Anti-CD38 Antibody and Melphalan Combination for Multiple Myeloma

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Solution Overview

Problem

Current treatments for multiple myeloma, including therapies targeting CD38, have limited efficacy and do not provide a cure, leading to relapse and poor prognosis for patients with CD38-expressing tumors.

Innovation Solution

A synergistic combination of an anti-CD38 antibody with melphalan, a nitrogen mustard alkylating agent, which demonstrates enhanced efficacy in reducing bone lysis in multiple myeloma models, offering a promising approach for treating multiple myeloma and other leukemias.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current chemotherapy protocols including CD38-targeting antibodies are used, then complete remission rate is improved, but overall survival remains limited and relapse occurs

Engineering Contradiction:
Improvecomplete remission rateVSAvoidoverall survival
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent combines anti-CD38 antibodies with melphalan (a nitrogen mustard alkylating agent) to create a synergistic combination therapy. This merging of two different therapeutic mechanisms (antibody-mediated targeting and alkylating chemotherapy) achieves both improved complete remission rates and extended overall survival, resolving the contradiction between initial remission efficacy and long-term survival durability.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If high dose chemotherapy followed by stem cell transplantation is used, then complete remission rate increases, but overall survival is only slightly prolonged

Engineering Contradiction:
Improvecomplete remission rateVSAvoidoverall survival
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the therapeutic parameters by introducing a combination regimen that integrates antibody therapy with alkylating agent chemotherapy at optimized dosages. This parameter change achieves superior synergistic effects compared to high-dose chemotherapy alone, improving both complete remission rates and overall survival duration without requiring stem cell transplantation.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If maintenance therapy with interferon-alpha is used, then relapse prevention is attempted, but no evidence for cure is obtained

Engineering Contradiction:
Improveremission durationVSAvoidcure evidence
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent creates a composite therapeutic approach by combining anti-CD38 antibodies with melphalan, creating a multi-mechanism regimen that addresses both tumor cell killing and immune modulation. This composite therapy provides durable remission with evidence of cure potential, overcoming the limitations of interferon-alpha maintenance therapy.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP2900232B1Combinations and uses thereof
Publication Date: 2017.11.15 MORFOZIS AG
  • EP2900232B1 patent drawingFigure 1
  • EP2900232B1 patent drawingFigure 2
  • EP2900232B1 patent drawingFigure 3

AI summary

The present disclosure describes a pharmaceutical combination of an anti-CD38 antibody and melphalan.