US Patent 10,525,033: Amisulpride Composition Claims, Scope, Expiry and Generic Entry Risk

US Patent 10,525,033 protects low-dose amisulpride pharmaceutical compositions, with its strongest commercial coverage directed to injectable formulations containing less than 50 mg per dose and a citrate buffer. The narrowest and most commercially concrete claims cover a 0.25% w/v intravenous formulation containing citric acid monohydrate, trisodium citrate dihydrate, and sodium chloride. The patent does not claim amisulpride as a molecule, conventional high-dose oral amisulpride products, or every possible injectable formulation.

The principal infringement risk concerns an injectable product containing 2.5 mg, 5 mg, or another dose below 50 mg, particularly where the formulation uses a citrate buffer. The claims extend beyond injection to oral, sublingual, intranasal, topical, transdermal, and rectal dosage forms, but those claims are materially broader and may face greater validity and prior-art scrutiny.

What does US Patent 10,525,033 cover?

The patent claims pharmaceutical compositions containing amisulpride and a pharmaceutically acceptable carrier. Its claim architecture has two independent composition claims:

Claim	Core limitation	Commercial significance
1	Amisulpride at 2.5 mg or 5 mg per dose plus a pharmaceutically acceptable carrier	Broad low-dose composition claim
17	Intravenous amisulpride below 50 mg per dose plus a citrate buffer	Main injectable formulation claim
2-16	Narrower versions of claim 1	Dosage form, stereochemistry, salt and administration-route limitations
18-26	Narrower versions of claim 17	Dose ranges, exact doses, salt, stereochemistry and buffer components

Claim 1 is unusual because it covers two discrete dosage amounts, 2.5 mg and 5 mg, rather than a continuous dose range. Claims 2 and 3 separately preserve those two dose alternatives.

Claim 17 is broader in dose but narrower in route and excipient system. It covers intravenous compositions containing less than 50 mg per dose and a citrate buffer. Claims 18-23 progressively narrow the dose, including 1-35 mg, 1-20 mg, 2.5-20 mg, 2.5 mg, 5 mg, and 20 mg.

How broad are the independent claims?

Claim 1: low-dose amisulpride composition

Claim 1 requires:

Amisulpride;
An amount of 2.5 mg per dose or 5 mg per dose; and
A pharmaceutically acceptable carrier.

The claim does not require:

Intravenous administration;
A citrate buffer;
A specific pH;
A specific salt;
(S)-amisulpride;
A particular concentration;
A particular vial, syringe, ampoule, tablet, spray or patch;
A nausea-and-vomiting indication.

The carrier limitation is broad. A carrier may include water, saline, buffers, excipients, stabilizers, solvents, preservatives or solid dosage-form ingredients, depending on the formulation. The claim therefore reaches more than the marketed injectable product if the accused product contains exactly 2.5 mg or 5 mg of amisulpride per dose.

The main claim-construction issue is the meaning of “per dose.” A package containing multiple units would likely be assessed by the amount delivered in each intended dose, not merely the total amount in the container. A 10 mg vial administered as two 5 mg doses could present a different issue from a vial intended to deliver a single 10 mg dose.

Claim 17: intravenous citrate-buffered composition

Claim 17 requires:

A pharmaceutical composition;
Formulation for intravenous injection;
Amisulpride in an amount below 50 mg per dose; and
A citrate buffer.

Unlike claim 1, claim 17 is not limited to 2.5 mg or 5 mg. It can cover any amount below 50 mg, subject to the ordinary meaning of “comprising” and the other limitations. Claims 18-23 identify specific subranges and doses.

The claim does not expressly require:

(S)-amisulpride;
A salt form;
Sodium chloride;
A particular pH;
The exact excipient concentrations in claim 11;
A specific clinical use.

A competing intravenous product containing 1 mg, 10 mg, 20 mg, or 35 mg of amisulpride and a citrate buffer could fall within claim 17 even if it does not match the marketed formulation.

What formulations are protected by US 10,525,033?

The patent creates several levels of formulation coverage.

Exact formulation coverage

Claim 11 is the most specific composition claim. It requires:

0.25% w/v amisulpride;
0.935% w/v citric acid monohydrate;
1.632% w/v trisodium citrate dihydrate;
0.18% w/v sodium chloride; and
A pH of 4-7.

Claim 10 covers the same general component system but does not require the exact concentrations of claim 11. Claim 9 requires the three excipients, while claim 8 requires a citrate buffer.

This creates a nested structure:

Scope level	Required formulation elements
Claim 7	Intravenous amisulpride
Claim 8	Intravenous amisulpride plus citrate buffer
Claim 9	Citrate buffer containing citric acid monohydrate, trisodium citrate dihydrate and sodium chloride
Claim 10	0.25% w/v amisulpride, those excipients and pH 4-7
Claim 11	Exact concentrations of amisulpride and excipients

A generic or follow-on product that avoids one exact concentration may still infringe claims 8, 9 or 10 if it retains the broader limitations.

Non-injectable formulations

Claims 12-16 extend claim 1 to:

Oral administration;
Sublingual administration;
Intranasal administration;
Topical administration;
Transdermal administration; and
Rectal administration.

These claims are route-specific but do not add a detailed dosage-form or excipient requirement. They could cover a low-dose oral tablet, sublingual film, nasal spray, topical composition, transdermal system or rectal dosage form containing 2.5 mg or 5 mg of amisulpride.

Their practical value depends on whether such low-dose products are commercially developed and whether earlier amisulpride disclosures disclose the same dose and route combination.

Does the patent cover (S)-amisulpride and salts?

Yes. Claims 4 and 24 cover (S)-amisulpride, while claims 5 and 25 cover a pharmaceutically acceptable salt form.

These are dependent claims and do not replace the broader parent claim. The patent therefore has layered protection:

Racemic or unspecified amisulpride under claims 1 and 17;
(S)-amisulpride under claims 4 and 24;
Salt forms under claims 5 and 25;
(S)-amisulpride salt combinations through the dependency structure.

The distinction matters because an accused product may avoid one stereochemical or salt limitation while remaining within claim 1 or claim 17. Conversely, a product using a specific salt or enantiomer may trigger additional dependent claims.

When does US Patent 10,525,033 lose exclusivity?

The patent’s nominal expiration date is July 19, 2037, based on the underlying priority timeline publicly associated with the patent family. The enforceable term can differ if the patent received patent-term adjustment, patent-term extension, disclaimer, or other term modification. The United States Patent and Trademark Office patent record controls the final expiration calculation. [1]

Event	Date or status
US patent	10,525,033
Issue date	January 7, 2020
Nominal expiration	July 19, 2037
Product association	Amisulpride injection, marketed as Barhemsys
Regulatory sponsor	Acacia Pharma, later acquired by Eagle Pharmaceuticals
FDA approval of Barhemsys	February 26, 2020

Patent expiration does not necessarily equal the earliest possible generic launch date. A generic applicant may challenge the patent before expiry through an ANDA Paragraph IV certification. A successful challenge, settlement, invalidity ruling or noninfringement position could permit earlier entry.

What is the FDA and Orange Book status of amisulpride?

The FDA approved Barhemsys, an intravenous amisulpride product, for the prevention and treatment of postoperative nausea and vomiting in adults. The product is administered intravenously and is supplied in low-dose strengths consistent with the commercial relevance of the patent claims. [2]

The Orange Book is the relevant FDA source for listed patents and exclusivity associated with approved small-molecule products. Patent 10,525,033 has been associated with the Barhemsys patent estate. The Orange Book listing should be reviewed together with later-issued patents, use codes and any listed patent-term information because a product may be protected by several patents with different claim categories. [3]

Regulatory exclusivity and patent exclusivity are separate:

New chemical entity exclusivity generally runs for five years from approval, subject to statutory exceptions.
Barhemsys received approval in 2020.
Patent protection may extend materially beyond the regulatory exclusivity period.
A Paragraph IV ANDA challenge can address listed patents before their expiration.

What Paragraph IV challenges or litigation affect amisulpride?

The supplied claims establish the patent’s technical scope but do not establish whether a specific generic manufacturer has filed a Paragraph IV certification, received a first-filer position, entered litigation, or executed a settlement agreement.

A Paragraph IV challenge to this patent would likely target one or more of the following issues:

Anticipation by earlier disclosures of low-dose amisulpride compositions;
Obviousness based on known amisulpride products, dose reduction and routine injectable formulation work;
Written-description support for the broad dose and route combinations;
Enablement of the broad injectable claim across all doses below 50 mg and all citrate-buffer systems;
Claim construction of “per dose,” “citrate buffer” and “formulated for intravenous injection”;
Inherency or lack of criticality for the exact excipient concentrations in claims 10 and 11.

The strongest litigation position is likely to differ by claim. Claims 8-11 are narrower and easier to test analytically because they recite identifiable excipients, concentrations and pH. Claim 17 is commercially broad but potentially more exposed to validity attacks because it covers a wide dose range and any citrate buffer.

How strong is the patent estate for Barhemsys?

US 10,525,033 is important but should not be treated as the entire amisulpride patent estate. Commercial protection can also arise from:

Later-issued continuation or divisional patents;
Method-of-use patents;
Formulation patents with different excipient limitations;
Manufacturing or purification patents;
Patent rights in Europe, Japan, Canada and other regulated markets;
Regulatory exclusivity;
Trade secrets involving sterile manufacturing, analytical methods and process controls.

Method-of-use protection

The claims supplied here are composition claims. They do not require treatment of postoperative nausea and vomiting or any other therapeutic indication. A method-of-use patent, if separately listed, could create an additional barrier for a generic seeking approval for the same indication.

The composition patent may be infringed by making, using, selling, offering to sell or importing a covered product even when the label omits a patented use. The treatment indication remains relevant to FDA approval strategy and inducement theories but is not a limitation of the claims supplied.

Manufacturing and process barriers

The patent claims do not recite:

Sterile filling;
Aseptic processing;
Container-closure systems;
Specific manufacturing temperatures;
Mixing order;
Degradation controls;
Endotoxin specifications;
Batch-release methods.

A manufacturer may therefore design around the formulation claims while still encountering separate process patents, regulatory comparability requirements or technical barriers associated with sterile injectable production.

How can a generic design around US 10,525,033?

Potential design-around paths include:

Design-around strategy	Potential effect
Use a dose of 50 mg or more	Avoids claim 17’s “less than 50 mg” limitation, but may not be clinically suitable and could implicate claim 1 only if the dose is 2.5 or 5 mg
Avoid citrate buffer	May avoid claims 8-11 and 17-26
Use a non-citrate buffering system	May reduce literal infringement risk, subject to claim construction and equivalents
Use a different pH and excipient profile	May avoid claims 10-11 but not necessarily claims 8-9 or 17
Use a dose other than 2.5 mg or 5 mg	Avoids claim 1 and its dependents, but not necessarily claim 17
Use a non-intravenous route	Avoids claim 17 and its dependents, but may implicate claims 12-16
Use a different dosage form	Relevant only if the new form avoids the claimed dose and route limitations
Pursue invalidity rather than design-around	May eliminate broad or narrow claims if prior art or disclosure defects are demonstrated

The most direct formulation design-around is a non-citrate intravenous formulation below 50 mg per dose. That approach does not eliminate potential exposure under other patents or the doctrine of equivalents.

How does US 10,525,033 compare with conventional amisulpride patents?

Conventional amisulpride patents generally focus on the active compound, stereochemistry, therapeutic uses, high-dose oral products, polymorphs, salts or manufacturing processes. US 10,525,033 is different because its commercial center is a low-dose composition, especially a buffered intravenous formulation.

Patent category	Main subject matter	Relevance to US 10,525,033
Compound patent	Amisulpride molecule or chemical class	Generally distinct and likely expired or less relevant to current low-dose entry
Stereochemistry patent	(S)-amisulpride or enantiomeric compositions	Overlaps with claims 4 and 24
Oral-use patent	Oral amisulpride treatment	May overlap with claims 12 and 1
Formulation patent	Injectable composition, buffer and excipients	Closest technology category
Method-of-use patent	Prevention or treatment of nausea and vomiting	Separate infringement and FDA-label issue
Manufacturing patent	Sterile preparation or process controls	Potential additional barrier not recited in these claims

What is the geographic coverage?

US Patent 10,525,033 provides United States rights only. Foreign protection depends on national-stage filings and granted counterparts in the relevant patent family.

Geographic risk should be assessed separately in:

European Union and United Kingdom;
Canada;
Japan;
Australia;
China;
South Korea;
Other markets where intravenous amisulpride products are commercialized or under development.

A US design-around does not establish freedom to operate elsewhere. Conversely, an expired or invalidated foreign counterpart does not affect US enforceability.

What revenue exposure does the patent create?

The patent’s revenue exposure is concentrated in the branded intravenous amisulpride market rather than the broader historical oral amisulpride market. Barhemsys is an acute-care hospital product, so the relevant commercial question is whether a generic can reproduce the clinical presentation, injectable dose, stability profile and hospital purchasing economics.

The highest-value protected features are:

Low-dose intravenous delivery;
Citrate-buffered formulation;
Exact or near-exact excipient system;
2.5 mg and 5 mg dose presentations;
FDA-approved use in postoperative nausea and vomiting.

A generic that avoids the exact claim 11 formulation may still compete if it can obtain approval with a different formulation and establish the required pharmaceutical equivalence or clinical bridge. The patent therefore creates a meaningful barrier but does not guarantee market exclusivity through 2037.

Key Takeaways

US 10,525,033 is a composition patent focused on low-dose amisulpride.
Claim 1 covers compositions containing exactly 2.5 mg or 5 mg per dose.
Claim 17 is the main broad injectable claim and covers intravenous amisulpride below 50 mg per dose with a citrate buffer.
Claims 8-11 create progressively narrower protection for a citrate-buffered formulation containing citric acid, trisodium citrate and sodium chloride.
Claim 11 recites the most specific formulation: 0.25% w/v amisulpride with exact excipient concentrations and pH 4-7.
The patent also reaches oral, sublingual, intranasal, topical, transdermal and rectal products through claims 12-16 when the dose is 2.5 mg or 5 mg.
The nominal patent expiration is July 19, 2037, subject to the official USPTO term calculation.
The supplied claims do not establish a particular Paragraph IV filing, litigation outcome or settlement agreement.
The clearest formulation design-around is a non-citrate intravenous product, although other patents and regulatory barriers may remain.
The patent protects a product architecture associated with Barhemsys, not amisulpride as a molecule.

FAQs

Does US 10,525,033 cover all amisulpride products?

No. It covers specified low-dose compositions and certain intravenous citrate-buffered compositions. It does not cover every amisulpride product or every dose.

Does a 10 mg amisulpride product infringe claim 1?

No, not based on claim 1 alone, because claim 1 recites 2.5 mg or 5 mg per dose. A 10 mg intravenous product with a citrate buffer could still fall within claim 17.

Does avoiding sodium chloride avoid the patent?

No. Claims 8 and 17 do not require sodium chloride. Claims 9-11 do require sodium chloride or more specific components, but broader claims may remain relevant.

Can a generic use a different buffer?

Possibly. A non-citrate buffer may avoid the literal “citrate buffer” limitation in claim 17 and related dependent claims, but the complete patent estate and equivalents analysis must also be considered.

Is the patent relevant to oral amisulpride tablets?

Potentially. Claims 1 and 12 can cover an oral composition containing 2.5 mg or 5 mg per dose. Higher-dose conventional oral products fall outside those claims based on the supplied language.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,525,033, Amisulpride pharmaceutical compositions.
U.S. Food and Drug Administration. (2020). Barhemsys (amisulpride) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lxo Ireland	BARHEMSYS	amisulpride	SOLUTION;INTRAVENOUS	209510-001	Feb 26, 2020		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Lxo Ireland	BARHEMSYS	amisulpride	SOLUTION;INTRAVENOUS	209510-002	Sep 1, 2020		RX	Yes	Yes	⤷ Start Trial	⤷ 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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	1004020.2	Mar 11, 2010

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011225898	⤷ Start Trial
Brazil	112012022746	⤷ Start Trial
Canada	2792392	⤷ Start Trial
China	102892407	⤷ Start Trial
Cyprus	1115485	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,525,033

Which drugs does patent 10,525,033 protect, and when does it expire?

Summary for Patent: 10,525,033