US Patent 8,946,235: Osimertinib Patent Scope, Claims, Expiration, and Competitive Landscape
US Patent 8,946,235 protects osimertinib, the active pharmaceutical ingredient in Tagrisso, together with its mesylate salt, pharmaceutical compositions, and lung-cancer treatment methods. The patent’s strongest protection is the compound and mesylate-salt claims. The method claims are narrower because they are limited to treatment of lung cancer, with dependent claims directed to non-small cell lung cancer (NSCLC).
The patent was assigned to AstraZeneca and covers the core osimertinib molecule, also known as AZD9291. Its commercial product is TAGRISSO (osimertinib mesylate), marketed by AstraZeneca.[1][2]
What drug does US Patent 8,946,235 protect?
US 8,946,235 protects osimertinib and its pharmaceutically acceptable salts. The claimed molecule is a mutant-selective, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor containing:
- An acrylamide electrophilic warhead;
- A substituted aniline core;
- A dimethylaminoethyl-methylamino side chain;
- A methoxy substituent;
- A 4-(1-methylindol-3-yl)pyrimidin-2-yl amino group.
The marketed active pharmaceutical ingredient is osimertinib mesylate. The free-base chemical name is commonly rendered as:
N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide.
The patent claims include both the free base and the mesylate salt. This distinction is commercially important because Tagrisso tablets contain osimertinib mesylate rather than an unconverted free-base formulation.[2]
How many claims are in US Patent 8,946,235?
The supplied claims contain 12 claims. They divide into four principal categories:
| Claim category |
Claims |
Subject matter |
| Compound and salts |
1 |
Osimertinib or a pharmaceutically acceptable salt |
| Pharmaceutical composition |
2 |
Composition containing the compound or salt |
| Lung-cancer treatment |
3 |
Administration for lung cancer |
| Free-base compound |
4 |
Specifically recited osimertinib free base |
| Free-base composition |
5 |
Composition containing the free base |
| Free-base treatment |
6 |
Lung-cancer treatment using the free base |
| Mesylate salt |
7 |
Osimertinib mesylate |
| Mesylate composition |
8 |
Composition containing osimertinib mesylate |
| Mesylate treatment |
9 |
Lung-cancer treatment using the mesylate |
| NSCLC treatment |
10 |
Claim 3 limited to NSCLC |
| NSCLC treatment |
11 |
Claim 6 limited to NSCLC |
| NSCLC treatment |
12 |
Claim 9 limited to NSCLC |
Claims 1, 4, and 7 are the principal molecular claims. Claims 2, 5, and 8 attach formulation protection to the respective molecular forms. Claims 3, 6, and 9 protect treatment of lung cancer. Claims 10 through 12 narrow those methods to NSCLC.
What is the scope of claim 1?
Claim 1 covers osimertinib and pharmaceutically acceptable salts of osimertinib. It is a product claim, not a method claim. A product claim generally provides the strongest enforcement position because infringement can arise from making, using, selling, offering for sale, or importing the claimed compound under 35 U.S.C. § 271.[3]
The claim is not a broad genus covering all third-generation EGFR inhibitors. It identifies one specific molecular structure. Its breadth comes from the phrase “or a pharmaceutically acceptable salt thereof,” which extends the claim beyond the neutral free base to qualifying salt forms.
Commercial significance of claim 1
Claim 1 can reach:
- Osimertinib free base;
- Osimertinib mesylate;
- Other pharmaceutically acceptable osimertinib salts, depending on claim construction and proof of salt identity;
- Drug substances imported into the United States;
- Drug products made from the claimed compound.
A generic applicant cannot avoid claim 1 merely by using a different tablet excipient or manufacturing site if the finished drug substance remains the claimed compound or salt.
What does claim 7 protect?
Claim 7 specifically protects the mesylate salt of osimertinib. This is the claim most directly aligned with the active ingredient in Tagrisso tablets.
The supplied text contains an apparent transcription error in the chemical name, referring to “1-methylindol-3-yppyrimidin-2-yl.” The corresponding structure is understood from the remaining claims and the known osimertinib chemical identity to be the 4-(1-methylindol-3-yl)pyrimidin-2-yl group. The legal effect of the typographical defect would depend on the issued patent record, specification, prosecution history, and claim-construction principles. The issued patent and regulatory records should control over an OCR or transcription version of the claim.[1][4]
Claim 7 is narrower than claim 1 because it is limited to the mesylate salt. It is commercially significant because a generic product using osimertinib mesylate would ordinarily practice both the broader salt claim and the specific mesylate claim.
What formulations are protected by US 8,946,235?
Claims 2, 5, and 8 protect pharmaceutical compositions containing the claimed molecular form with a pharmaceutically acceptable diluent or carrier.
These claims are broad at the composition level but do not recite:
- A specific tablet design;
- A particular excipient;
- A dissolution profile;
- A dosage strength;
- A coating;
- A release mechanism;
- A particle-size distribution;
- A manufacturing process.
The claims can therefore cover ordinary oral dosage forms containing the claimed compound, including tablets or other pharmaceutical compositions, provided the composition contains the claimed drug substance and a pharmaceutically acceptable carrier.
The formulation claims should be distinguished from later or separate patents that may protect specific tablet compositions, stability systems, particle properties, solid-state forms, or manufacturing processes. A generic applicant may avoid a narrow formulation patent while still infringing the core compound or mesylate claim.
What lung-cancer methods are protected?
Claims 3, 6, and 9 cover administering osimertinib, the free base, or the mesylate salt to treat lung cancer in a warm-blooded animal. Claims 10 through 12 narrow those methods to NSCLC.
The claims do not expressly require:
- An EGFR mutation;
- The T790M resistance mutation;
- Exon 19 deletion;
- L858R mutation;
- A specific treatment line;
- A particular dose;
- Combination therapy;
- Metastatic disease;
- Adjuvant therapy;
- A specified duration of treatment.
The absence of these limitations makes the method claims potentially broad within the lung-cancer field. Their practical enforceability depends on the approved indication, prescribing behavior, product labeling, induced-infringement evidence, and the validity of the underlying compound claims.
Method-claim limitations
| Claim |
Required therapeutic subject matter |
| 3 |
Osimertinib or pharmaceutically acceptable salt for lung cancer |
| 6 |
Osimertinib free base for lung cancer |
| 9 |
Osimertinib mesylate for lung cancer |
| 10 |
Claim 3 limited to NSCLC |
| 11 |
Claim 6 limited to NSCLC |
| 12 |
Claim 9 limited to NSCLC |
The method claims are not limited to treating only T790M-positive tumors. FDA-approved use has expanded over time, but the patent claim language itself should be analyzed separately from the current label.[2]
When does US Patent 8,946,235 expire?
The patent has a standard statutory term calculated from the relevant US application or PCT filing framework. Public patent records identify an April 20, 2032 base expiration date for the patent family, subject to any applicable patent-term adjustment, patent-term extension, terminal disclaimer, or other statutory modification.[1][5]
| Milestone |
Date or status |
| Earliest reported priority |
April 20, 2012 |
| US patent grant |
February 3, 2015 |
| Base patent expiration commonly reported |
April 20, 2032 |
| Patent-term adjustment or extension |
Must be verified against the USPTO patent record and Orange Book listing |
| FDA New Chemical Entity exclusivity |
Expired in 2020 |
| Current commercial relevance |
Core compound protection remains the principal barrier until patent expiry or successful challenge |
The base patent date should not be treated as the complete US exclusivity endpoint. FDA Orange Book listings may include separate patents with later expiration dates, and an approved product can receive patent-term extension under 35 U.S.C. § 156 if statutory requirements are met.[5][6]
What is the FDA regulatory status of Tagrisso?
FDA approved Tagrisso, osimertinib mesylate, in November 2015 for previously treated metastatic EGFR T790M mutation-positive NSCLC under an accelerated approval pathway.[2]
The FDA later expanded the label to include broader EGFR-mutated NSCLC populations and additional treatment settings. Key regulatory developments include:
| FDA milestone |
Significance |
| November 2015 |
Initial approval for metastatic EGFR T790M-positive NSCLC after prior EGFR therapy |
| March 2017 |
Regular approval for metastatic EGFR T790M-positive NSCLC |
| December 2017 |
First-line treatment for metastatic NSCLC with specified EGFR mutations |
| December 2020 |
Adjuvant treatment after tumor resection for EGFR-mutated NSCLC |
| Later label expansion |
Additional locally advanced or unresectable EGFR-mutated NSCLC use, subject to the current FDA label |
The regulatory indication is relevant to method-of-use patents and induced-infringement analysis. It does not eliminate the separate risk created by claims 1 and 7, which are directed to the drug substance itself.
What is the Orange Book status of osimertinib?
Tagrisso is listed in the FDA Orange Book as a prescription drug product with patent information submitted by AstraZeneca.[6] The principal Orange Book risk categories are:
- Core compound or salt patents;
- Formulation patents;
- Method-of-use patents;
- Later patents covering additional clinical uses or product characteristics.
For generic entry, the most important listed patent is the one that covers osimertinib or osimertinib mesylate as a product. A generic applicant relying on an abbreviated new drug application (ANDA) generally must address each listed patent through a Paragraph I, II, III, or IV certification, as applicable.[7]
The Orange Book status must be checked against the current FDA listing because patent listings, use codes, expiration dates, and regulatory exclusivity can change. A historical review of US 8,946,235 alone is not sufficient to identify every currently listed Tagrisso patent.
What Paragraph IV challenges affect osimertinib?
A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or not infringed. For osimertinib, the core commercial question is whether a generic applicant can challenge the compound or mesylate patent while avoiding later formulation and method-of-use patents.
A Paragraph IV case involving the core compound could seek:
- A declaration that the compound claim is invalid;
- A declaration that the generic product does not infringe;
- A judgment that the patent is unenforceable;
- Market entry before the listed patent’s expiration.
A first-filed substantially complete Paragraph IV ANDA may qualify for 180-day generic exclusivity under the Hatch-Waxman framework, subject to statutory forfeiture provisions.[7]
The principal invalidity theories for a compound patent of this type could include:
- Lack of novelty;
- Obviousness;
- Written-description failure;
- Enablement;
- Indefiniteness;
- Double patenting;
- Inequitable conduct, if supported by the record.
The compound claim is generally harder to design around than a method claim. A challenger that uses the same active moiety in a different salt, tablet, or manufacturing process remains exposed to claims 1 and 7.
Which companies are challenging Tagrisso exclusivity?
Publicly reportable challengers must be identified through the current Orange Book, Paragraph IV notices, ANDA litigation dockets, and district-court filings. The supplied claim text does not identify a challenger, ANDA filer, case number, or settlement agreement.
No reliable current litigation conclusion can be drawn from US Patent 8,946,235 alone. A litigation search must distinguish:
- Challenges to US 8,946,235;
- Challenges to later Tagrisso patents;
- Declaratory-judgment actions;
- ANDA cases filed under 21 U.S.C. § 355(j);
- Patent disputes concerning other AstraZeneca products;
- Foreign oppositions or revocation actions.
The absence of a named challenger in the supplied material means the patent’s litigation status is not established by the claim set.
What patent landscape surrounds osimertinib?
The osimertinib estate is broader than US 8,946,235. A commercial freedom-to-operate review should map at least five patent layers.
Core molecule patents
These protect osimertinib itself, its salts, and potentially stereochemical or crystalline forms. US 8,946,235 is in this category.
Formulation patents
These may cover:
- Specific tablet compositions;
- Excipients;
- Stability-enhancing systems;
- Granulation or coating processes;
- Dissolution characteristics;
- Solid-state forms.
A formulation patent can remain relevant even after a core compound patent expires, although its practical value depends on whether a generic can use a non-infringing formulation.
Method-of-use patents
These may cover:
- EGFR-mutated NSCLC;
- T790M-positive disease;
- First-line therapy;
- Adjuvant therapy;
- Unresectable stage III disease;
- Combination treatment;
- Specific sequencing after prior EGFR inhibitors.
Method patents are more vulnerable to skinny-label strategies than composition-of-matter claims, but a generic’s label and promotional conduct must be structured carefully.
Manufacturing patents
Manufacturing patents may cover intermediates, coupling reactions, purification, salt formation, crystallization, or process conditions. These patents can affect API sourcing even when a finished-product patent does not apply.
Geographic patent families
AstraZeneca’s osimertinib portfolio includes corresponding patent filings in major pharmaceutical markets, including Europe, Japan, China, Canada, Australia, and other jurisdictions. Expiration, opposition outcomes, supplementary protection certificates, patent-term adjustments, and regulatory exclusivities differ by country.
US 8,946,235 has no automatic legal effect outside the United States. Foreign entry analysis requires a country-specific family review.
How strong is the patent estate for osimertinib?
The core estate is commercially strong because the patent claims directly recite the active molecule and the marketed mesylate salt. A generic applicant cannot readily avoid those claims through:
- A different tablet excipient;
- A different manufacturing location;
- A different dosage strength;
- A different supplier;
- A different therapeutic label, if the product itself remains the claimed compound.
The method claims are less central to basic product entry because the compound claims independently create infringement risk. Their value increases when later patents cover new indications or when a generic relies on a restricted label.
Relative strength by claim type
| Claim type |
Relative strength |
Main vulnerability |
| Claim 1 compound/salt |
High |
Prior art, obviousness, enablement, claim construction |
| Claim 4 free base |
High |
Duplication and scope overlap with claim 1 |
| Claim 7 mesylate |
High for marketed product |
Salt-specific validity and written-description issues |
| Claims 2, 5, 8 compositions |
Moderate to high |
Non-infringing formulation design |
| Claims 3, 6, 9 treatment |
Moderate |
Label, prescribing, divided infringement, statutory method defenses |
| Claims 10-12 NSCLC |
Moderate |
Narrower disease limitation and regulatory-label strategy |
What generic launch scenarios exist for Tagrisso?
Four launch scenarios are commercially relevant.
Launch after patent expiry
This is the lowest-litigation-risk scenario. The generic applicant waits until expiration of the core compound and mesylate claims, then launches subject to any surviving formulation or method patents.
Launch after a successful Paragraph IV challenge
A successful invalidity or non-infringement judgment could permit earlier entry. The commercial value would depend on whether later Orange Book-listed patents remain enforceable.
At-risk launch
A generic company may launch before final resolution of all patent litigation. This exposes the company to damages, possible injunction risk, and substantial financial liability if the patent is upheld.
Skinny-label launch
A generic may omit patented indications from its label where FDA and Hatch-Waxman requirements permit. This strategy is more relevant to method-of-use patents than to claims 1 and 7. It does not avoid infringement of a valid compound or mesylate claim.
What revenue exposure is associated with osimertinib patents?
Tagrisso is one of AstraZeneca’s major oncology products. The patent estate protects a product with material revenue exposure across metastatic, adjuvant, and locally advanced NSCLC indications.
Revenue risk is concentrated around the first legally available generic entry date. A generic launch could affect:
- US product revenue;
- Net price and rebate levels;
- International reference pricing;
- Hospital and specialty-pharmacy purchasing;
- AstraZeneca’s oncology portfolio valuation;
- Licensing and settlement economics.
The precise revenue exposure requires current AstraZeneca annual-report figures and a defined reporting period. The supplied patent information does not establish a current revenue amount.
Do biosimilar rules apply to osimertinib?
No. Osimertinib is a small-molecule drug, not a biologic. Biosimilar approval under the Biologics Price Competition and Innovation Act does not apply.
The relevant US competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Generic applicants must establish pharmaceutical equivalence and bioequivalence to the reference-listed drug, subject to applicable patent certifications and regulatory exclusivities.[7]
The competitive risks are therefore generic-entry risks, not biosimilar-substitution risks.
What licensing or settlement agreements affect osimertinib?
AstraZeneca has entered into numerous oncology collaborations across its portfolio, but the supplied patent record does not establish a specific license, covenant not to sue, or settlement agreement relating to US 8,946,235.
A valid transaction analysis should separate:
- License agreements for osimertinib development or commercialization;
- Regional commercialization agreements;
- Patent settlements with ANDA applicants;
- Supply agreements;
- Co-development arrangements;
- Royalty-bearing intellectual-property licenses.
Without an identified agreement or docket, no settlement term, authorized-generic provision, launch date, royalty, or licensee should be attributed to this patent.
Key Takeaways
- US 8,946,235 is a core osimertinib patent assigned to AstraZeneca.
- Claim 1 covers osimertinib and pharmaceutically acceptable salts.
- Claim 4 separately claims the free base.
- Claim 7 specifically claims osimertinib mesylate, the active ingredient used in Tagrisso.
- Claims 2, 5, and 8 cover pharmaceutical compositions.
- Claims 3, 6, and 9 cover lung-cancer treatment; claims 10 through 12 narrow the methods to NSCLC.
- The commonly reported base expiration date is April 20, 2032, subject to verified patent-term adjustments, extensions, and Orange Book data.
- Osimertinib is regulated through the generic ANDA pathway, not the biosimilar pathway.
- The core compound and mesylate claims create the principal generic-entry barrier.
- Formulation, method-of-use, manufacturing, and later indication patents may extend or complicate the commercial exclusivity analysis.
- A current Paragraph IV and litigation conclusion cannot be drawn from the claim text alone.
FAQs About US Patent 8,946,235 and Tagrisso
Is US Patent 8,946,235 a composition-of-matter patent?
Yes. Claims 1, 4, and 7 directly claim osimertinib, its free base, and its mesylate salt. These are composition-of-matter claims.
Does changing osimertinib mesylate to another salt avoid the patent?
Not necessarily. Claim 1 covers osimertinib and pharmaceutically acceptable salts broadly. A different salt could still fall within claim 1 even if it does not fall within the mesylate-specific claim 7.
Does US 8,946,235 cover osimertinib for leukemia or other cancers?
The compound claims are not limited to lung cancer. The method claims supplied here are limited to lung cancer, with narrower claims for NSCLC. Use in another cancer may still implicate the compound and composition claims.
Can a generic launch with a different tablet formulation avoid this patent?
No, not necessarily. A different formulation may avoid a formulation-specific patent, but it would not avoid a valid compound or mesylate claim if the generic product contains osimertinib or osimertinib mesylate.
Is Tagrisso protected by a biosimilar exclusivity period?
No. Tagrisso contains the small-molecule drug osimertinib mesylate. Generic competition proceeds through the ANDA pathway rather than the biosimilar pathway.
References
- United States Patent and Trademark Office. (2015). US Patent No. 8,946,235, N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide.
- U.S. Food and Drug Administration. (2024). Tagrisso prescribing information: Osimertinib tablets. AstraZeneca Pharmaceuticals LP.
- 35 U.S.C. § 271. Infringement of patents.
- 35 U.S.C. § 112. Specification requirements.
- 35 U.S.C. §§ 154, 156. Patent term and patent-term extension.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j). Abbreviated new drug applications.
