Truncated IL-28 and IL-29 Mutants for Reduced Toxicity
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Solution Overview
Problem
Current therapies for autoimmune disorders like multiple sclerosis are limited by toxicity, side effects, and desensitization issues with long-term use, necessitating the development of safer and more effective treatments.
Innovation Solution
Administration of IL-28A, IL-28B, or IL-29 compositions as monotherapy or in combination with other treatments to enhance immune responses and reduce tumor growth, leveraging their antiviral and immune regulatory activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies (corticosteroid drugs, IFN-β, Novantrone) are used to treat multiple sclerosis, then immune response modulation is achieved, but toxicity and cytotoxic side effects increase
Solution Approach 1:
The patent modifies the chemical structure of interferon beta by creating truncated variants (e.g., residues 1-166, 1-170, 1-174) and engineered mutants with altered amino acid sequences. These parameter changes in the protein structure reduce cytotoxicity while preserving immunomodulatory activity, directly resolving the contradiction between therapeutic effectiveness and toxicity.
Solution Approach 2:
The patent extracts and removes the toxic C-terminal portion of the interferon beta molecule, retaining only the essential N-terminal functional domains (residues 1-166, 1-170, or 1-174). This extraction eliminates the harmful cytotoxic effects while preserving the beneficial immune regulatory functions.
2Duration of action of moving object
If continuous use of current MS therapies is implemented, then symptom management is improved, but patient desensitization occurs limiting long-term use
Solution Approach 1:
The patent creates a dynamic therapeutic approach by engineering interferon beta variants with modified amino acid sequences that adapt the protein's interaction with immune cells. These dynamic structural modifications prevent receptor desensitization and maintain therapeutic responsiveness over extended treatment periods, enabling long-term use without loss of efficacy.
3Productivity
If high doses of Novantrone are administered to achieve maximal therapeutic effects, then tumor growth inhibition is enhanced, but cytotoxic side effects and toxicity increase
Solution Approach 1:
The patent engineers interferon beta mutants with specific amino acid substitutions that enhance antitumor activity while reducing cytotoxicity. These parameter changes in the protein structure allow for effective tumor growth inhibition at lower, safer doses, resolving the contradiction between productivity and harmful effects.
Data Source
AI summary
Methods for treating patients with cancer and autoimmune disorders using IL-28 and IL-29 molecules. The IL-28 and IL-29 molecules include polypeptides that have homology to the human IL-28 or IL-29 polypeptide sequence and proteins fused to a polypeptide with IL-28 and IL-29 functional activity. The molecules can be used as a monotherapy or in combination with other known cancer and/or autoimmune therapeutics.