Anti-CD38 Antibody and Lenalidomide Combination Therapy

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Solution Overview

Problem

Current treatments for multiple myeloma, including proteasome inhibitors and chemotherapy, eventually lead to resistance, resulting in a median survival of only 3 to 5 years, highlighting the need for new and efficacious therapies that can extend survival and improve outcomes for patients with this blood cancer.

Innovation Solution

Administering anti-CD38 antibodies, such as hu38SB19, in combination with lenalidomide, which are capable of killing CD38+ cells through apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC), potentially synergizing their effects to enhance treatment efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies (proteasome inhibitors, immunomodulatory drugs, chemotherapy) are administered, then survival is improved, but resistance develops and survival remains limited to 3-5 years

Engineering Contradiction:

Improvetreatment efficacyVSAvoidsurvival duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent combines anti-CD38 antibodies with lenalidomide (an immunomodulatory drug) to create a synergistic treatment regimen. This combination therapy merges two different mechanisms of action: CD38-targeted antibody therapy and immunomodulation, aiming to overcome resistance and extend survival beyond what either treatment achieves alone.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If anti-CD38 antibodies are administered, then tumor cell killing is achieved through apoptosis, ADCC, and CDC, but treatment resistance may still develop

Engineering Contradiction:

Improvetreatment efficacyVSAvoidresistance development

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines anti-CD38 antibodies with lenalidomide to create a treatment regimen that attacks multiple pathways simultaneously. The antibody provides direct tumor cell killing through apoptosis, ADCC, and CDC, while lenalidomide adds immunomodulatory effects, creating a multi-faceted approach that reduces the likelihood of resistance development compared to single-agent therapy.

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination of anti-CD38 antibodies and lenalidomide demonstrates significant anti-tumor activity, inhibiting tumor growth more effectively than either treatment alone, as shown in xenograft models, indicating a potential for improved survival and treatment outcomes for multiple myeloma patients.

Implementation Method 1

capable of killing a CD38+ cell by apoptosis

Methodology Applied

Scientific EffectApoptosis:

Implementation Method 2

antibody-dependent cell-mediated cytotoxicity (ADCC)

Methodology Applied

Scientific EffectAntibody-dependent cell-mediated cytotoxicity (ADCC):

Implementation Method 3

complement-dependent cytotoxicity (CDC)

Methodology Applied

Scientific EffectComplement-dependent cytotoxicity (CDC):

Data Source

PatentEP2928495B1Compositions comprising Anti-CD38 antibodies and lenalidomide

Publication Date: 2019.03.27 SANOFI SA(FR)

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Figure 2A

AI summary

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and lenalidomide compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.