed technical variations, a Person Having Ordinary Skill In The Art would find the claimed innovations obvious and lacking inventive step. The proposed modifications to TIL restimulation and expansion represent predictable engineering solutions within the existing knowledge of cellular immunotherapy, thereby rendering potential patent claims obvious and unpatentable under 35 U.S.C. Section 103.

Original Patent Information

Patent NumberUS 11,857,573
TitleRestimulation of cryopreserved tumor infiltrating lymphocytes
Assignee(s)Iovance Biotherapeutics, Inc.