US Patent 10,414,752: Claim Scope, Vorasidenib Protection, and Generic Entry Risk

US Patent 10,414,752 protects pharmaceutical compositions containing highly enantiomerically pure vorasidenib, the mutant IDH1 inhibitor marketed as Voranigo. Its strongest commercial claims cover solid oral formulations containing at least 98% enantiomeric excess of the active S-enantiomer, including compositions containing about 50 mg to 150 mg of drug. The patent also reaches residual synthetic intermediates and compositions made through specified coupling reactions.

The patent is commercially relevant because vorasidenib is the active ingredient in Voranigo, which the FDA approved in August 2024 for certain patients with grade 2 astrocytoma or oligodendroglioma carrying susceptible IDH1 or IDH2 mutations. The patent’s estimated ordinary expiration is in 2035, subject to any patent-term adjustment or patent-term extension recorded by the USPTO.

What drug does US Patent 10,414,752 protect?

The claimed active compound is:

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile

This compound is vorasidenib, also known as AG-881. Vorasidenib is an oral small-molecule inhibitor of mutant IDH1 and IDH2 enzymes. The patent does not claim every IDH inhibitor. It claims a specific stereochemically defined compound and compositions containing that compound.

The chemical identity matters because the claims are directed to the S-enantiomer. A composition containing the corresponding R-enantiomer, a racemate, or another IDH inhibitor would not fall within the claims merely because it has the same therapeutic use.

Core patent data

Item	Data
US patent	10,414,752
Patent title	Pharmaceutical compositions comprising an IDH1 inhibitor
Patent owner/assignee	Agios Pharmaceuticals, Inc.
Patent type	Composition, pharmaceutical formulation, and product-by-process claims
Grant date	September 17, 2019
Active pharmaceutical ingredient	Vorasidenib, AG-881
Enantiomeric purity threshold	At least 98% ee by chiral HPLC
Principal dosage range	About 50 mg to 150 mg in claims 13, 14, and 20
Estimated base expiration	Approximately March 2035
FDA product	Voranigo
FDA approval date	August 6, 2024

The priority and prosecution history should be reviewed directly in the USPTO Patent Center before relying on the estimated expiration date for litigation or transaction purposes. The ordinary term is generally calculated from the earliest effective nonprovisional or international application filing date, not from the grant date.

How are claims 1 through 8 structured?

Claims 1 through 8 cover compositions containing vorasidenib and, in some cases, specified synthetic intermediates.

Claim 1: high-purity vorasidenib composition

Claim 1 requires:

A composition;
A compound of Formula I-13; and
At least 98% enantiomeric excess, measured by chiral HPLC.

Formula I-13 is the S-enantiomer of vorasidenib. The claim is not limited to a pharmaceutical dosage form. It can potentially cover an active pharmaceutical ingredient composition, an intermediate formulation, a manufacturing mixture, or another composition containing the required compound at the required stereochemical purity.

The claim does not recite a particular excipient, dosage strength, tablet architecture, polymorph, particle size, or manufacturing process. Its central limitations are chemical identity and enantiomeric purity.

A potential infringement issue would therefore focus on:

Whether the product contains Formula I-13;
Whether the product is at least 98% ee;
Whether the accused material is a composition rather than isolated compound language outside the claim scope; and
Whether the analytical method used to determine ee is comparable to the claimed chiral HPLC method.

Claims 2 to 4: residual intermediate combinations

Claims 2 to 4 add Formula III-1 and Formula II-1 to the composition.

These claims appear directed to compositions that contain vorasidenib together with one or more process intermediates. Such claims can capture reaction mixtures, crude product streams, partially purified material, or manufacturing batches before complete removal of starting materials and intermediates.

Claim 2 requires Formula III-1. Claim 3 requires Formula II-1. Claim 4 requires both Formula II-1 and Formula III-1 through dependency from claim 3.

Because the structural drawings for Formulas II-1 and III-1 are not included in the supplied claim text, their exact chemical identities cannot be independently mapped here. Their legal function is clear: they are starting materials or intermediates associated with the synthesis of Formula I-13.

Claim 5: product-by-process limitation

Claim 5 requires that Formula I-13 be obtained by reacting Formula II-1 with Formula III-1.

This is a product-by-process formulation. The claim remains directed to a composition containing the specified product, but it adds a limitation concerning how the compound was obtained. The scope may depend on how a court interprets the process language under US product-by-process doctrine.

For enforcement, the patentee may face evidentiary issues if the accused manufacturer uses a different synthetic route. The critical question would be whether the process limitation narrows the claim to product made by the stated reaction or instead identifies a product that is structurally and stereochemically defined independently of the manufacturing route.

Claims 6 to 8: alternative synthetic route

Claims 6 to 8 add Formula V-2 and Formula IV-1. Claim 8 specifies that Formula I-13 is obtained by reacting Formula IV-1 with Formula V-2.

These claims protect a second manufacturing pathway. They may be useful against a manufacturer whose process does not use the Formula II-1/Formula III-1 route but does use the alternative pair of intermediates.

The two process branches create a layered manufacturing position:

Claim group	Required additional subject matter	Commercial relevance
Claim 1	≥98% ee Formula I-13	Broadest composition claim
Claims 2-4	Formula II-1 and/or Formula III-1	Crude or intermediate-containing compositions
Claim 5	Reaction of II-1 and III-1	First specified synthetic route
Claims 6-7	Formula V-2 and/or IV-1	Alternative intermediate composition
Claim 8	Reaction of IV-1 and V-2	Second specified synthetic route

What pharmaceutical formulations are protected?

Claims 9 through 20 move from general compositions to pharmaceutical products.

Claim 9: pharmaceutical composition

Claim 9 requires:

A pharmaceutical composition;
A pharmaceutically acceptable carrier; and
A mutant IDH1 inhibitor consisting of Formula I-13 at at least 98% ee.

The phrase "consisting of" applies to the mutant IDH1 inhibitor limitation. It excludes substitution of another mutant IDH1 inhibitor for Formula I-13 within the claimed active-inhibitor element. The overall pharmaceutical composition remains open because the claim begins with "comprising."

The claim can therefore cover a formulation containing high-purity vorasidenib with conventional excipients, including fillers, binders, disintegrants, lubricants, coatings, and other pharmaceutically acceptable materials.

Claims 10 to 12: oral solid dosage forms

These claims narrow the composition to:

Oral administration;
A solid dosage form; and
A tablet or capsule.

The claims do not require a specific release profile. They do not expressly require immediate release, extended release, enteric coating, a particular excipient system, or a specific crystalline form.

A conventional immediate-release tablet or capsule containing the claimed high-purity vorasidenib could be within the apparent scope if the other limitations are met.

Claims 13 and 14: 50 mg and 150 mg strengths

Claim 13 recites about 50 mg of Formula I-13. Claim 14 recites about 150 mg.

These are formulation-strength claims. "About" introduces a range of permissible variation that would likely be assessed using ordinary claim-construction principles and the patent’s specification.

The claimed strengths do not correspond directly to the principal marketed Voranigo tablet strengths identified in FDA labeling, which are 10 mg and 40 mg tablets. The claims can still be relevant to commercial manufacturing because a 50 mg or 150 mg amount may be present in a multi-tablet regimen, development formulation, clinical formulation, or nonmarketed strength.

Claims 15 to 18: pharmaceutical compositions with intermediates

Claims 15 through 18 combine the pharmaceutical composition limitations with Formula II-1 and Formula III-1 or with the specified reaction process.

These claims are less likely to read on a finished, fully purified commercial tablet if manufacturing controls remove the intermediates below detectable or claim-relevant levels. They are more relevant to:

Bulk drug substance;
In-process pharmaceutical material;
Crude active-ingredient mixtures;
Manufacturing records and batch testing; and
Contract manufacturing operations.

The process claims may create supply-chain exposure even where the final dosage form does not contain the claimed intermediate.

What does claim 19 add to the patent estate?

Claim 19 covers a pharmaceutical composition containing:

A pharmaceutically acceptable carrier; and
About 5% to about 90% by weight of the named vorasidenib compound.

This is a concentration-based composition claim. It does not expressly require 98% ee in claim 19 itself. Claim 20 adds the 98% ee requirement, solid oral dosage form, and 50 mg to 150 mg amount.

The 5% to 90% weight range is broad enough to encompass many conventional solid formulations. It may also cover formulations with relatively high drug loading, provided the composition satisfies the pharmaceutical-composition and carrier limitations.

Practical difference between claims 9 and 19

Issue	Claim 9	Claim 19
Active ingredient	Formula I-13	Named vorasidenib compound
Purity	At least 98% ee	Not expressly required in claim 19
Carrier	Required	Required
Dosage form	Not limited	Not limited
Drug loading	Not specified	About 5%-90% by weight
Commercial focus	High-purity pharmaceutical product	Drug-loaded composition
Narrower dependent claim	Claims 10-18	Claim 20

Claim 19 may be particularly important against formulations that meet the drug-loading range but are challenged on whether they satisfy the precise purity limitation in claim 9.

When does US Patent 10,414,752 lose exclusivity?

The patent’s estimated base expiration is approximately March 2035, based on the underlying priority framework associated with the Agios vorasidenib patent family. The effective date should be confirmed through the USPTO patent record, including any patent-term adjustment, terminal disclaimer, reexamination certificate, or patent-term extension.

Voranigo also received FDA new chemical entity exclusivity. The FDA approved Voranigo on August 6, 2024. The standard five-year NCE period generally prevents an ANDA submission until four years after approval unless the ANDA includes a Paragraph IV certification. The five-year period would ordinarily run through August 2029, while Paragraph IV filing eligibility would generally begin in August 2028.

Exclusivity mechanism	Estimated timing
FDA approval	August 6, 2024
Earliest ordinary ANDA filing point	August 6, 2028
Ordinary NCE exclusivity end	August 6, 2029
Estimated patent expiration	Approximately March 2035
Potential regulatory pediatric extension	Could extend applicable exclusivity or patent term if granted

NCE exclusivity and patent term operate independently. A generic applicant could potentially file with a Paragraph IV certification after the four-year NCE bar, but commercial launch would remain subject to patent litigation, a 30-month stay, settlement terms, and any enforceable patent claims.

What is the Orange Book status of Voranigo and this patent?

Voranigo is an FDA-approved small-molecule drug, so Orange Book listing is legally relevant. Unlike biologic products, it follows the Hatch-Waxman framework rather than the biosimilar pathway.

The relevant Orange Book questions are:

Whether US 10,414,752 is listed against Voranigo;
Which approved uses are associated with the patent;
Whether the listing is identified as a drug-substance, drug-product, or method-of-use patent;
Whether the listed patent has been delisted or disclaimed; and
Whether later Agios patents are listed with different expiration dates.

The supplied claims are composition and formulation claims, not conventional treatment method claims. If listed, the patent would be most relevant to a generic applicant’s product and formulation certifications rather than to a use-code-only challenge.

The official FDA Orange Book should control the current listing status. Patent databases alone do not establish whether a patent is currently listed for a specific approved product.

What Paragraph IV challenges and litigation risks exist?

A generic applicant challenging Voranigo could attack the patent on several grounds:

Noninfringement. The proposed product may use a different salt, solid form, purity profile, manufacturing route, or dosage strength.
Invalidity for anticipation. Prior art could be asserted against the 98% ee composition, formulation, or drug-loading limitations.
Obviousness. The challenger may argue that isolating the S-enantiomer, formulating it with standard excipients, or selecting the claimed drug-loading range would have been routine.
Indefiniteness. Disputes could concern "about," "composition," "obtained by," and the chiral HPLC measurement.
Written description or enablement. The challenger could contest whether the specification supports the full composition and concentration ranges.
Product-by-process scope. Claims 5 and 8 may generate disputes over whether the claimed process limits the resulting composition.

A Paragraph IV filing would likely trigger patent litigation under the Hatch-Waxman Act if Agios or an applicable licensee sued within 45 days. The filing could impose an FDA approval stay of up to 30 months, subject to statutory exceptions and court action.

No biosimilar challenge is available because vorasidenib is a chemically synthesized small molecule, not a biologic subject to the Biologics Price Competition and Innovation Act.

How strong is the patent estate?

US 10,414,752 has moderate-to-strong commercial value but narrower technical scope than a basic compound patent.

Strengths

It identifies the active S-enantiomer of vorasidenib.
It requires a high-purity threshold that is likely present in commercial drug substance.
It covers pharmaceutical compositions and oral solid dosage forms.
It includes specific dosage amounts and broad drug-loading language.
It contains alternative process-route claims.
It can create exposure for both finished-product and manufacturing operations.

Limitations

It does not appear to be a broad genus claim covering all IDH1 inhibitors.
Several claims depend on chemical formulas whose exact structures determine practical reach.
Product-by-process limitations can complicate enforcement.
Claims 13 and 14 focus on 50 mg and 150 mg amounts, while current labeled Voranigo tablet strengths are 10 mg and 40 mg.
A generic could attempt design-around strategies using a different dosage configuration, formulation process, or manufacturing route.
The patent’s value depends materially on whether it is currently listed in the Orange Book and whether related patents separately protect the active compound, therapeutic use, or solid form.

What generic launch scenarios exist?

Scenario 1: Paragraph IV challenge after the four-year NCE bar

A generic could file an ANDA with a Paragraph IV certification beginning around August 2028. Litigation could delay approval or result in an agreed launch date before the estimated 2035 patent expiration.

Scenario 2: Paragraph III certification

If the generic accepts the patent, it could file a Paragraph III certification and wait for patent expiration. This would likely place launch around the effective patent expiration date, subject to FDA approval and other listed patents.

Scenario 3: formulation design-around

A challenger could avoid some claims by using:

A dosage amount outside 50 mg to 150 mg;
A formulation outside the claimed 5% to 90% drug-loading range;
A different excipient or dosage architecture;
A manufacturing route that avoids the claimed intermediate reaction; or
A product that does not contain the claimed intermediate residues.

Design-around does not avoid claim 1 or claim 9 if the final composition still contains at least 98% ee Formula I-13 and meets the remaining composition limitations.

Scenario 4: invalidity challenge

The strongest invalidity arguments would likely focus on obviousness of enantiomeric purification and routine oral formulation, supported by prior art showing vorasidenib, its stereochemistry, therapeutic activity, or conventional tablet formulations. The patentee would respond that the claimed purity, selected composition, and clinical performance were not predictable from the prior art.

What licensing and competitive issues matter?

Agios is the principal originator associated with vorasidenib. Commercial evaluation should examine:

Agios licensing or commercialization agreements covering Voranigo;
Any rights granted to regional partners;
Patent ownership changes or security interests;
Related patent families covering the active compound or therapeutic use;
Contract manufacturing arrangements;
Government price negotiations and market-access restrictions; and
Competing IDH inhibitors, including ivosidenib and enasidenib.

Vorasidenib competes primarily through central nervous system penetration and dual IDH1/IDH2 activity in diffuse glioma. Ivosidenib is an IDH1 inhibitor with approved oncology uses, while enasidenib targets mutant IDH2. Their patent estates are separate and should not be treated as substitutes for the vorasidenib analysis.

Key Takeaways

US 10,414,752 protects compositions containing high-purity S-vorasidenib.
The main commercial threshold is at least 98% ee measured by chiral HPLC.
Claims 9 through 12 cover pharmaceutical, oral, solid, tablet, and capsule forms.
Claims 13, 14, and 20 target formulations containing about 50 mg to 150 mg.
Claim 19 covers a broad 5% to 90% by-weight vorasidenib composition.
Claims 5 and 8 add manufacturing-route limitations involving specified intermediates.
The estimated base patent expiration is approximately March 2035.
Voranigo’s five-year NCE exclusivity began August 6, 2024, with ordinary Paragraph IV filing eligibility generally beginning in August 2028.
Biosimilar litigation does not apply because vorasidenib is a small molecule.
The patent is commercially meaningful but does not replace separate compound, method-of-use, solid-form, or manufacturing patents in the broader Agios estate.

FAQs About US Patent 10,414,752

Does US Patent 10,414,752 claim vorasidenib itself?

No. Based on the supplied claims, it primarily claims compositions containing the specified S-enantiomer of vorasidenib, along with pharmaceutical formulations and selected manufacturing compositions. A separate basic compound patent could provide broader direct protection.

Are Voranigo 10 mg and 40 mg tablets literally within claims 13 and 14?

Claims 13 and 14 recite about 50 mg and about 150 mg, respectively. A single 10 mg or 40 mg tablet would not ordinarily satisfy those exact amount limitations, although other claims, including claims 1, 9, 10, 11, 12, 19, and 20, may be relevant depending on the complete formulation and claim construction.

Can a generic avoid this patent by using racemic vorasidenib?

A racemic product may avoid a claim requiring at least 98% ee, but it could face separate patent claims or regulatory barriers if the approved product and related patent family cover the active S-enantiomer or therapeutic use.

Do the intermediate claims affect contract manufacturers?

Yes. Claims 2 through 8 may affect manufacturing batches, crude active pharmaceutical ingredient, and processes using the specified intermediate pairs, even if the final tablet is fully purified.

Is a Paragraph IV challenge currently possible?

The ordinary NCE filing bar generally prevents an ANDA submission for five years after FDA approval, but a Paragraph IV filing may generally be made after four years. For Voranigo, those dates correspond approximately to August 2028 and August 2029, respectively, subject to FDA listing and statutory exceptions.

References

Agios Pharmaceuticals, Inc. (2019). US Patent No. 10,414,752, Pharmaceutical compositions comprising an IDH1 inhibitor. United States Patent and Trademark Office. https://patents.google.com/patent/US10414752B2/en
U.S. Food and Drug Administration. (2024, August 6). FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2
U.S. Food and Drug Administration. (2024). Voranigo prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension resources. https://www.uspto.gov/patents/laws/patent-term-adjustment-patent-term-extension-calculators

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Rigel Pharms	REZLIDHIA	olutasidenib	CAPSULE;ORAL	215814-001	Dec 1, 2022		RX	Yes	Yes	10,414,752	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	101976	⤷ Start Trial
Australia	2015317322	⤷ Start Trial
Australia	2015317327	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,414,752