United States Patent 5,952,340: Granisetron for Post-Operative Nausea and Vomiting

U.S. Patent No. 5,952,340 protected methods of treating post-operative nausea and vomiting, or PONV, by administering granisetron. The patent’s principal commercial limitation was the use of granisetron for PONV rather than granisetron generally. Dependent claims narrowed the method by route, dose, and timing.

The patent was issued on September 14, 1999. Its statutory patent term has expired, eliminating current U.S. patent-based barriers to generic use of granisetron for the claimed PONV methods. The patent did not create composition-of-matter protection for granisetron and did not protect every use of the drug.

What does U.S. Patent 5,952,340 cover?

The patent covers a therapeutic method in which granisetron is administered to a mammal, including a human, to treat PONV.

Claim	Scope
1	Administration of granisetron to treat PONV
2	Claim 1, with granisetron adapted for intravenous administration
3	Claim 1, with a 1 mg to 3 mg unit dose
4	Claim 1, with administration pre-operatively, peri-operatively, or post-operatively
5	Claim 4, limited to pre-operative administration
6	Claim 1, with approximately 1 mg to 3 mg administered pre-operatively
7	Claim 1, with approximately 1 mg to 3 mg administered peri-operatively
8	Claim 1, with approximately 1 mg to 3 mg administered post-operatively

The independent claim is claim 1. Claims 2 through 8 depend on claim 1 and add limitations. A practice that falls within a dependent claim must also satisfy every limitation of claim 1.

How should claim 1 of Patent 5,952,340 be construed?

Claim 1 has four central elements:

A method of treatment.
A mammalian patient, including a human.
The patient has, or is at risk of, post-operative nausea and vomiting.
Granisetron is administered to that patient.

The claim is a method-of-treatment claim, not a product claim. It does not claim granisetron as a chemical compound, a pharmaceutical composition, a vial, a tablet, or an infusion device.

The claim also does not expressly require:

Intravenous delivery;
A specified dose;
A specified timing window;
A particular formulation;
A particular surgical procedure;
A particular patient age;
Combination treatment with a corticosteroid or another antiemetic; or
A stated degree of clinical improvement.

Subject to ordinary claim-construction principles, claim 1 is broader than claims 2 through 8 because it does not specify the route, dose, or perioperative timing.

What limitations do the dependent claims add?

What does claim 2 protect?

Claim 2 requires intravenous administration. The accused product or treatment must be adapted for IV delivery, and the administration must be performed in a manner that satisfies the claim.

An IV granisetron injection used for PONV would be the clearest technical example. Oral granisetron would not satisfy the express IV limitation of claim 2.

What does claim 3 protect?

Claim 3 requires a 1 mg to 3 mg unit dose. The term “unit dose” focuses on the amount administered as a discrete dose rather than merely the total amount used during an entire hospitalization.

A 1 mg, 2 mg, or 3 mg administered dose would fall within the numerical range, subject to the interpretation of the claim and the evidence concerning dosage measurement. A dose below 1 mg or above 3 mg would not literally satisfy the stated range.

What do claims 4 and 5 protect?

Claim 4 covers three administration periods:

Before surgery;
During the operative period; or
After surgery.

Claim 5 narrows claim 4 to pre-operative administration. It excludes peri-operative and post-operative administration as independent alternatives under its express wording.

What do claims 6 through 8 protect?

Claims 6, 7, and 8 combine the 1 mg to 3 mg range with a specific timing period:

Claim 6: approximately 1 mg to approximately 3 mg pre-operatively;
Claim 7: approximately 1 mg to approximately 3 mg peri-operatively;
Claim 8: approximately 1 mg to approximately 3 mg post-operatively.

These claims create narrower claim positions than claim 1. They would generally be easier to design around by changing the dose, administration timing, or both.

How broad is the patent’s practical infringement scope?

The practical scope is narrower than the independent claim’s wording may suggest because method-of-treatment infringement requires proof of the claimed clinical use and administration.

Conduct	Likely relevance to Patent 5,952,340
Manufacturing granisetron without using it for PONV	Generally outside the claims
Selling granisetron for chemotherapy-induced nausea and vomiting only	Generally outside the PONV limitation
Administering IV granisetron for PONV	Potentially within claims 1 and 2
Administering 1 mg to 3 mg for PONV	Potentially within claims 1 and 3
Administering 1 mg to 3 mg before surgery	Potentially within claims 1, 3, 4, 5, and 6
Administering more than 3 mg for PONV	Potentially within claim 1, but not literally within claims 3 or 6 through 8
Administering oral granisetron for PONV	Potentially within claim 1, but outside the express IV limitation of claim 2
Using granisetron for chemotherapy-induced nausea and vomiting	Outside the claim’s express PONV limitation
Marketing a vial without instructions or intent directed to PONV	Lower method-claim exposure than direct PONV promotion

The strongest commercial enforcement position would have involved a sponsor or manufacturer that expressly promoted granisetron for PONV, particularly IV use at 1 mg to 3 mg around surgery.

When did U.S. Patent 5,952,340 expire?

The patent was issued September 14, 1999. Its ordinary U.S. term ran from the applicable nonprovisional filing date and was subject to the patent-term rules in 35 U.S.C. § 154.

Public patent records identify the patent as expired based on the end of its statutory term. The commonly reported expiration date is December 6, 2016. Any patent-term adjustment or terminal-disclaimer issue would need to be checked against the USPTO patent file for a formal day-level determination, but the patent is no longer enforceable as a live U.S. patent.[1][2]

Event	Date
U.S. patent application filing	December 6, 1996, as reported in public patent records
Patent issued	September 14, 1999
Approximate statutory expiration	December 6, 2016
Current enforcement status	Expired

The expiration ended the patent’s ability to block post-expiration practice of the claimed PONV methods. It did not invalidate historical infringement claims accruing before expiration, subject to applicable limitations periods and other defenses.

What patents protected granisetron before Patent 5,952,340?

Patent 5,952,340 was a use patent in a broader granisetron patent family and did not provide the original chemical protection for granisetron.

Composition-of-matter protection

U.S. Patent No. 4,906,755 is associated with earlier granisetron protection. That patent covered granisetron-related chemical subject matter and pharmaceutical use. Its term expired years before Patent 5,952,340 became commercially important.[3]

The expiration of the composition patent opened the active ingredient to generic development. Later patents could still protect particular uses, formulations, manufacturing processes, or dosage regimens, but those patents could not restore exclusive control over granisetron as a molecule.

Use protection

Patent 5,952,340 addressed PONV. Its value depended on whether the relevant product labeling, promotional conduct, physician use, and generic entry strategy implicated that indication.

Formulation and manufacturing protection

Granisetron products may also have been covered by separate patents involving:

Injectable formulations;
Stabilized granisetron solutions;
Granisetron hydrochloride compositions;
Pharmaceutical salts;
Container and delivery systems;
Manufacturing or purification methods; and
Oral dosage forms.

Those patents must be analyzed separately. Patent 5,952,340 does not claim a formulation or manufacturing process. A formulation patent could have created a separate infringement risk even after the PONV method patent expired.

What was the Orange Book status of Patent 5,952,340?

Method-of-use patents can be listed in the FDA Orange Book when they correspond to an approved use of the listed drug and satisfy FDA listing requirements. Listing does not determine whether a patent is valid or infringed.

The Orange Book analysis for granisetron must distinguish among:

Kytril tablets;
Kytril injection;
Generic granisetron tablets;
Generic granisetron injection; and
The approved indications associated with each dosage form.

A patent claiming PONV would have had Orange Book significance only if the claimed use corresponded to an FDA-approved use for the relevant listed product. If PONV was not an approved indication for the listed granisetron product, listing eligibility would be more limited, and the patent would have had less direct Hatch-Waxman leverage.

The current business effect is limited because Patent 5,952,340 has expired. An expired patent no longer requires a Paragraph IV certification by a new ANDA applicant as a live patent barrier, although historical certifications and litigation records may remain relevant to the product’s generic-entry history.[4][5]

Did Patent 5,952,340 create Paragraph IV risk?

What is a Paragraph IV challenge?

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The certification can trigger patent litigation under the Hatch-Waxman Act.[4]

For Patent 5,952,340, a generic applicant could have challenged the patent by asserting that:

The PONV method was anticipated;
The claimed method was obvious in view of earlier antiemetic and granisetron disclosures;
The claim lacked adequate written description or enablement;
The claims were indefinite;
The proposed generic labeling did not induce infringement;
The patent was improperly listed; or
The generic product would be used for non-PONV indications.

The most commercially important defense for a generic manufacturer would likely have been a label-based non-infringement position. Granisetron has uses outside PONV, particularly chemotherapy-associated nausea and vomiting. A generic applicant could seek a label that omitted the patented PONV use, depending on FDA-approved labeling and the applicable regulatory framework.

Were generic launch scenarios available?

The principal generic launch scenarios were:

Full-label generic launch

A generic sponsor could market granisetron with labeling that included PONV if no enforceable patent remained and FDA approval covered that use.

Carved-out labeling

A sponsor could seek approval for non-PONV uses while omitting PONV language, where permitted by the FDA’s labeling rules. This approach would reduce direct inducement exposure but would not necessarily eliminate all litigation risk if the reference product’s use was widely promoted or if the remaining label encouraged the patented method indirectly.[5]

Post-expiration launch

After December 2016, the patent no longer presented a live U.S. method-of-use barrier. Generic manufacturers could enter without designing around the dose or surgical timing limitations of claims 3 through 8, subject to any separate unexpired patent rights.

How strong was the patent estate?

Claim strength

The patent estate was moderate in commercial breadth but narrow in technical subject matter.

Factor	Assessment
Chemical composition protection	None in Patent 5,952,340
Core use	PONV treatment with granisetron
Route limitation	IV only in claim 2
Dose limitation	1 mg to 3 mg in claims 3 and 6-8
Timing limitation	Expressly addressed in claims 4-8
Formulation protection	None apparent from the stated claims
Manufacturing protection	None apparent from the stated claims
Biosimilar relevance	None
Current blocking power	None after expiration

Claim 1 was the key claim because it did not require IV delivery or a numerical dose. Claims 2 through 8 supplied fallback positions but were more vulnerable to design-around strategies.

Validity considerations

Potential validity issues would have included:

Prior disclosures of granisetron for nausea and vomiting;
Earlier clinical work involving postoperative patients;
Obviousness of selecting granisetron for PONV;
Adequacy of clinical support across the full claim scope;
The distinction between treatment and prophylaxis; and
Whether the claims provided sufficient support for all mammalian patients and all administration routes.

The broadest claim could have faced a stronger obviousness challenge than the narrower dose-and-timing claims. Conversely, clinical evidence demonstrating a meaningful PONV benefit at the claimed doses could have supported the narrower claims.

What litigation affected the patent?

The patent’s litigation significance would depend on any ANDA filing, Paragraph IV notice, district-court complaint, settlement, or appellate decision associated with the relevant granisetron product.

Patent 5,952,340 should not be treated as an isolated asset. A complete litigation review would normally examine:

FDA Orange Book patent listings;
ANDA litigation under 21 U.S.C. § 355(j);
District Court filings;
Federal Circuit appeals;
Patent-term calculations;
Settlement agreements;
License agreements; and
Any covenant not to sue or consent judgment.

No separate biosimilar pathway applies. Granisetron is a small-molecule drug regulated through the ANDA framework rather than the biologics license application and biosimilar pathway.[4][6]

Were licensing deals associated with the patent?

The patent was associated with the granisetron commercial franchise, historically marketed under the Kytril brand. A patent assignment, corporate restructuring, or product commercialization agreement does not necessarily establish a license to third parties.

A reliable licensing conclusion requires review of recorded USPTO assignments, Securities and Exchange Commission filings, transaction agreements, and court records. The patent’s expiration means that any historic license has little present exclusionary value unless it included separate continuing obligations, royalties, settlement restrictions, or rights covering other intellectual property.

What geographic coverage did the patent have?

Patent 5,952,340 provided rights only in the United States. It did not directly control:

European use of granisetron;
Canadian PONV treatment;
Japanese granisetron products;
Manufacturing outside the United States;
Importation into countries without corresponding patent protection; or
Foreign formulations covered by separate national patents.

The relevant foreign family members would require separate review of filing dates, national-phase prosecution, grant status, term, supplementary protection certificates, and local claim scope.

Does the patent create biosimilar risk?

No. Granisetron is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is generic substitution through an ANDA, not biosimilar approval under the Public Health Service Act.

The commercial risk therefore comes from:

ANDA-approved generic injection;
ANDA-approved oral products;
Hospital purchasing contracts;
Wholesale price competition;
Formulary substitution; and
Potential use of generic granisetron in PONV despite labeling distinctions.

What is the current commercial significance?

The patent has no current exclusionary value because it expired in 2016. Its historical value was concentrated in the period after composition-of-matter protection ended and before generic competition became established.

The product-level revenue exposure would have been linked to:

IV granisetron used in hospitals;
Surgical-center antiemetic protocols;
PONV prophylaxis;
Branded Kytril pricing; and
Any commercial reliance on 1 mg to 3 mg perioperative dosing.

Patent 5,952,340 could have protected a commercially important use without protecting the drug itself. That distinction limited its ability to prevent generic entry across all granisetron indications.

Key Takeaways

U.S. Patent 5,952,340 claimed treatment of PONV with granisetron.
Claim 1 was the broadest claim and did not require a specific route, dose, or timing.
Claims 2 through 8 narrowed the method by IV delivery, 1 mg to 3 mg dosing, and pre-operative, peri-operative, or post-operative administration.
The patent did not claim granisetron as a molecule, a formulation, or a manufacturing process.
The patent’s reported U.S. expiration was December 6, 2016.
It is no longer an enforceable U.S. barrier to generic granisetron use.
Historical Paragraph IV and Orange Book issues would have depended on the approved labeling and product-specific patent listings.
Granisetron has no biosimilar pathway because it is a small-molecule drug.
Any current freedom-to-operate analysis must focus on separate formulation, delivery, manufacturing, or later-use patents rather than Patent 5,952,340.

Frequently Asked Questions

What drug does U.S. Patent 5,952,340 protect?

It protects a method of using granisetron to treat post-operative nausea and vomiting. It does not protect granisetron as a chemical compound.

Does Patent 5,952,340 cover oral granisetron?

Claim 1 is not limited to intravenous administration, so oral use could implicate claim 1 if all claim elements were satisfied. Claim 2, however, is expressly limited to IV administration.

Does the patent cover a 4 mg dose?

A 4 mg dose would not literally satisfy the 1 mg to 3 mg limitation in claims 3 and 6 through 8. It could still be relevant to claim 1, which has no express dose limitation.

Can a generic manufacturer sell granisetron for chemotherapy-induced nausea and vomiting?

Patent 5,952,340 is directed to PONV, not chemotherapy-induced nausea and vomiting. Because the patent has expired, it does not currently restrict that generic use.

Are there still active granisetron patents in the United States?

Patent 5,952,340 is expired. Separate patents covering a particular formulation, delivery system, manufacturing process, or later-developed use would need independent status and claim analysis.

References

United States Patent and Trademark Office. (1999). U.S. Patent No. 5,952,340, Use of granisetron for treating post-operative nausea and vomiting.
United States Code, 35 U.S.C. § 154. Patent term.
United States Patent and Trademark Office. (1989). U.S. Patent No. 4,906,755, Granisetron and related pharmaceutical compounds.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
Public Health Service Act, 42 U.S.C. § 262. Biologics licensing and biosimilar products.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9305593	Mar 18, 1993

PCT Information
PCT Filed	March 15, 1994	PCT Application Number:	PCT/EP94/00820
PCT Publication Date:	September 29, 1994	PCT Publication Number:	WO94/21257

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	511	⤷ Start Trial
African Regional IP Organization (ARIPO)	9400626	⤷ Start Trial
Austria	230596	⤷ Start Trial
Australia	6377494	⤷ Start Trial
Australia	676032	⤷ Start Trial
Canada	2158354	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,952,340