Details for Patent: 9,186,357

Which drugs does patent 9,186,357 protect, and when does it expire?

Patent 9,186,357 protects AKYNZEO and is included in two NDAs.

This patent has sixty-nine patent family members in forty-two countries.

Summary for Patent: 9,186,357

Title:	Compositions and methods for treating centrally mediated nausea and vomiting
Abstract:	Provided are compositions and methods for treating or preventing nausea and vomiting in patients undergoing chemotherapy, radiotherapy, or surgery.
Inventor(s):	Fabio Trento, Sergio Cantoreggi, Giorgia Rossi, Roberta Cannella, Daniele Bonadeo
Assignee:	Helsinn Healthcare SA
Application Number:	US14/069,927
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,186,357
Patent Claim Types: see list of patent claims	Use; Delivery; Dosage form;

U.S. Patent 9,186,357: Scope, Claims, Expiration, and Netupitant-Palonosetron Patent Landscape

U.S. Patent No. 9,186,357 protects clinical regimens combining netupitant, palonosetron, and dexamethasone for chemotherapy-induced nausea and vomiting. Its strongest commercial coverage is directed to the Akynzeo regimen: a single oral dose of approximately 300 mg netupitant and 0.5 mg palonosetron hydrochloride before chemotherapy, with dexamethasone dosing tailored to moderately or highly emetogenic chemotherapy. The patent is a method-of-treatment patent, not a composition patent, and its principal enforcement risk is directed to manufacturers, labeling, and clinical use of competing netupitant-palonosetron products.

What does U.S. Patent 9,186,357 protect?

The patent contains three principal independent claim concepts:

Claim	Core protected subject matter	Commercial relevance
1	Treating CINV with palonosetron, netupitant, and dexamethasone	Broad three-drug regimen
2	Treating CINV with netupitant and a sub-therapeutic dexamethasone dose	Steroid-sparing regimen
4	Inducing effective blood levels of palonosetron and netupitant	Pharmacokinetic and intravenous-regimen coverage

The dependent claims narrow those concepts by specifying:

• Moderately or highly emetogenic chemotherapy;
• Listed chemotherapy agents, including cisplatin, carboplatin, oxaliplatin, doxorubicin, cyclophosphamide, and irinotecan;
• Administration before chemotherapy;
• Five-day control of CINV;
• Acute and delayed CINV phases;
• Absence of emetic episodes and rescue medication;
• Single-dose administration without repeat netupitant or palonosetron dosing for at least five days;
• Oral netupitant at approximately 300 mg;
• Oral palonosetron hydrochloride at approximately 0.50 mg;
• Administration in a single combination dosage form;
• Dexamethasone at 12 mg before chemotherapy and, for highly emetogenic chemotherapy, 8 mg on days 2, 3, and 4;
• At least 70% striatal NK1-receptor occupancy 96 hours after dosing.

The patent therefore combines broad treatment claims with highly specific regimen claims that map closely to the labeled use of Akynzeo.

What are the independent claims in U.S. Patent 9,186,357?

Claim 1: Triple-drug CINV regimen

Claim 1 requires administering a regimen of:

1. Palonosetron;
2. Netupitant; and
3. Dexamethasone;

to a patient receiving chemotherapy for CINV.

The claim does not require a particular dose, dosage form, timing, chemotherapy agent, or five-day treatment period. Claims 5 through 10 narrow the chemotherapy setting, while claims 17 through 39 add response criteria, dose ranges, timing, and pharmacodynamic limitations.

A competing product or treatment protocol would generally fall within claim 1 if it uses all three agents in a CINV regimen, even if the doses or dosage forms differ from Akynzeo, subject to ordinary claim-construction and validity issues.

Claim 2: Netupitant plus reduced-dose dexamethasone

Claim 2 covers a regimen of netupitant and a sub-therapeutic dose of dexamethasone. Claim 3 defines the reduced steroid dose as approximately 50% to 70% of the minimum effective dexamethasone dose when dexamethasone is used alone against CINV.

This claim is commercially important because it reaches a steroid-sparing approach. It may cover a regimen that does not use palonosetron, unlike claims 1 and 18 through 39.

The principal interpretation issue is the meaning of "sub-therapeutic." Claim 3 provides a quantitative limitation, but claim 2 itself does not specify a numerical dose. A defendant could argue that the term is indefinite or lacks an objective boundary unless the specification and prosecution history establish how the minimum effective dose is determined.

Claim 4: Blood-level and pharmacokinetic coverage

Claim 4 covers treating CINV by inducing effective blood levels of palonosetron and netupitant. Claims 53 through 62 narrow the claim to an intravenous antiemetic regimen administered before chemotherapy and to five-day efficacy, acute and delayed control, nausea reduction, and specific chemotherapy agents.

Claim 4 is broader in functional language than a conventional dose claim. It may reach different formulations or routes if they produce the claimed pharmacological exposure. Its enforcement value depends on whether the relevant blood levels can be demonstrated and whether the accused product or treatment protocol intentionally induces them.

Which claims are strongest for Akynzeo?

The most commercially targeted claims are claims 19 through 23 and claims 33 through 39.

Claim group	Key limitations	Practical significance
18-19	Single netupitant and palonosetron doses, concomitant administration, no repeat dose for at least five days	Covers the core long-acting combination regimen
20	Netupitant 200-400 mg and palonosetron 0.25-0.75 mg	Dose-range coverage
21	Approximately 300 mg netupitant, 0.50 mg palonosetron, single oral dosage form, less than two hours before chemotherapy	Closely tracks oral Akynzeo
22	Moderately emetogenic chemotherapy and 12 mg dexamethasone before chemotherapy	Core moderate-emetogenic regimen
23	Highly emetogenic chemotherapy, 12 mg dexamethasone before chemotherapy, and 8 mg on days 2-4	Core high-emetogenic regimen
24, 29, 36	At least 70% striatal NK1-receptor occupancy at 96 hours	Pharmacodynamic protection
25-27	Acute and delayed CINV control	Therapeutic-outcome coverage
30-32, 37-39	Cisplatin, carboplatin, oxaliplatin, doxorubicin, or cyclophosphamide	Product-use and chemotherapy-specific coverage

Claims 21 through 23 are narrower than claim 1 but have greater practical infringement value because they specify the commercial dose, timing, and dosage form.

What formulations are protected by U.S. Patent 9,186,357?

The patent does not principally claim the physical combination product as a composition. It claims use of the combination in a treatment regimen.

The principal formulation-related limitation is in claim 21, which requires netupitant and palonosetron to be administered as a "single unit dosage form." This language can cover a fixed-dose combination capsule or tablet containing both active ingredients. Claim 22 and claim 23 expressly place dexamethasone in a dosage form independent of the combination unit dosage form.

The claims therefore distinguish between:

• A combination unit dosage form containing netupitant and palonosetron; and
• Separate dexamethasone administration.

That distinction is relevant to product design. A competing product containing netupitant and palonosetron in separate dosage forms may avoid claims that require a single unit dosage form, but it may still implicate broader claims such as claim 1, claim 4, or claim 19.

Claim 28 also addresses palonosetron composition by requiring that a specified palonosetron-related impurity or stereochemical component be substantially absent. This creates a product-quality limitation that may require analytical testing rather than reliance solely on the product label.

When does U.S. Patent 9,186,357 lose exclusivity?

The patent issued on November 17, 2015. Its underlying priority date is associated with the netupitant-palonosetron CINV development program and the patent is generally identified with a September 2029 expiration period. The expected ordinary patent-term endpoint is approximately September 30, 2029, subject to any applicable patent-term adjustment, terminal disclaimer, or other USPTO term calculation.

Event	Date or period
Patent grant	November 17, 2015
Patent type	Utility patent
Primary subject	Method of treating CINV
Expected ordinary expiration	Approximately September 30, 2029
Regulatory protection	Separate from patent term and must be assessed under the applicable NDA record
Generic entry	Potentially before patent expiry only through a successful challenge, settlement, license, or non-infringing route

The patent should not be analyzed in isolation. Akynzeo exclusivity also depends on other patents, FDA-listed patents, regulatory exclusivity, pediatric extensions, and any settlement agreements involving ANDA applicants.

What is the Orange Book status of U.S. Patent 9,186,357?

U.S. Patent 9,186,357 has been associated with the Akynzeo product, which contains netupitant and palonosetron hydrochloride. The Orange Book listing is important because it can support a Hatch-Waxman patent certification and, depending on the certification and litigation outcome, a statutory stay of FDA approval for an ANDA.

The patent is a method-of-use patent. A generic applicant may attempt to avoid infringement through:

• A Paragraph III certification agreeing to wait until patent expiration;
• A Paragraph IV certification challenging validity, enforceability, or infringement;
• A section viii statement carving out the patented method from the proposed labeling;
• A product and labeling strategy that does not encourage the claimed combination regimen.

A section viii carveout is difficult where the patented method corresponds closely to the principal FDA-approved use of the reference product. It becomes more viable where the patent covers only a specific chemotherapy setting, dosing schedule, or combination with dexamethasone.

FDA approval of a generic product is not itself a finding that the patent is invalid or not infringed. Orange Book listing and patent litigation are separate from FDA product-quality review. [1]

Are Paragraph IV challenges likely for this patent?

A Paragraph IV challenge would likely focus on four issues:

Obviousness

A challenger could combine prior-art teachings involving:

• Netupitant or another NK1 receptor antagonist;
• Palonosetron or another 5-HT3 receptor antagonist;
• Dexamethasone;
• Acute and delayed CINV prevention;
• Single-dose or long-acting antiemetic regimens.

The patent holder would rely on the claimed combination, long-duration NK1 receptor occupancy, reduced dexamethasone exposure, and clinical efficacy across both moderate and highly emetogenic chemotherapy.

The narrower claims covering the 300 mg/0.50 mg single-dose regimen may be more resilient if the record establishes unexpected efficacy, five-day protection, or clinically meaningful reduction in steroid exposure.

Indefiniteness

Potential targets include:

• "Sub-therapeutic dose";
• "Effective to treat said CINV";
• "Blood levels ... effective to treat";
• "Substantially absent";
• "At least 70% of said patient's striatum NK1 receptors."

The strongest indefiniteness argument would concern terms lacking a reproducible measurement method or a clear boundary. The receptor-occupancy claims are particularly dependent on the assay, imaging methodology, timing, and patient-specific measurement conditions.

Written description and enablement

The patent covers multiple routes, chemotherapy classes, dose schedules, pharmacodynamic outcomes, and treatment phases. A challenger could argue that the full breadth of claims exceeds the disclosed clinical evidence.

The patent owner would point to the detailed regimen examples and the pharmacological rationale for combining a long-acting NK1 antagonist with palonosetron and dexamethasone.

Infringement

Method claims require performance of the claimed steps. A generic manufacturer may avoid direct infringement if its label omits the patented regimen. The patent holder may still pursue induced infringement if the labeling, promotional materials, dosing instructions, or healthcare-provider communications encourage use of the patented method.

Which companies are challenging the Akynzeo patent estate?

Publicly available regulatory and litigation records should be reviewed for each ANDA applicant because the challenge landscape can change with new filings, settlements, and product launches. The relevant potential challengers are generic manufacturers with ANDAs for netupitant-palonosetron products, including large U.S. generic companies and specialty manufacturers.

The principal commercial barrier is that netupitant is not a widely substituted standalone generic ingredient. A challenger must develop:

• A bioequivalent fixed-dose combination;
• A formulation that meets FDA quality and dissolution requirements;
• A legally viable label;
• A strategy for the Orange Book-listed method claims;
• Sufficient supply and market access to compete with Akynzeo.

No biosimilar pathway applies. Netupitant and palonosetron are small molecules, so competition would proceed through the ANDA pathway rather than a 351(k) biologics application.

How does U.S. Patent 9,186,357 compare with other Akynzeo patents?

The Akynzeo estate includes distinct patent categories.

Patent category	Protected subject matter	Risk to generic entry
Composition patents	Netupitant-palonosetron combinations and pharmaceutical compositions	Direct product and formulation risk
Method patents	CINV treatment, dosing, timing, and chemotherapy-specific use	Label and induced-infringement risk
Formulation patents	Fixed-dose oral products, stability, release, and manufacturing characteristics	Product-development risk
Prodrug and intravenous patents	Fosnetupitant or intravenous netupitant delivery	Separate risk for IV products
Manufacturing patents	Preparation, purification, solid forms, salts, and impurity control	Supply-chain and process risk

U.S. Patent 9,186,357 is most significant as a regimen patent. It does not by itself prevent every netupitant-palonosetron product from entering the market. A generic could potentially avoid some claims by changing the dosage form, omitting dexamethasone from the label, using a different treatment indication, or launching after the relevant patent term. Those strategies may still face other Akynzeo patents.

What patent litigation affects netupitant and palonosetron?

The litigation exposure should be evaluated at the NDA and patent-family level rather than by patent number alone. The relevant litigation triggers are:

1. An ANDA applicant files a Paragraph IV certification;
2. The patent owner receives the statutory notice;
3. The patent owner files suit within the applicable 45-day period;
4. FDA approval is potentially stayed for up to 30 months, subject to statutory exceptions;
5. The parties settle, litigate to judgment, or agree to a licensed entry date.

A settlement may authorize an earlier generic launch without eliminating the patent. It may also include restrictions involving product formulation, labeling, supply, or authorized-generic rights. The commercial entry date in a settlement can therefore differ materially from the patent expiration date.

What generic entry risks exist?

Oral fixed-dose combination

The highest-risk target is a product that duplicates:

• 300 mg netupitant;
• 0.50 mg palonosetron hydrochloride;
• A single oral unit dosage form;
• Administration less than two hours before chemotherapy;
• Use with the claimed dexamethasone schedules;
• Five-day CINV prevention.

That product would face the greatest overlap with claims 19 through 23 and 33 through 39.

Netupitant with separate palonosetron

Separating the two active ingredients may avoid the single-unit limitation in claim 21, but it could remain within broader claims 1, 4, 18, or 19 depending on the precise regimen.

Netupitant without palonosetron

A netupitant-only product may avoid the palonosetron claims but could implicate claims 2, 11 through 13, 40 through 51, or 41 through 48 if it is labeled with the reduced-dose dexamethasone regimen.

Intravenous product

An IV product that produces effective blood levels of netupitant and palonosetron may face claims 4 and 53 through 62. Separate patents directed to fosnetupitant or IV delivery may create additional barriers.

How strong is the patent estate for U.S. Patent 9,186,357?

The patent has moderate-to-strong commercial value in the labeled Akynzeo regimen because the narrower claims track the product dose and clinical protocol closely. Its strength is lower against redesigned products that omit one active ingredient, use a separate dosage form, alter timing, or pursue a carved-out label.

Strength factor	Assessment
Product-regimen overlap	High for the labeled oral Akynzeo regimen
Breadth	High in claims 1, 2, and 4; narrower in claims 21-23
Evidence burden	Material for efficacy, receptor occupancy, and blood-level claims
Design-around potential	Moderate
Biosimilar exposure	None
Generic exposure	Material after Paragraph IV filing
Commercial duration	Protection expected into approximately 2029, subject to term records

The patent is strongest as part of a layered estate. A generic that defeats or avoids this method patent may still confront composition, formulation, IV, or manufacturing patents.

What is the competitive landscape for CINV prevention?

Akynzeo competes in a market that includes:

• Aprepitant and fosaprepitant products, including Emend;
• Palonosetron products, including Aloxi and generic palonosetron;
• Rolapitant, including Varubi where commercially available;
• Netupitant-palonosetron fixed-dose products;
• Olanzapine-containing antiemetic regimens;
• Dexamethasone-based combination protocols.

Akynzeo’s principal differentiation is prolonged NK1 activity combined with palonosetron in one oral dose. Generic palonosetron and aprepitant products create price pressure, but they do not automatically substitute for a netupitant-palonosetron product under the patented regimen.

Revenue exposure is concentrated in the netupitant-palonosetron franchise rather than in palonosetron alone. A successful generic launch could affect the entire fixed-dose combination price structure, particularly in oncology practices and hospital purchasing contracts.

Key Takeaways

• U.S. Patent 9,186,357 is a method-of-treatment patent covering netupitant-based CINV regimens.
• Claims 1, 2, and 4 establish the three main coverage categories: triple therapy, steroid-sparing therapy, and effective blood-level regimens.
• Claims 19 through 23 closely track the commercial Akynzeo oral regimen.
• Claims 22 and 23 cover dexamethasone schedules for moderately and highly emetogenic chemotherapy.
• The patent is expected to remain relevant through approximately September 2029, subject to the official USPTO term record.
• The patent does not eliminate all generic pathways because a challenger may pursue a Paragraph III certification, Paragraph IV litigation, section viii carveout, or non-infringing regimen.
• No biosimilar pathway applies because netupitant and palonosetron are small molecules.
• The patent’s practical strength depends on the broader Akynzeo composition, formulation, IV, and manufacturing estate.
• The highest infringement risk concerns a product duplicating the 300 mg netupitant/0.50 mg palonosetron single-dose regimen with the claimed dexamethasone schedules.

FAQs

Does U.S. Patent 9,186,357 claim Akynzeo itself?

No. It principally claims methods of using netupitant and palonosetron, with or without dexamethasone, to treat CINV. Other patents may claim the physical composition or formulation.

Can a generic launch before September 2029?

Yes, potentially through a successful patent challenge, a settlement license, an authorized-generic arrangement, or a product and label that avoid the enforceable claims. Patent expiration alone is not the only possible launch mechanism.

Does omitting dexamethasone avoid the patent?

It may avoid claims requiring dexamethasone, but claims directed to netupitant and palonosetron alone, including claims 4 and 18 through 39, may remain relevant.

Is the 70% NK1-receptor occupancy limitation easy to design around?

A product could attempt to avoid that limitation by producing a different pharmacodynamic profile. The practical result depends on whether broader claims are also infringed and whether the product’s clinical labeling encourages the claimed treatment method.

Does generic palonosetron create a direct substitute for Akynzeo?

No. Generic palonosetron supplies only the 5-HT3 antagonist component. Akynzeo combines palonosetron with netupitant, an NK1 antagonist designed to control delayed CINV.

References

1. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
2. U.S. Food and Drug Administration. (2024). Akynzeo prescribing information. Helsinn Healthcare SA.
3. U.S. Patent and Trademark Office. (2015). U.S. Patent No. 9,186,357: Methods for treating chemotherapy-induced nausea and vomiting.
4. U.S. Food and Drug Administration. (2024). Approved drug product list, NDA 205718: Akynzeo.
5. U.S. Food and Drug Administration. (2018). ANDA submissions: Refuse-to-receive standards.
6. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417.

Drugs Protected by US Patent 9,186,357

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Helsinn Hlthcare	AKYNZEO	netupitant; palonosetron hydrochloride	CAPSULE;ORAL	205718-001	Oct 10, 2014		RX	Yes	Yes						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF CANCER CHEMOTHERAPY, INCLUDING, BUT NOT LIMITED TO, HIGHLY EMETOGENIC CHEMOTHERAPY
Helsinn Hlthcare	AKYNZEO	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	POWDER;INTRAVENOUS	210493-001	Apr 19, 2018		DISCN	Yes	No						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY EMETOGENIC CANCER CHEMOTHERAPY
Helsinn Hlthcare	AKYNZEO	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	SOLUTION;INTRAVENOUS	210493-002	May 27, 2020		RX	Yes	Yes						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY EMETOGENIC CANCER CHEMOTHERAPY

International Family Members for US Patent 9,186,357

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3083
Australia	2010320598
Brazil	112012011485
Canada	2778301
Chile	2012001276
China	102655864