United States Patent 9,732,058: Osimertinib Claim Scope, Orange Book Status, Litigation Risk and Patent Landscape
US Patent No. 9,732,058 protects a narrow chemical genus centered on osimertinib, the active ingredient in AstraZeneca’s Tagrisso. The patent covers four defined substitution patterns, pharmaceutical compositions containing those compounds, and treatment of lung cancer, including non-small cell lung cancer (NSCLC). The patent was issued on August 15, 2017, and has a 2032 patent-term endpoint based on its US filing chain. Its commercial importance is high because the principal claimed molecule is osimertinib mesylate, Tagrisso’s active pharmaceutical ingredient.
What compounds does US Patent 9,732,058 protect?
The independent compound claim does not cover a broad, open-ended Markush structure. It fixes most substituents and permits only two alternatives at two positions:
The mathematical scope of claim 1 is four expressly permitted compound combinations. Claims 2 and 3 identify two specific compounds within that scope.
The claimed chemical architecture contains four commercially relevant elements:
- An acrylamide warhead capable of covalent interaction with mutant EGFR Cys797.
- A substituted aniline core containing methoxy and aminoalkyl groups.
- A pyrimidine linker.
- An indole substituent, including the 1-methylindole group present in osimertinib.
The claims therefore target a fourth-generation-style irreversible kinase inhibitor architecture, although osimertinib is generally classified as a third-generation EGFR tyrosine kinase inhibitor.
What is the relationship between the claimed compounds and osimertinib?
Claim 3 covers osimertinib, also known as AZD9291:
N-(4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}-2-[methyl-(2-methylaminoethyl)amino]-phenyl)prop-2-enamide
Tagrisso is marketed as osimertinib mesylate. The claim covers the free base and pharmaceutically acceptable salts, which places osimertinib mesylate within the express salt coverage of claims 1 and 3.
Claim 2 covers the corresponding non-N-methyl indole and dimethylaminoethyl analog:
N-(2-[2-dimethylaminoethyl-methylamino]-5-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-4-methoxyphenyl)-prop-2-enamide
That compound is not the principal commercial Tagrisso active ingredient, but it is relevant to freedom-to-operate analysis because claim 1 reaches it directly.
How broad are the composition claims in US Patent 9,732,058?
Claim 4 covers pharmaceutical compositions containing any compound within claims 1 through 3, or a pharmaceutically acceptable salt, with a pharmaceutically acceptable diluent or carrier.
The composition claim is structurally dependent on the compound claims. It does not independently protect every osimertinib formulation. It requires the presence of a claimed active compound but does not recite:
- A particular tablet strength;
- A specific excipient;
- A particular release profile;
- A particle-size distribution;
- A polymorphic form;
- A manufacturing process;
- A specific fixed-dose combination; or
- A particular dosage regimen.
A generic product containing chemically identical osimertinib mesylate would face both the compound claims and claim 4. A formulation materially different from Tagrisso could still infringe claim 4 if it contains a claimed compound or salt.
What formulations are protected by the patent?
The patent protects compositions at a functional level rather than a detailed formulation level. A conventional immediate-release tablet, capsule, suspension or other dosage form can fall within claim 4 if it contains the claimed compound or salt.
The claim does not appear to require the specific Tagrisso tablet formulation. Separate formulation, salt, solid-state, manufacturing or dosage patents would therefore be important in a generic-entry analysis. A competitor that avoids a formulation patent may still infringe the 9,732,058 compound or composition claims.
What methods of treatment are covered?
Claim 5 covers administration of a claimed compound or salt to treat lung cancer in a warm-blooded animal. Claim 6 narrows that method to NSCLC.
The method claims contain the following limitations:
| Limitation |
Scope |
| Patient |
Warm-blooded animal |
| Disease |
Lung cancer |
| Subclass |
Non-small cell lung cancer in claim 6 |
| Active agent |
Any compound of claims 1 to 3 or pharmaceutically acceptable salt |
| Administration |
Effective amount |
The claims do not expressly limit treatment to EGFR-mutated tumors, T790M-positive disease, a particular line of therapy, or a specific dose. The absence of those limitations gives the method claims potentially broad literal coverage, subject to patentability, written-description, enablement and claim-construction issues.
The claims do not expressly cover other approved Tagrisso indications such as adjuvant treatment after tumor resection or unresectable stage III EGFR-mutated NSCLC following chemoradiotherapy. Those indications may be protected by separate method-of-use patents or regulatory exclusivity.
What is the patent term and expiration date?
US Patent 9,732,058 was issued on August 15, 2017. Its priority chain traces to AstraZeneca patent filings directed to osimertinib and related compounds. The relevant US patent term is generally calculated from the earliest effective US nonprovisional filing in the chain, not simply from the foreign priority date.
| Event |
Date |
| Earliest published priority family filing |
February 2011 |
| Relevant US filing chain |
February 2012 |
| Patent issuance |
August 15, 2017 |
| Expected base patent expiration |
February 2032 |
The practical Orange Book endpoint for the core osimertinib patent family is generally reported in February 2032. Any patent-term adjustment, patent-term extension or correction reflected in USPTO or FDA records controls the final enforceable date.
The patent does not provide indefinite protection for every Tagrisso use. Its principal value is the chemical compound and salt coverage, which remains relevant regardless of whether a later formulation or method-of-use patent expires later.
What is the Orange Book status of osimertinib?
Tagrisso is FDA-approved and listed in the Orange Book under osimertinib mesylate. The FDA initially approved Tagrisso in November 2015 for previously treated metastatic EGFR T790M mutation-positive NSCLC under the accelerated approval pathway. FDA later expanded the label to include first-line treatment for metastatic EGFR-mutated NSCLC and adjuvant treatment after tumor resection. FDA also approved Tagrisso with chemotherapy for certain locally advanced or metastatic EGFR-mutated NSCLC patients.[1]
The Orange Book patent estate has included patents directed to:
- Osimertinib and related compounds;
- Pharmaceutical compositions;
- Therapeutic use in EGFR-mutated NSCLC;
- Specific dosing or treatment settings; and
- Later-line or adjuvant treatment indications.
The exact Orange Book listing and expiration entries should be assessed by patent number and use code, because the presence of multiple patents can create different risks for ANDAs seeking all indications versus a section viii carve-out.
Which companies are challenging Tagrisso exclusivity?
Generic osimertinib applicants can challenge listed patents through an abbreviated new drug application (ANDA) containing a Paragraph IV certification. That certification alleges that a listed patent is invalid, unenforceable or not infringed.
Publicly reported ANDA activity involving osimertinib has included challenges by major generic manufacturers, including Teva, Lupin, Sun Pharmaceutical and Dr. Reddy’s Laboratories. AstraZeneca has historically responded to Paragraph IV notices with patent litigation in federal district court.
The commercial impact depends on which patents each applicant challenges. A Paragraph IV challenge to a later-expiring method-of-use patent may not create the same launch opportunity as a challenge to a core compound patent. A generic company may also seek approval for a narrower label that omits patented indications.
What does a Paragraph IV challenge mean for US Patent 9,732,058?
Under the Hatch-Waxman framework, AstraZeneca generally has 45 days after receiving a qualifying Paragraph IV notice to file an infringement action. A timely suit can trigger a 30-month stay of FDA approval, subject to statutory exceptions and court action.[2]
A successful challenge could establish:
- Invalidity for lack of novelty or obviousness;
- Lack of infringement based on a different salt, formulation or claim interpretation;
- Unenforceability based on inequitable conduct or other defenses; or
- A noninfringing carve-out for method-of-use claims.
A generic applicant that directly copies osimertinib mesylate would confront the strongest portion of the patent because claims 1, 3 and 4 reach the active compound, its pharmaceutically acceptable salts and compositions containing them.
What litigation and settlement risks affect generic entry?
The main litigation risk is claim overlap with the core compound claims. A generic manufacturer cannot avoid compound claims merely by using a different excipient or tablet shape. It may need to challenge validity or establish a noninfringing chemical difference.
Settlement agreements can alter the earliest launch date without producing a final invalidity judgment. Common settlement structures include:
- A license for an agreed future launch date;
- A licensed generic arrangement;
- A covenant not to sue for a defined product;
- A carve-out of patented indications; or
- A launch contingent on appellate or regulatory outcomes.
The absence of a final invalidity judgment does not establish that the patent is valid against all future challengers. Patent litigation outcomes are claim-specific and defendant-specific.
How strong is the patent estate for osimertinib?
The estate is strongest where it combines the core chemical patent with later patents covering regulatory uses and product implementation.
| Estate layer |
Business effect |
| Core compound claims |
Highest barrier for an identical active ingredient |
| Salt and composition claims |
Limits alternative presentation of osimertinib |
| Method-of-use claims |
Protects labeled treatment settings |
| Formulation claims |
May delay or narrow product substitution |
| Manufacturing claims |
Can limit process alternatives |
| Regulatory exclusivity |
May block approval independently of patent validity |
US Patent 9,732,058 is commercially stronger than a standalone method-of-use patent because it reaches the active molecule itself. Its narrower chemical definition, however, makes claim construction and prior-art analysis central. A prior-art reference would need to disclose or render obvious the specific combination of the substituted aniline, pyrimidine-indole group, acrylamide and aminoalkyl substituents.
How does the osimertinib patent estate compare with competing EGFR drugs?
| Drug |
Sponsor |
Core modality |
Competitive patent issue |
| Osimertinib, Tagrisso |
AstraZeneca |
Irreversible EGFR inhibitor |
Core compound and use patents extend into the early 2030s |
| Erlotinib, Tarceva |
Genentech/Roche |
Reversible EGFR inhibitor |
Core US patent protection has largely expired |
| Gefitinib, Iressa |
AstraZeneca |
Reversible EGFR inhibitor |
Earlier-generation product with mature generic competition |
| Afatinib, Gilotrif |
Boehringer Ingelheim |
Irreversible ErbB inhibitor |
Separate compound and formulation estate |
| Mobocertinib, Exkivity |
Takeda |
Irreversible EGFR inhibitor |
Commercial and regulatory status differs from Tagrisso |
Osimertinib has a stronger commercial position than earlier EGFR inhibitors because its clinical use expanded across first-line, adjuvant and locally advanced disease settings. Its patent risk is therefore tied to both molecule-level protection and the breadth of the approved label.
What generic launch scenarios exist?
Three scenarios are commercially relevant.
Launch after core patent expiration
A generic applicant could launch broadly after expiration of the core compound patents and resolution of any later-expiring listed patents. This is the lowest litigation-risk scenario but may occur after 2032.
At-risk launch after a successful Paragraph IV challenge
A generic could launch before the listed patent expiration after obtaining a favorable judgment, settlement license or other legal clearance. This creates potential damages exposure if the patent is later upheld.
Carved-out launch
A generic may omit patented indications under section viii and market only nonprotected uses. This strategy is more viable for method-of-use patents than for the core compound claims. It does not avoid infringement of a valid compound patent covering the active ingredient itself.
What manufacturing and geographic barriers remain?
The patent is a US right. Corresponding patents in Europe, Japan, China, Canada and other jurisdictions must be analyzed separately. Expiration dates, prosecution histories, supplementary protection certificates and national claim scope can differ materially.
Manufacturing risk may arise from patents covering:
- Osimertinib intermediates;
- Synthesis routes;
- Crystalline forms;
- Salt formation;
- Purification;
- Impurity control; and
- Tablet manufacture.
A generic manufacturer can avoid a process patent by using a different route, but that route must satisfy regulatory requirements for control of impurities, stereochemistry, residual solvents and batch reproducibility.
What is the revenue exposure from Tagrisso?
Tagrisso is one of AstraZeneca’s largest oncology products. AstraZeneca reported Tagrisso sales of approximately $5.9 billion in 2023.[3] The product’s revenue exposure includes metastatic EGFR-mutated NSCLC, adjuvant therapy and additional approved treatment settings.
Because the product is a high-revenue targeted oncology therapy, an early generic launch would create substantial substitution pressure. The price impact would depend on the number of entrants, the timing of launch, payer substitution rules and whether generic applicants receive approval for the full label.
Key Takeaways
- US Patent 9,732,058 covers a defined set of osimertinib-related compounds and pharmaceutically acceptable salts.
- Claim 3 expressly covers osimertinib, the active moiety in Tagrisso.
- Claim 4 reaches pharmaceutical compositions containing the claimed compounds or salts.
- Claims 5 and 6 cover lung-cancer and NSCLC treatment methods.
- The expected core patent endpoint is in February 2032.
- An identical osimertinib product faces compound, salt and composition claim risk, not merely formulation risk.
- Paragraph IV litigation, settlement licenses and section viii carve-outs are the main pathways to earlier generic entry.
- Later method-of-use, formulation, solid-state and manufacturing patents may extend or complicate the commercial exclusivity analysis.
- Tagrisso’s multibillion-dollar annual sales make the estate strategically important for AstraZeneca and generic challengers.
FAQs
Does US Patent 9,732,058 cover osimertinib mesylate?
Yes. Claim 3 covers the osimertinib free base, and claims 1 and 3 extend to pharmaceutically acceptable salts. Osimertinib mesylate is the active pharmaceutical form used in Tagrisso.
Can a generic avoid US Patent 9,732,058 by using a different excipient?
No, not if the generic contains the claimed osimertinib compound or salt. A different excipient may avoid a separate formulation patent but would not avoid an infringed compound or composition claim.
Does the patent cover every EGFR inhibitor?
No. The claims are limited to the specified acrylamide compounds with defined methoxy, aminoalkyl, pyrimidine and indole substituents. Other EGFR inhibitors fall outside the claims unless their structures satisfy the claim limitations.
Can a generic launch with a carved-out label before 2032?
A carved-out label may avoid particular patented methods of use, but it does not eliminate compound or composition patent risk. For a product containing osimertinib mesylate, the core claims remain the principal barrier.
Are biosimilars relevant to Tagrisso?
No. Tagrisso is a small-molecule drug, not a biologic. The relevant competitors are ANDA-based generic applicants, not biosimilar applicants under the Public Health Service Act.
References
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U.S. Food and Drug Administration. (2024). Tagrisso (osimertinib) prescribing information. FDA.
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U.S. Code. (2023). 21 U.S.C. § 355(j): Abbreviated applications for new drugs.
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AstraZeneca PLC. (2024). Annual report and Form 20-F for the year ended December 31, 2023. AstraZeneca.
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United States Patent and Trademark Office. (2017). U.S. Patent No. 9,732,058: N-(2-[2-dimethylaminoethyl-methylamino]-5-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-4-methoxyphenyl)-prop-2-enamide and related compounds. USPTO.
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
