United States Patent 10,624,911: Fosnetupitant Injectable Formulation Claims and Patent Landscape

US 10,624,911 is directed to injectable fosnetupitant formulations containing palonosetron, an alkalizing agent, and defined pH and excipient ranges. The broadest commercial risk is concentrated in claims 19-21, which cover a stable liquid formulation with fosnetupitant, palonosetron, sodium hydroxide and an alkaline pH. Claims 1-18 provide narrower composition, lyophilization, reconstitution and manufacturing-process protection.

The patent is formulation-focused. It does not broadly claim fosnetupitant as a chemical compound or every therapeutic use of the active ingredient. A competing product may avoid infringement by changing the salt form, removing palonosetron, using a non-alkaline formulation, substituting excipients, or adopting a materially different manufacturing process. Those design-around routes may be constrained if other patents cover fosnetupitant, palonosetron combinations, approved dosage forms or manufacturing intermediates.

What does US Patent 10,624,911 protect?

The patent claims two principal product categories:

A liquid injectable fosnetupitant formulation.
A lyophilized fosnetupitant formulation reconstituted before injection.

The claims require fosnetupitant in a specified salt form, the chloride hydrochloride salt, together with palonosetron hydrochloride. Most claims also require mannitol, disodium edetate and sodium hydroxide, with hydrochloric acid permitted for pH adjustment.

Claim group	Subject matter	Principal limitations
Claims 1, 3, 9-11, 14, 19-21	Liquid injectable formulations	Fosnetupitant, palonosetron, alkaline pH or sodium hydroxide; several claims require mannitol and edetate
Claims 2, 4-6, 12-13, 15-17	Lyophilized formulations	Same active ingredients and excipient ranges, assessed after reconstitution
Claims 7 and 18	Manufacturing process	High-pH mixing with sodium hydroxide followed by pH reduction using an acid
Claim 8	Diluted intravenous product	Mixing the formulation with 0.9% saline or 5% glucose

The claims are cumulative. Independent claims 1-4 and 19 define different formulations, while dependent claims narrow concentration, pH, excipient and reconstitution parameters.

What active ingredients and excipients are required?

Fosnetupitant salt form

The claims require the chloride hydrochloride salt of fosnetupitant. This limitation is material. A formulation using a different fosnetupitant salt, a free base, or a chemically distinct prodrug may fall outside the literal scope of the claims, subject to claim-construction and equivalents issues.

The concentration range is generally 2.3 to 30 mg/mL. The preferred embodiment is approximately 13.0 mg/mL.

Palonosetron

Palonosetron hydrochloride is required at 5 to 50 micrograms per milliliter, with some claims specifying calculation based on palonosetron free base and others referring to the salt weight.

This limitation narrows the patent materially. A fosnetupitant injectable formulation without palonosetron would not satisfy the express combination requirement. A formulation using a different 5-HT3 antagonist would also avoid literal infringement of these claims.

Sodium hydroxide and alkaline pH

Sodium hydroxide is required in many claims. Claims 19-21 are broader in functional structure because they focus on an alkalizing agent and alkaline pH. Claim 20 narrows the alkalizing agent to sodium hydroxide and the pH to 7-10. Claim 21 similarly requires sodium hydroxide and a pH of 7-10.

The alkaline-pH limitation is commercially important because it may capture a product even if the formulation uses fewer excipients than the formulations in claims 1-18.

Disodium edetate

Disodium edetate, or EDTA, is required in claims 1, 3, 4, 6, 10-13 and related dependent claims. The liquid formulation range is 0.05 to 0.9 mg/mL in claim 3 and 0.1 to 2.0 mg/mL in narrower claims. The lyophilized formulations use 0.1 to 2.0 mg/mL based on reconstitution.

The preferred concentration is approximately 0.32 mg/mL.

Mannitol

Mannitol is required in claims 1-6 and 10-13. The claimed range is 10 to 100 mg/mL, with approximately 38 mg/mL identified as the preferred concentration.

Mannitol likely operates as a bulking or tonicity-adjusting agent in the lyophilized product and may also contribute to formulation stability and injectability.

How broad are the independent formulation claims?

Claim 1: broad liquid and lyophilized composition framework

Claim 1 covers a pharmaceutically stable injectable liquid formulation containing:

2.3-30 mg/mL fosnetupitant chloride hydrochloride;
5-50 micrograms/mL palonosetron hydrochloride;
sodium hydroxide;
disodium edetate;
optional hydrochloric acid; and
mannitol.

Although claim 1 is directed to a liquid formulation, it does not specify a pH range. It also does not expressly impose the narrower EDTA and mannitol ranges later recited in claim 3.

Claim 2: lyophilized counterpart

Claim 2 applies the same ingredient framework to a stable injectable lyophilized formulation. The claim is relevant to a product supplied as a powder or cake that is reconstituted before administration.

The distinction between a liquid and a lyophilized formulation is substantive. A generic sponsor would need to assess both the product supplied by the manufacturer and the reconstituted preparation used clinically.

Claims 3 and 4: range-defined formulations

Claims 3 and 4 add:

pH 7.0-10.0;
EDTA concentration limits;
mannitol concentration limits;
water q.s. for the liquid formulation; and
reconstitution-based measurements for the lyophilized product.

These claims create a more technically defined infringement test. A formulation outside any one required concentration range may avoid literal infringement, but the commercial value of such a design-around depends on whether stability, compatibility and manufacturing constraints permit the change.

Claims 19-21: simplified alkaline liquid claims

Claims 19-21 are among the most commercially significant claims.

Claim 19 requires:

fosnetupitant chloride hydrochloride;
palonosetron hydrochloride;
an alkalizing agent; and
an alkaline pH.

It does not expressly require mannitol or EDTA. Claim 20 narrows the claim to approximately 13.0 mg/mL fosnetupitant, approximately 14.04 micrograms/mL palonosetron, sodium hydroxide and pH 7-10. Claim 21 requires sodium hydroxide and pH 7-10 but retains the broader concentration ranges of claim 19.

These claims may reach a simplified liquid formulation that omits one or more excipients recited in the earlier claims.

Which claims cover the commercial-strength formulation?

The preferred formulation is repeated in claims 6, 11 and 13:

Parameter	Claimed preferred value
Fosnetupitant chloride hydrochloride	Approximately 13.0 mg/mL
Palonosetron hydrochloride	Approximately 14.04 micrograms/mL
Disodium edetate	Approximately 0.32 mg/mL
Mannitol	Approximately 38 mg/mL
pH	8.5-9.5
Reconstitution volume	20 mL for claim 6

Claims 6 and 13 target the lyophilized product. Claim 11 targets the liquid product. The use of “about” creates an issue of claim construction. Courts generally assess whether a competing concentration falls within the scope of the approximation in view of the specification, prosecution history and technical tolerance.

A product matching these values presents the highest literal infringement risk.

What manufacturing process is protected?

Claims 7 and 18

Claim 7 covers a process with three central steps:

Simultaneously mixing fosnetupitant chloride hydrochloride and sodium hydroxide in water at pH approximately 11-14.
Reducing the pH to approximately 7-10 by adding one or more acidic pH-adjusting agents.
Optionally adding pharmaceutically acceptable excipients.

Claim 18 specifies hydrochloric acid as the acidic pH-adjusting agent.

The process claims are narrower than the composition claims because infringement depends on how the formulation is made. A manufacturer using a different order of addition, a lower initial pH, a different acid, or a premixed buffer system may have a noninfringement position. Process discovery can be difficult, particularly where manufacturing records are not publicly available. A generic applicant may need to provide a detailed paragraph IV certification and supporting noninfringement statement.

Does claim 8 cover administration after dilution?

Claim 8 covers an intravenous formulation made by mixing the formulation of claim 2 with either:

0.9% saline; or
5% glucose.

This claim is directed to the diluted administration preparation rather than only the vial contents. It may capture the hospital-use configuration if the lyophilized fosnetupitant/palonosetron product is reconstituted or further diluted in one of the specified solutions.

The claim does not expressly cover every diluent. Use of another compatible diluent would require separate analysis.

What are the principal infringement tests?

A competing product presents elevated risk if it has all or substantially all of the following:

fosnetupitant chloride hydrochloride;
palonosetron hydrochloride;
sodium hydroxide or another alkalizing agent;
pH between 7 and 10;
approximately 13 mg/mL fosnetupitant;
approximately 14.04 micrograms/mL palonosetron;
EDTA near 0.32 mg/mL;
mannitol near 38 mg/mL; and
liquid or lyophilized injectable presentation.

Competing product characteristic	Likely US 10,624,911 exposure
Same actives, alkaline liquid, sodium hydroxide	High, particularly claims 19-21
Same actives, mannitol and EDTA, pH 7-10	High, claims 1-6 and 10-13
Same actives but neutral or acidic pH	Lower under alkaline-pH claims; other claims require analysis
Fosnetupitant without palonosetron	Low under the supplied claims
Palonosetron without fosnetupitant	No infringement of the supplied claims
Different fosnetupitant salt	Potential design-around
Same formulation but different manufacturing sequence	Composition claims remain relevant; process claims may be avoided
Same lyophilized cake, different reconstitution volume	May affect range-based claims, but not necessarily all composition claims
Same formula diluted in saline or glucose	Potential claim 8 exposure

What validity issues could affect the patent?

The most relevant validity issues are likely to involve:

Anticipation

A single prior-art reference would need to disclose every limitation of the asserted claim, including the specific fosnetupitant salt, palonosetron concentration, pH, excipient combination and stability requirement. Broad claims 19 and 21 may face a broader prior-art search than the narrowly quantified claims.

Obviousness

Potential obviousness arguments may combine:

known fosnetupitant formulations;
palonosetron-containing antiemetic products;
alkaline pH adjustment;
EDTA as a chelator;
mannitol as a bulking or tonicity agent; and
conventional lyophilization techniques.

The patentee’s strongest response would likely rely on unexpected stability, compatibility, reduced degradation, improved reconstitution or manufacturing advantages. Those issues depend on the patent specification and prosecution record, not the issued claims alone.

Written description and enablement

The broad ranges, especially 2.3-30 mg/mL fosnetupitant and 5-50 micrograms/mL palonosetron, could be tested against the amount of experimental support in the specification. The same applies to the broad alkaline pH formulation in claim 19.

Indefiniteness

Potential disputes may concern:

“pharmaceutically stable”;
“about”;
“alkaline pH”;
“suitable water volume”; and
concentration measured on a free-base or salt basis.

These terms may be construed using the specification, analytical methods and prosecution history.

When does US 10,624,911 lose exclusivity?

The patent’s enforceable term cannot be determined from the claims alone. The relevant date is the earliest effective nonprovisional or international application filing date, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension. FDA regulatory exclusivity is separate from patent exclusivity.

The patent was issued in 2020, but patent expiration is not calculated from the issue date. A nominal expiration analysis requires the complete priority chain and USPTO term calculation. Any Orange Book listing would also need to be checked against the FDA’s current publication and patent-use-code records. [1][2]

What is the Orange Book and FDA status?

US 10,624,911 is a patent-rights question separate from FDA approval. The FDA Orange Book may list patents for an approved drug product only if the sponsor submitted the patent information and the FDA accepted it under applicable listing rules. An Orange Book listing does not itself establish validity or infringement.

The relevant regulatory product is the fosnetupitant/palonosetron injectable combination associated with the Akynzeo product family. The FDA-approved label controls the approved dosage form, administration route, preparation instructions and diluents. [3]

The claim text does not establish:

whether US 10,624,911 is currently listed in the Orange Book;
the applicable patent-use code;
whether a generic application has been filed;
whether a paragraph IV certification has been served;
whether litigation has commenced; or
whether a settlement agreement exists.

Those matters are determined from FDA listing records, ANDA litigation dockets and settlement disclosures, not from the issued claims.

Are biosimilars a risk for fosnetupitant?

No biosimilar pathway applies to fosnetupitant because it is a small-molecule drug. Competitive entry would proceed through the abbreviated new drug application pathway or another small-molecule regulatory route, not under the Public Health Service Act biosimilar framework.

The relevant commercial risks are:

ANDA filing;
paragraph III certification;
paragraph IV invalidity or noninfringement challenge;
formulation substitution;
alternate salt or dosage form development; and
post-patent generic launch.

Which design-arounds are most credible?

A generic or competing manufacturer could examine:

A formulation without palonosetron.
A different antiemetic combination.
A different fosnetupitant salt or chemical form.
A pH below 7 or outside the claimed alkaline ranges.
Replacement of sodium hydroxide with another alkalizing system.
Removal or substitution of EDTA.
Replacement of mannitol.
A liquid product rather than a lyophilized product, or vice versa.
A different reconstitution volume.
A different order of addition and pH-adjustment process.

The first five routes offer the clearest opportunities against the supplied claims. The formulation must still meet stability, sterility, compatibility, toxicity and regulatory requirements.

How strong is the patent estate based on the supplied claims?

The patent has meaningful commercial coverage because it combines composition claims with process and administration claims. Its strongest features are:

coverage of both liquid and lyophilized presentations;
a broad alkaline liquid formulation in claim 19;
a sodium-hydroxide-specific claim in claim 21;
preferred commercial-strength concentrations;
manufacturing-process coverage; and
dilution in common intravenous carriers.

Its principal limitations are:

dependence on the fosnetupitant/palonosetron combination;
dependence on a specified fosnetupitant salt;
extensive excipient and pH limitations in many claims;
potential design-around options involving salt, pH and excipient selection; and
the need to establish live patent term, listing status and prosecution history before assessing enforcement value.

Key Takeaways

US 10,624,911 is a formulation and manufacturing patent, not a broad compound patent.
Claims 19-21 create the broadest liquid-formulation risk because they require fosnetupitant, palonosetron, an alkalizing agent and an alkaline pH without requiring all excipients.
Claims 6, 11 and 13 target the preferred formulation containing approximately 13 mg/mL fosnetupitant, 14.04 micrograms/mL palonosetron, 0.32 mg/mL EDTA and 38 mg/mL mannitol.
Claims 7 and 18 protect a high-pH mixing process followed by acidification.
Claim 8 reaches dilution with saline or 5% glucose.
The most credible design-arounds involve a different salt form, removal of palonosetron, non-alkaline pH, excipient substitution or a different manufacturing sequence.
Fosnetupitant is a small molecule, so biosimilar exposure does not apply.
Orange Book listing, patent expiration, paragraph IV activity, litigation and settlements require separate FDA, USPTO and court-record verification.

FAQs About US Patent 10,624,911

Does US 10,624,911 cover oral fosnetupitant products?

No. The supplied claims are directed to injectable liquid, lyophilized and diluted intravenous formulations. They do not claim an oral dosage form.

Does the patent require both fosnetupitant and palonosetron?

Yes. Every supplied independent formulation claim requires fosnetupitant and palonosetron hydrochloride.

Can a formulation using a different alkalizing agent avoid the patent?

It may avoid claims specifically requiring sodium hydroxide, but claim 19 uses the broader term “an alkalizing agent.” The full formulation and claim construction must be evaluated.

Does a pH of exactly 7 satisfy the pH claims?

Claims 3 and 4 recite pH 7.0-10.0, and claims 20 and 21 recite pH from 7 to 10. A pH of exactly 7 is within those literal numerical ranges, subject to measurement and claim-construction issues.

Is a product infringing if it contains the same ingredients but is made by a different process?

Potentially yes. Product claims are assessed independently of the manufacturing-process claims. A different manufacturing method may avoid claims 7 and 18 but will not avoid an otherwise applicable composition claim.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,624,911.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Akynzeo (fosnetupitant/palonosetron) prescribing information.

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	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	POWDER;INTRAVENOUS	210493-001	Apr 19, 2018		DISCN	Yes	No	10,624,911	⤷ Start Trial	Y				⤷ Start Trial
Helsinn Hlthcare	AKYNZEO	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	SOLUTION;INTRAVENOUS	210493-002	May 27, 2020		RX	Yes	Yes	10,624,911	⤷ 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	108676	⤷ Start Trial
Australia	2017276588	⤷ Start Trial
Brazil	112018074655	⤷ Start Trial
Canada	3025837	⤷ Start Trial
Chile	2018003338	⤷ Start Trial
China	109310627	⤷ Start Trial
Colombia	2018011686	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,624,911