US Patent 10,610,125: Scope, Claims, Expiration and IDH Inhibitor Patent Landscape
US Patent No. 10,610,125 is a broad method-of-treatment patent directed to acute myelogenous leukemia, or AML, harboring oncogenic IDH1 or IDH2 mutations. Its claims cover treating mutation-positive AML with a small-molecule mutant-IDH inhibitor and include diagnostic-selection limitations based on detecting the relevant mutation.
The patent is strategically important because it is not limited to one chemical structure. It reaches approved and investigational IDH inhibitors through functional and disease-use language. Its principal commercial relevance is to ivosidenib, marketed as Tibsovo for mutant-IDH1 AML, and enasidenib, marketed as Idhifa for mutant-IDH2 AML. It may also be relevant to other small-molecule inhibitors if they are used to treat AML with the claimed mutations.
What does US Patent 10,610,125 cover?
The patent claims a treatment sequence with four core elements:
- The patient has AML.
- The AML contains a mutant IDH1 or IDH2 enzyme capable of converting alpha-ketoglutarate to 2-hydroxyglutarate, or 2HG.
- The patient receives a therapeutically effective amount of a small-molecule inhibitor of that mutant enzyme.
- In dependent claims, the mutation may be detected in tissue or bodily fluid, including by PCR-based sequencing.
The independent claim is materially broader than a claim limited to ivosidenib, enasidenib, or another named chemical compound.
Claim architecture
| Claim |
Principal limitation |
Commercial significance |
| 1 |
Treating mutant-IDH1 or mutant-IDH2 AML with a small-molecule inhibitor |
Broad genus claim covering the therapeutic concept |
| 2 |
Inhibitor binds IDH1R132X or IDH2R172X and blocks 2HG production |
Links treatment to the principal oncogenic mutation classes |
| 3 |
AML characterized by an IDH1 mutation |
Covers IDH1-directed AML treatment |
| 4 |
IDH1R132X mutation |
Covers the arginine-132 mutation family |
| 5 |
R132H, R132C, R132S, R132G, R132L or R132V |
Enumerates common IDH1 variants |
| 6 |
AML characterized by an IDH2 mutation |
Covers IDH2-directed AML treatment |
| 7 |
IDH2R172X mutation |
Covers the principal IDH2 mutation family; the supplied text identifies this as “IDH1R172X,” which appears inconsistent with claim 6 |
| 8 |
R172K, R172M, R172S, R172G or R172W |
Enumerates common IDH2 variants |
| 9 |
Mutation detected in a patient sample |
Adds a biomarker-selection requirement |
| 10 |
Tissue or bodily fluid sample |
Broadens the sample sources |
| 11 |
Sequencing nucleic acid from an affected cell |
Covers molecular confirmation of the mutation |
| 12 |
PCR-based sequencing |
Adds a specific diagnostic technique |
How broad is the independent treatment claim?
Claim 1 is a functional method claim. It does not require a particular chemical structure, dosage, formulation, route of administration, treatment line, or response threshold.
A claimant would generally need to establish:
- The treated disease is AML.
- The AML contains a qualifying mutant IDH1 or IDH2 enzyme.
- The mutation gives the enzyme the ability to produce 2HG from alpha-ketoglutarate.
- The administered agent is a small-molecule inhibitor of the relevant mutant enzyme.
- The amount administered is therapeutically effective.
The claim does not expressly require:
- Relapsed or refractory AML.
- Newly diagnosed AML.
- Monotherapy.
- A particular dose or dosing schedule.
- Complete remission or another clinical response.
- A specific diagnostic assay.
- A named inhibitor.
- A particular IDH1 or IDH2 mutation in the independent claim.
This structure gives the patent potentially broad reach against products used in mutation-selected AML, even if the product itself is chemically different from the compounds disclosed in the patent family.
Functional claiming creates both strength and litigation risk
The claim’s breadth is commercially useful but legally exposed. A patent challenger could focus on:
- Written description and enablement across the full IDH1/IDH2 inhibitor genus.
- Whether the specification supports every claimed mutation and inhibitor class.
- The meaning of “small molecule inhibitor.”
- Whether the accused compound inhibits mutant IDH1 or IDH2 in the claimed manner.
- Whether a particular patient population has the claimed mutation.
- Whether a product label or actual use establishes a therapeutically effective amount.
A product containing a compound that inhibits only wild-type IDH, or that acts through a mechanism unrelated to blocking mutant IDH-mediated 2HG production, would present a weaker infringement case under claim 1.
Which IDH1 and IDH2 mutations are covered?
The claims distinguish the two principal mutation groups:
| Enzyme |
Mutation class |
Listed variants |
| IDH1 |
R132X |
R132H, R132C, R132S, R132G, R132L and R132V |
| IDH2 |
R172X |
R172K, R172M, R172S, R172G and R172W |
IDH1 R132H and R132C are especially relevant to ivosidenib development and clinical testing. IDH2 R172K is a principal mutation addressed by enasidenib.
The claims are not limited to one specific mutation when the broader R132X or R172X language applies. The enumerated dependent claims provide more specific fallback positions if the broader mutation-class claims are narrowed or challenged.
The supplied version of claim 7 states “IDH1R172X” even though claims 6 and 8 concern IDH2. The relevant biological and claim context indicates that IDH2R172X is the intended limitation. The issued patent text and prosecution history control for enforcement analysis.
Does the patent cover ivosidenib and enasidenib?
Ivosidenib
Ivosidenib is a small-molecule inhibitor of mutant IDH1. The FDA approved Tibsovo for:
- Adults with relapsed or refractory AML with a susceptible IDH1 mutation.
- Adults aged 75 years or older, or adults with comorbidities precluding intensive induction chemotherapy, with newly diagnosed AML containing a susceptible IDH1 mutation.
- Other IDH1-mutated malignancies under subsequent regulatory expansions.
Use of ivosidenib for IDH1-mutated AML is closely aligned with claims 1, 3, 4, 5 and, where mutation testing is performed, claims 9 through 12. The patent therefore has direct method-of-use relevance to Tibsovo’s AML indications. FDA labeling requires identification of a susceptible IDH1 mutation using an FDA-approved test or another validated method, which also supports the diagnostic limitations in the dependent claims.[2]
Enasidenib
Enasidenib is a small-molecule inhibitor of mutant IDH2. Idhifa received FDA approval for adults with relapsed or refractory AML with an IDH2 mutation.
Its use aligns with claims 1, 2, 6, 7 and 8. Claims 9 through 12 may apply when IDH2 status is confirmed through sequencing or another molecular assay.
The patent does not require the inhibitor to be selective for IDH1 rather than IDH2. It covers both enzyme classes in the alternative. That dual-enzyme structure increases potential coverage but also creates a broader enablement and written-description perimeter than a patent limited to one compound or one enzyme.
What are the patent expiration and exclusivity timelines?
US Patent 10,610,125 issued on April 7, 2020. Public patent records associate the patent with the Agios mutant-IDH research portfolio. Its ordinary patent term is expected to run into the early 2030s, subject to the patent family’s priority chain, patent-term adjustment, terminal disclaimers and any applicable patent-term extension.
The patent term should not be confused with FDA regulatory exclusivity.
| Protection type |
Relevance |
| US Patent 10,610,125 |
Method-of-treatment protection for mutant-IDH AML |
| Orange Book listing |
Depends on whether FDA lists the patent against a specific approved product and indication |
| New chemical entity exclusivity |
Applies to the approved active ingredient, not automatically to every method patent |
| Orphan-drug exclusivity |
May block approval of the same drug for the same orphan indication during the exclusivity period |
| Pediatric exclusivity |
Can add six months to qualifying FDA exclusivity and patent periods |
| Patent-term extension |
Product-specific and limited to statutory eligibility requirements |
FDA regulatory exclusivity for ivosidenib and enasidenib does not eliminate the significance of the patent. After regulatory exclusivity expires, an ANDA or 505(b)(2) applicant may still face patent-based barriers.
The operative expiration date should be determined from the USPTO patent record, including the patent-term-adjustment calculation and the complete continuation and terminal-disclaimer history.[1]
What is the Orange Book status of the patent?
A method-of-treatment patent can be listed in the FDA Orange Book if it claims an approved method of using the drug. Listing does not establish validity or infringement. It gives the patent a procedural role in the ANDA pathway.
For a listed patent, an ANDA applicant may submit:
- Paragraph I certification: no patent information is listed.
- Paragraph II certification: the patent has expired.
- Paragraph III certification: approval is sought after expiration.
- Paragraph IV certification: the patent is invalid, unenforceable or will not be infringed.
- A section viii statement: the applicant will carve out a patented method of use, where FDA permits the carve-out.
For ivosidenib and enasidenib, the commercial impact depends on whether the relevant FDA-approved AML use is protected by this patent, another compound patent, a formulation patent or a separate method patent. Patent listings must be evaluated product by product through the current Orange Book and FDA patent submission records.[3]
What Paragraph IV challenges and generic-entry risks exist?
A generic applicant targeting ivosidenib or enasidenib could challenge this patent through a Paragraph IV certification if the patent is listed against the reference product.
The principal challenge theories would be:
Non-infringement
An applicant could argue that its proposed label does not direct use in mutant-IDH AML, or that it omits the protected indication under a valid section viii carve-out.
This strategy is difficult if the product has no meaningful non-infringing use and the FDA-approved label retains mutant-IDH AML treatment.
Invalidity
Potential invalidity arguments include:
- Lack of enablement across all small-molecule inhibitors of mutant IDH1 and IDH2.
- Lack of written description for the full functional genus.
- Anticipation by earlier mutant-IDH treatment disclosures.
- Obviousness based on IDH mutation biology, 2HG inhibition and prior small-molecule inhibitor disclosures.
- Indefiniteness involving “therapeutically effective amount,” “small molecule inhibitor” or the functional 2HG limitation.
Label-based infringement
A skinny label can reduce risk only if the patented method can be removed without encouraging the protected use. If the reference product is primarily approved for mutant-IDH AML, a carve-out may be commercially and regulatory difficult.
A first substantially complete Paragraph IV challenge may trigger a 30-month stay under the Hatch-Waxman Act, subject to statutory conditions and litigation timing.[4]
Does the patent cover formulations or manufacturing?
The supplied claims do not claim:
- A tablet, capsule or injectable formulation.
- A specific salt, polymorph or crystalline form.
- Particle size or excipient composition.
- A sustained-release or modified-release delivery system.
- A manufacturing process.
- A synthetic intermediate.
- A purification method.
The patent is therefore a use patent, not a conventional formulation or process patent.
A generic entrant could still face separate patents covering:
- The active pharmaceutical ingredient.
- Solid-state forms.
- Pharmaceutical compositions.
- Dosage regimens.
- Combination therapy.
- Manufacturing processes.
- Diagnostic testing or companion-diagnostic systems.
Those patents must be analyzed separately from US Patent 10,610,125. A challenge to this method patent would not necessarily clear the entire product patent estate.
How does the patent compare with the broader IDH inhibitor landscape?
Ivosidenib versus enasidenib
| Attribute |
Ivosidenib |
Enasidenib |
| Target |
Mutant IDH1 |
Mutant IDH2 |
| Key AML mutations |
IDH1 R132 variants |
IDH2 R140 and R172 variants |
| FDA AML approval |
2018, expanded to newly diagnosed AML in 2022 |
2017 for relapsed or refractory AML |
| Brand |
Tibsovo |
Idhifa |
| Relevance to US 10,610,125 |
Claims 1-5 and 9-12 |
Claims 1, 2 and 6-12 |
| Main regulatory pathway |
NDA |
NDA |
| Biosimilar risk |
None in the conventional biologic sense |
None in the conventional biologic sense |
| Generic risk |
ANDA or 505(b)(2), depending on product |
ANDA or 505(b)(2), depending on product |
The patent is more important for use protection than for molecule exclusivity. A competitor could potentially develop a chemically distinct inhibitor and still encounter the claims if it is used for mutation-positive AML.
Olutasidenib and other IDH inhibitors
Olutasidenib, an oral mutant-IDH1 inhibitor marketed as Rezlidhia, received FDA approval for relapsed or refractory AML with a susceptible IDH1 mutation. Its product-specific patent estate is separate from the patent estate for ivosidenib, but its use in the same disease and mutation category creates potential overlap with broad mutant-IDH AML method claims.
Vorasidenib is a dual mutant-IDH1/IDH2 inhibitor approved for grade 2 astrocytoma with susceptible IDH1 or IDH2 mutations. Its principal indication is a different cancer type. Use of vorasidenib for AML could implicate the broad disease-and-mechanism language in US 10,610,125 if the other claim elements are satisfied, although its approved label does not establish AML use.[5]
What licensing deals affect the patent?
Agios Pharmaceuticals developed the mutant-IDH platform and associated patent portfolio. Servier obtained rights to commercialize mutant-IDH products through transactions and collaboration arrangements involving Agios. The commercial rights to Tibsovo and Idhifa have been affected by those arrangements and subsequent portfolio transactions.
Patent ownership, exclusive licensing, royalty rights and enforcement authority must be distinguished. The entity commercializing a product is not necessarily the sole owner of every patent covering the product or its use. For litigation and licensing analysis, the current assignment record and operative license agreements are controlling.
How strong is the patent estate?
US Patent 10,610,125 is strongest against:
- Use of an IDH1 or IDH2 inhibitor in AML.
- Labels that expressly require or recommend mutation testing.
- Products with no substantial non-infringing AML use.
- Competitors entering before the relevant patent term ends.
- Products whose labels identify the same mutation classes listed in claims 4, 5, 7 and 8.
Its relative weaknesses are:
- It is not limited to a specific compound.
- Broad functional claims can face enablement and written-description attacks.
- It does not independently block manufacture or sale of an inhibitor.
- It may be avoidable through an approved label that omits the protected AML use, if FDA permits the carve-out.
- Separate compound and formulation patents may be more important to generic entry than this method patent.
The estate should be assessed as a layered portfolio rather than as a single patent. Compound claims usually provide the strongest direct barrier to generic manufacture. Method claims provide important supplemental protection when the product’s principal use is the patented indication.
What generic launch scenarios exist?
| Scenario |
Likely exposure |
| Generic launches with the same mutant-IDH AML indication |
High method-patent and product-patent risk |
| Generic uses a section viii carve-out |
Depends on whether non-infringing use is commercially viable |
| 505(b)(2) product with a different indication |
Lower direct method risk, but formulation and clinical-use patents remain relevant |
| New chemically distinct IDH inhibitor |
Potential method-claim exposure if used in AML |
| Non-IDH-directed AML therapy |
Outside the core claims |
| Inhibitor used without mutation selection |
May avoid claims requiring detection, but not necessarily claim 1 |
Key Takeaways
- US Patent 10,610,125 is a broad mutant-IDH AML treatment patent.
- The independent claim covers small-molecule inhibition of mutant IDH1 or IDH2 without naming a specific compound.
- Ivosidenib is the principal IDH1 product aligned with the patent; enasidenib is the principal IDH2 product.
- The patent also has potential relevance to olutasidenib and other mutant-IDH inhibitors used for AML.
- Claims 9 through 12 add mutation-detection and sequencing limitations, but claims 1 through 8 do not require a particular diagnostic method.
- The patent does not claim formulations, crystalline forms, manufacturing processes or a specific chemical structure.
- Generic risk depends on the full Orange Book listing, compound patents, method patents and any permitted label carve-out.
- The patent issued on April 7, 2020, with ordinary patent protection expected to extend into the early 2030s, subject to USPTO term calculations.
- The supplied text’s reference to “IDH1R172X” in claim 7 is inconsistent with the surrounding IDH2 claims and should be checked against the issued patent.
FAQs
Does US Patent 10,610,125 cover all IDH inhibitors?
No. It covers small-molecule inhibitors used to treat AML containing qualifying mutant IDH1 or IDH2 enzymes. An inhibitor used for another disease or without the required mutant-IDH biology may fall outside the claims.
Is ivosidenib directly implicated by this patent?
Yes. Ivosidenib is a mutant-IDH1 inhibitor, and its use in IDH1-mutated AML maps closely to the patent’s treatment claims.
Is enasidenib directly implicated by this patent?
Yes. Enasidenib inhibits mutant IDH2 and its use in IDH2-mutated AML maps closely to the IDH2 limitations.
Can a generic avoid the patent by omitting mutation testing?
Not necessarily. Claims 9 through 12 require detection or sequencing, but the broader treatment claims do not expressly require a particular diagnostic procedure.
Does the patent create biosimilar risk?
No conventional biosimilar pathway applies because ivosidenib, enasidenib and olutasidenib are small-molecule drugs. The relevant competition pathways are generally ANDA or 505(b)(2) applications.
References
- United States Patent and Trademark Office. (2020). U.S. Patent No. 10,610,125.
- U.S. Food and Drug Administration. (2024). Tibsovo (ivosidenib) prescribing information.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- U.S. Food and Drug Administration. (2015). Guidance for industry: 180-day exclusivity: Questions and answers.
- U.S. Food and Drug Administration. (2024). Voranigo (vorasidenib) prescribing information.
