Bispecific Antibody Interferon ADC Combination Therapy

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Solution Overview

Problem

Current bispecific antibodies and interferons face challenges with short circulation half-life, systemic toxicity, and suboptimal responses in patients, while antibody-drug conjugates have limitations in stability and pharmacokinetic properties, necessitating the development of improved combinations for enhanced immune response against diseases like cancer and infectious diseases.

Innovation Solution

Combination therapies using leukocyte-redirecting bispecific antibodies, interferons, and antibody-drug conjugates (ADCs) to induce or enhance immune responses, with specific designs such as DOCK-AND-LOCK™ complexes and DNL™ constructs for improved stability and efficacy, and the use of checkpoint inhibitor antibodies to enhance treatment effectiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If bisspecific antibodies and interferons are used for immune response induction, then immune response is enhanced, but circulation half-life is short

Engineering Contradiction:

Improvecirculation half-lifeVSAvoidimmune response effectiveness

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent combines interferons with antibody-drug conjugates (ADCs) into a single therapeutic composition. The interferon component enhances immune response while the ADC provides targeted delivery and prolonged circulation. This merging allows the short half-life limitation of interferons to be overcome by the pharmacokinetic properties of the ADC carrier, while maintaining the immune-enhancing benefits.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite therapeutic agent comprising both interferon and ADC components. This composite structure allows the interferon to exert its immunomodulatory effects while the ADC portion provides stable pharmacokinetics and targeted delivery. The composite nature resolves the contradiction by integrating the strengths of both agents while mitigating their individual weaknesses.

Inventive Principle:

Principle #40Composite materials

2Reliability

If bisspecific antibodies and interferons are used to enhance immune response, then treatment effectiveness improves, but systemic toxicity increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidsystemic toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody-drug conjugate acts as an intermediary vehicle that delivers the interferon specifically to target sites. The ADC component provides targeted delivery through its antibody moiety, which directs the interferon to diseased cells or tissues. This intermediary approach allows the interferon to exert its full immunomodulatory effect at the target site while minimizing exposure to healthy tissues, thereby reducing systemic toxicity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention implements local quality by concentrating the interferon therapeutic effect at the target site through ADC-mediated targeted delivery. The interferon is delivered with high concentration to the diseased tissue where it is needed for immune response enhancement, while systemic circulation levels remain low. This spatial differentiation of drug concentration resolves the contradiction between treatment effectiveness and systemic toxicity.

Inventive Principle:

Principle #3Local quality

3Stability of the object's composition

If antibody-drug conjugates are used for targeted therapy, then stability improves, but pharmacokinetic properties are suboptimal

Engineering Contradiction:

Improvetherapeutic composition stabilityVSAvoidpharmacokinetic performance

Core Design Contradiction:

Stability of the object's compositionVSDuration of action of moving object

Solution Approach 1:

The invention optimizes pharmacokinetic parameters by carefully selecting and adjusting the ADC component characteristics, including antibody isotype, drug-to-antibody ratio, and linker chemistry. These parameter changes allow the ADC portion to provide prolonged circulation half-life and stable pharmacokinetics, compensating for the inherent limitations of interferon while maintaining the stability of the overall therapeutic composition.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS10111954B2Combination therapy for inducing immune response to disease

Publication Date: 2018.10.30 IBC PHARMACEUTICALS INC

AI summary

The present invention concerns combinations of two or more agents for inducing an immune response to cancer or infectious disease. Agents may include leukocyte redirecting complexes, antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The leukocyte redirecting complexes have at least one binding site for a leukocyte antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3× anti-CD19 bispecific antibody, although antibodies against other leukocyte antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of cells associated with cancer or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.