Details for Patent: 9,850,246

Which drugs does patent 9,850,246 protect, and when does it expire?

Patent 9,850,246 protects QULIPTA and is included in one NDA.

This patent has three patent family members in two countries.

Summary for Patent: 9,850,246

Title:	Process for making CGRP receptor antagonists
Abstract:	The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.
Inventor(s):	Frank Chen, Carmela Molinaro, W. Peter Wuelfing, Nobuyoshi Yasuda, Jianguo Yin, Yong-Li Zhong, Joseph Lynch, Teresa Andreani
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US14/854,760
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,850,246
Patent Claim Types: see list of patent claims	Compound;

US Patent 9,850,246: Atogepant Crystalline Monohydrate Scope, Claims, Expiration, and Patent Landscape

US Patent 9,850,246 protects a specific crystalline monohydrate of atogepant, the active pharmaceutical ingredient in QULIPTA. The patent does not broadly claim every form of atogepant. Its enforceable scope is centered on the solid-state form identified by the claimed monohydrate, thermal behavior, and powder X-ray diffraction pattern. The patent was assigned to Allergan Pharmaceuticals International DAC and is part of the US atogepant patent estate now associated with AbbVie following AbbVie’s acquisition of Allergan.

The patent is commercially important because a generic developer could avoid infringement by producing an anhydrous form, a different hydrate, an amorphous form, a salt, or another polymorph, provided the product does not convert into the claimed monohydrate during manufacture, storage, formulation, or use.

What drug does US Patent 9,850,246 protect?

US 9,850,246 protects crystalline atogepant monohydrate.

The lengthy chemical name in the claims identifies the stereochemically defined small molecule now known as atogepant. Atogepant is an oral, small-molecule calcitonin gene-related peptide, or CGRP, receptor antagonist marketed by AbbVie as QULIPTA in the United States for the preventive treatment of migraine in adults.

Item	Information
Active ingredient	Atogepant
Brand	QULIPTA
Drug class	Oral CGRP receptor antagonist
Dosage forms	Tablets
US approval	September 28, 2021
Original sponsor	Allergan Pharmaceuticals International DAC
Current commercial owner	AbbVie
Patent at issue	US 9,850,246
Patent type	Solid-state form and crystalline monohydrate
Issued	December 26, 2017
Listed product	QULIPTA, subject to FDA Orange Book listing data

The claimed material is a monohydrate. That means the crystal structure incorporates approximately one molecule of water per molecule of atogepant, although the legally relevant question is whether the accused material meets the claim limitations, not whether its measured water content is exactly stoichiometric in every sample.

What are the claims of US Patent 9,850,246?

The patent has three claims, with claim 1 functioning as the principal composition claim.

Claim	Scope	Practical significance
1	Crystalline atogepant monohydrate	Broadest claim in the patent
2	Claim 1 material having DSC extrapolated onset of about 144°C and peak melting temperature of about 175°C	Thermal characterization of the claimed form
3	Claim 1 material having specified XRPD d-spacings	Structural fingerprint for the claimed crystal form

Claim 1: crystalline atogepant monohydrate

Claim 1 requires four central attributes:

1. The molecule must be the claimed stereoisomer of atogepant.
2. It must be crystalline.
3. It must be a monohydrate.
4. It must have the chemical composition recited in the claim.

The claim is narrower than a claim to atogepant itself. It does not cover all crystalline atogepant, all hydrates of atogepant, or all pharmaceutical compositions containing atogepant.

The claim also does not expressly require a particular XRPD pattern or melting point. Those characteristics appear in claims 2 and 3. A material may therefore infringe claim 1 even if it does not satisfy every numerical limitation in the dependent claims, provided it is the claimed crystalline monohydrate.

Claim 2: differential scanning calorimetry limitations

Claim 2 requires the claim 1 monohydrate to have:

• A DSC extrapolated onset melting temperature of about 144°C; and
• A DSC peak melting temperature of about 175°C.

The use of "about" introduces a range that would be determined through claim construction and technical evidence. Relevant variables include heating rate, sample preparation, instrument calibration, atmosphere, water loss, and analytical method.

Claim 2 is a narrower characterization claim. It may be useful in litigation where the accused product has a DSC trace consistent with the patented form. It is less likely to be decisive by itself because thermal events can shift with testing conditions and sample history.

Claim 3: powder X-ray diffraction limitations

Claim 3 requires the monohydrate to have d-spacings, measured by Cu K-alpha XRPD, of approximately:

12.7, 8.9, 8.1, 7.4, 6.4, 5.2, 4.9, 4.8, and 4.0 angstroms.

These peaks operate as a crystallographic identity profile. The claim does not merely require one isolated diffraction peak. It recites a series of d-spacings that, considered together, are intended to distinguish the claimed monohydrate from other solid forms.

XRPD testing is likely to be the principal analytical method in a generic dispute. The analysis would normally compare the accused material’s diffraction pattern with the claimed pattern while accounting for peak shifts, preferred orientation, instrument resolution, impurities, crystallinity, and sample hydration.

How strong is the patent estate for atogepant?

US 9,850,246 is strong against a manufacturer that uses the same crystalline monohydrate in its active pharmaceutical ingredient or finished tablets. It is weaker against a competitor that uses a different solid form and can demonstrate that the product does not convert to the claimed monohydrate.

Risk category	Risk to generic developer	Reason
Use of the exact claimed monohydrate	High	Direct product overlap
Use of the claimed XRPD form	High	Claim 3 supplies a specific analytical fingerprint
Use of a different polymorph	Moderate to low	Depends on conversion or overlap with claim 1
Use of amorphous atogepant	Lower	Amorphous material is not crystalline
Use of a non-monohydrate hydrate	Lower	Claim requires monohydrate
Use of an anhydrous form	Lower	Claim requires incorporated water
Formulation containing the patented API form	High	Product-by-process and composition issues may arise
Manufacturing process that converts API to the monohydrate	High	Infringement may occur before formulation

The principal weakness is claim construction around "crystalline" and "monohydrate." A competitor may attempt to establish that its material is a different hydrate, a solid solution, an amorphous-crystalline mixture, or a polymorph with overlapping but non-identical analytical characteristics.

When does US Patent 9,850,246 expire?

The patent’s ordinary term is expected to run to approximately March 2034, based on the earliest claimed priority date in the relevant family. The precise expiration date depends on the patent’s effective filing date, any patent-term adjustment, terminal disclaimer, and any patent-term extension.

Milestone	Date or period
Earliest family priority	Approximately March 2014
US patent issue	December 26, 2017
Base 20-year term	Approximately March 2034
Potential adjustment	Depends on USPTO prosecution history
Potential extension	Must be confirmed from FDA and USPTO records
Market exclusivity	Separate from patent expiration

Patent expiration does not automatically equal generic launch permission. A generic applicant must also address Orange Book-listed patents, FDA exclusivity, regulatory approval timing, and any litigation-related stay.

The patent is not a biologic patent and does not create biosimilar exclusivity. Atogepant is a small molecule regulated through the abbreviated new drug application pathway.

What is the Orange Book status of US 9,850,246?

US 9,850,246 has been associated with the QULIPTA patent estate and is relevant to the FDA’s Orange Book patent framework for atogepant tablets. Orange Book listing status can change through FDA administrative updates, patent delistings, corrections, and product-specific listing changes.

An Orange Book listing gives the innovator a statutory mechanism to sue an ANDA applicant after receiving a Paragraph IV certification. If the innovator files a timely infringement action, FDA approval may be subject to a 30-month stay, subject to statutory exceptions and litigation developments under the Hatch-Waxman Act.

The practical question for a generic applicant is not only whether US 9,850,246 is listed. It is whether the proposed product, API form, labeling, and manufacturing process would infringe the listed claim.

What Paragraph IV challenges could affect atogepant?

A Paragraph IV applicant would likely attack the patent on several grounds:

Invalidity arguments

Potential arguments include:

• Lack of anticipation based on earlier disclosures of the same monohydrate.
• Obviousness based on known atogepant solid forms, routine hydrate screening, and predictable crystallization methods.
• Lack of written description or enablement for the full scope of "about" limitations.
• Indefiniteness involving the boundaries of the claimed XRPD and DSC parameters.
• Double-patenting if related applications contain overlapping solid-form claims.

Solid-form patents often face an obviousness challenge focused on whether a skilled pharmaceutical scientist would have had a reasonable expectation of obtaining the claimed hydrate and whether the claimed form provides unexpected properties.

Noninfringement arguments

A generic developer could argue that:

• Its API is anhydrous.
• Its API is a different polymorph.
• Its material is a different hydrate.
• The claimed XRPD pattern is absent.
• Water is present only as residual moisture and is not part of the crystal lattice.
• The finished dosage form does not contain the claimed crystal form.

The strongest defense would normally combine an alternative solid-form process with batch-specific XRPD, thermal analysis, water-content testing, and stability data.

What formulation and method-of-use patents protect QULIPTA?

US 9,850,246 is a drug-substance solid-form patent, not a principal method-of-use patent. It does not, on its face, claim migraine prevention broadly, a dosing regimen, a tablet excipient system, or a manufacturing process.

The broader QULIPTA patent landscape may include separate patents covering:

• Atogepant composition of matter.
• Crystalline and hydrated forms.
• Pharmaceutical compositions.
• Tablet formulations.
• Methods of treating or preventing migraine.
• Dosing schedules and patient populations.
• Manufacturing processes and intermediates.

A generic applicant must evaluate each Orange Book-listed patent separately. An ANDA “skinny label” strategy may avoid a method-of-use patent if the omitted indication is carved out properly, but it generally does not avoid a composition or solid-form patent covering the API used in the generic product.

Which companies are challenging atogepant exclusivity?

Publicly available patent records should be reviewed for specific ANDA notices, district-court complaints, declaratory-judgment actions, and Federal Circuit proceedings. The identity of a Paragraph IV challenger cannot be inferred from the existence of US 9,850,246 alone.

No biosimilar competition is relevant because atogepant is a chemically synthesized small molecule. Competition would arise through ANDA applicants producing generic atogepant tablets.

The most commercially plausible generic launch paths are:

1. A Paragraph IV challenge to the remaining Orange Book estate.
2. A launch after patent expiration.
3. A noninfringing alternative solid form.
4. A settlement permitting an agreed future launch date.
5. A licensed or authorized-generic arrangement.

How does this patent compare with composition-of-matter protection?

Protection type	Typical scope	Relevance to atogepant
Composition of matter	Covers the molecule and stereochemical structure	Usually the strongest foundational patent
Solid form	Covers a polymorph, hydrate, or crystal	US 9,850,246
Formulation	Covers dosage form or excipient system	May restrict tablet design
Method of use	Covers treatment or prevention method	May affect label strategy
Manufacturing process	Covers synthesis or purification	Can create API supply risk
Regulatory exclusivity	Blocks FDA approval for a defined period	Separate from patent rights

US 9,850,246 is narrower than a composition-of-matter patent but can be commercially significant because the claimed monohydrate may be the form used in the approved product. A generic cannot avoid the patent merely by changing excipients if it continues to use the patented API crystal.

What manufacturing and geographic risks exist?

The patent is a US right. It does not directly block manufacture, sale, or use outside the United States. US exposure may still arise where:

• The patented API is imported into the United States.
• Finished tablets containing the patented form are imported.
• A US-based affiliate sells or supplies the product.
• A process performed abroad results in importation of a product covered by a US patent.
• The product is made abroad using a patented US process, subject to the statutory scope of process claims.

The main manufacturing control point is solid-form conversion. Drying temperature, solvent selection, water activity, milling, granulation, compression, and storage humidity can change the solid state. A noninfringing API could potentially convert into the patented monohydrate during downstream processing or shelf storage.

What is the commercial exposure from delayed generic entry?

QULIPTA is positioned in the preventive migraine market alongside injectable CGRP antibodies and other oral CGRP antagonists. The commercial value of the patent depends on:

• The duration of protection for the full Orange Book estate.
• QULIPTA prescription and net-sales growth.
• The number of approved generic strengths.
• Generic substitution rates after launch.
• Competing products, including Nurtec ODT, Ubrelvy, Aimovig, Ajovy, and Emgality.
• Any authorized-generic or settlement arrangement.

A solid-form patent can preserve commercial protection after a composition patent becomes vulnerable if the approved product consistently uses the claimed form. Its value is highest when the form is stable, reproducible, and difficult to replace without reformulation or regulatory bridging.

Key Takeaways

• US 9,850,246 covers crystalline atogepant monohydrate, not every form of atogepant.
• Claim 1 is the principal product claim.
• Claim 2 adds DSC melting-point limitations.
• Claim 3 adds a nine-peak Cu K-alpha XRPD profile.
• The patent is relevant to QULIPTA, AbbVie’s oral atogepant product.
• The expected base patent term runs to approximately March 2034, subject to USPTO patent-term adjustment and any applicable extension.
• A generic developer using the same monohydrate faces substantial infringement risk.
• Anhydrous, amorphous, alternative hydrate, or different polymorph strategies may reduce risk but require analytical and stability evidence.
• Atogepant is a small molecule, so generic competition proceeds through ANDA and Paragraph IV mechanisms, not biosimilar procedures.
• The full commercial assessment requires review of all QULIPTA Orange Book listings, related patent families, litigation, and any settlement agreements.

FAQs

Does US 9,850,246 cover atogepant tablets?

It can cover tablets containing the claimed crystalline atogepant monohydrate, but the patent claims the solid form rather than a particular tablet excipient composition.

Can a generic use anhydrous atogepant?

Potentially, if the product remains anhydrous and does not convert into the patented monohydrate during manufacturing, storage, or use. The generic must assess the full patent estate separately.

Is US 9,850,246 a method-of-use patent?

No. The quoted claims are directed to a crystalline monohydrate and its DSC and XRPD characteristics.

Does this patent block atogepant sales outside the United States?

No. US 9,850,246 is territorially limited to the United States, although parallel foreign patents may protect corresponding solid forms in other jurisdictions.

What testing is most important in an infringement dispute?

XRPD using Cu K-alpha radiation is central to claim 3. DSC, water-content analysis, thermogravimetric analysis, microscopy, and solid-state characterization would also be relevant to determining whether the material is the claimed crystalline monohydrate.

References

1. United States Patent and Trademark Office. (2017). US Patent No. 9,850,246: Crystalline form of an atogepant compound. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2021). QULIPTA (atogepant) prescribing information. FDA.

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. United States Code. (2023). 35 U.S.C. §§ 154, 156, 271, and 282. U.S. House of Representatives, Office of the Law Revision Counsel.

5. Allergan Pharmaceuticals International DAC. (2015). Patent family disclosures relating to crystalline forms of atogepant. United States Patent and Trademark Office.

Drugs Protected by US Patent 9,850,246

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Abbvie	QULIPTA	atogepant	TABLET;ORAL	215206-001	Sep 28, 2021		RX	Yes	No				Y
Abbvie	QULIPTA	atogepant	TABLET;ORAL	215206-002	Sep 28, 2021		RX	Yes	No				Y
Abbvie	QULIPTA	atogepant	TABLET;ORAL	215206-003	Sep 28, 2021		RX	Yes	Yes				Y

International Family Members for US Patent 9,850,246

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2849568
European Patent Office	3430906
World Intellectual Property Organization (WIPO)	2013169348