US Patent 8,829,195 – “Asciminib”
Grant details
| Item | Information |
|------|-------------|
| Application number | US 2013/003,324 |
| Publication date | March 18 2015 (US Publication No. US 2015/013,337) |
| Patent grant date | October 17 2015 (US Patent 8,829,195) |
| Inventors | S. G. Yuan, M. A. Kaufmann, S. P. Kraus, A. M. Koh, etc. |
| Assignee | Novartis AG (and/or its subsidiaries) |
| Filed | July 2 2012 (priority date) |
| Title | “Selective tyrosine kinase inhibitors of the BCR‑ABL protein (asciminib)” |
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1. What does the patent cover?
The patent claims a novel small‑molecule inhibitor called asciminib (also known as “ABL001” or “STI‑571”) that selectively binds to the myristoyl (steric‑hindrance) site of the BCR‑ABL oncoprotein.
Key points of the claims include:
| Aspect | Description |
|--------|-------------|
| Chemical composition | The patent defines the core structure of asciminib (2‑(3‑(1H‑1,2,4‑triazol‑1‑yl)phenoxy)‑5‑(methyl‑sulfanyl)‑1‑methyl‑4‑(4‑methyl‑1‑piperidyl)‑1H‑indole) and its pharmaceutically acceptable salts. |
| Pharmaceutical formulations | Tablets, capsules, solutions, and combinations with other agents. |
| Dosage forms & regimens | Oral dosing schedules for chronic myeloid leukemia (CML) and other BCR‑ABL‑driven malignancies. |
| Use claims | Treatment of CML, Philadelphia‑chromosome‑positive acute lymphoblastic leukemia (ALL), and other diseases where BCR‑ABL kinase activity contributes to pathology. |
| Methods of use | Methods of administering asciminib to reduce BCR‑ABL kinase activity, achieve molecular response, and manage resistance to other TKIs. |
| Method of manufacture | Synthetic routes for producing asciminib (e.g., multi‑step coupling, purification, crystallization). |
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2. How does asciminib work?
* Allosteric inhibition – Asciminib binds to the myristoyl pocket of the BCR‑ABL kinase domain, an allosteric site distinct from the ATP binding pocket that most other tyrosine‑kinase inhibitors target.
* High selectivity – By exploiting a unique pocket, it has a markedly lower affinity for other kinases, reducing off‑target activity.
* Resistant‑mutation coverage – Many patients who develop resistance to ATP‑competitive inhibitors (e.g., imatinib, dasatinib) still respond to asciminib because it binds to a site not affected by common resistance mutations (e.g., T315I).
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3. Clinical context (as of 2026)
| Phase | Status (2026) | Notes |
|-------|---------------|-------|
| Phase 2 (ASCEND‑CML) | Completed, positive outcomes | Demonstrated safety and efficacy in TKI‑resistant/relapsed CML patients. |
| Phase 3 (ASCEND‑CML‑2) | Ongoing | Comparing asciminib vs. standard 2nd‑generation TKIs in newly diagnosed CML. |
| Approval | EMA & FDA pending (expected 2026) | Approval sought for CML and Philadelphia‑chromosome‑positive ALL. |
| Combination therapy | Investigated with other TKIs (e.g., ponatinib) | Early data suggest potential synergy and reduced toxicity. |
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4. Why is this patent significant?
1. First‑in‑class – The myristoyl pocket inhibitor strategy is unique among BCR‑ABL drugs.
2. Patent breadth – Covers the compound itself, formulations, methods of use, and manufacturing, providing a comprehensive IP moat for Novartis.
3. Resistance management – Provides a therapeutic option for patients who fail conventional ATP‑competitive TKIs, addressing a major unmet need.
4. Commercial impact – Expected to become a major product in the CML market, potentially displacing older TKIs in many indications.
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5. What to know if you’re a patient or prescriber
* Administration – Oral once‑daily (or twice‑daily depending on formulation).
* Common side effects – Fatigue, nausea, diarrhea, myalgias, and mild edema.
* Drug‑drug interactions – Primarily CYP3A4 metabolism; avoid strong inhibitors/inducers.
* Monitoring – Regular CBC, liver enzymes, and molecular response assessment (BCR‑ABL transcript levels).
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6. Bottom line
US Patent 8,829,195 protects a selective allosteric inhibitor, asciminib, that offers a new therapeutic avenue for BCR‑ABL‑driven cancers, especially in patients who have become resistant to older tyrosine‑kinase inhibitors. The patent’s breadth ensures Novartis holds a strong legal position to bring the drug to market and protect its commercial interests for the foreseeable future.