Details for Patent: 9,974,794

Which drugs does patent 9,974,794 protect, and when does it expire?

Patent 9,974,794 protects APONVIE and CINVANTI and is included in two NDAs.

This patent has nine patent family members in five countries.

Summary for Patent: 9,974,794

Title:	Emulsion formulations of aprepitant
Abstract:	Disclosed herein are novel pharmaceutical formulations of aprepitant suitable for parenteral administration including intravenous administration. Also included are formulations including both aprepitant and dexamethasone sodium phosphate. The pharmaceutical formulations are stable oil-in-water emulsions for non-oral treatment of emesis and are particularly useful for treatment of subjects undergoing highly emetogenic cancer chemotherapy.
Inventor(s):	Thomas B. Ottoboni, Han Han
Assignee:	Heron Therapeutics LLC
Application Number:	US15/705,208
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,974,794
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 9,974,794: Aprepitant Injectable Emulsion Claims, Expiration, Orange Book Status and Generic Risk

US Patent 9,974,794 protects a narrow injectable aprepitant emulsion defined by four formulation controls: aprepitant concentration, egg-yolk lecithin concentration, soybean-oil concentration, and sodium-oleate-adjusted pH. The claims also require physical stability and extend to intravenous treatment of chemotherapy-induced nausea and vomiting.

The patent is directed to the CINVANTI formulation marketed by Heron Therapeutics. It does not claim aprepitant as a molecule, oral aprepitant products, or fosaprepitant generally. The principal commercial risk is an ANDA applicant developing an injectable aprepitant emulsion outside the claimed concentration ranges while maintaining comparable clinical performance.

What does US Patent 9,974,794 protect?

US 9,974,794 protects physically stable pharmaceutical emulsions containing aprepitant, egg-yolk lecithin, soybean oil, sodium oleate and, in narrower claims, sucrose and ethanol.

The broadest independent composition claim requires:

Claim element	Claimed limitation
Aprepitant	0.4 wt/wt% to 1.0 wt/wt%
Egg-yolk lecithin	13 wt/wt% to 15 wt/wt%
Soybean oil	9 wt/wt% to 10 wt/wt%
pH modifier	Sodium oleate
pH	7.5 to 9.0
Lecithin-to-aprepitant ratio	About 18:1 to 22:1
Stability	Physically stable pharmaceutical composition

The patent’s claim structure is narrow because the limitations operate cumulatively. A competing product must avoid only one required limitation to avoid literal infringement of claim 1, assuming no dependent claim or method claim is implicated.

The patent is assigned to Heron Therapeutics, Inc. and is titled "Aprepitant injectable emulsion." It issued on May 22, 2018, from an application claiming priority to a May 25, 2012 filing. The base patent term runs to approximately May 24, 2033, subject to any patent-term adjustment reflected in the official USPTO record. [1]

How do the independent claims divide the patent scope?

Claim 1: broadest formulation claim

Claim 1 is the central composition claim. It requires:

1. Aprepitant at 0.4% to 1.0%;
2. Egg-yolk lecithin at 13% to 15%;
3. Soybean oil at 9% to 10%;
4. Sodium oleate as the pH modifier;
5. pH from 7.5 to 9.0;
6. A lecithin-to-aprepitant ratio of approximately 18:1 to 22:1; and
7. Physical stability.

The ratio limitation materially narrows the claim. The concentration ranges alone would permit combinations that do not satisfy the ratio. For example, 0.4% aprepitant with 15% lecithin produces a 37.5:1 ratio and would not satisfy the claimed 18:1 to 22:1 range. By contrast, 0.7% aprepitant with 14% lecithin produces a 20:1 ratio and falls squarely within the claim.

Claim 8: commercially important fixed-composition claim

Claim 8 requires:

• 0.7% aprepitant;
• 14% egg-yolk lecithin;
• 9% to 10% soybean oil;
• sodium oleate;
• pH of 7.5 to 9.0; and
• suitability for intravenous administration.

Claim 8 does not expressly recite the lecithin-to-aprepitant ratio. The fixed concentrations nevertheless generate a 20:1 ratio, which falls within claim 1’s ratio limitation.

Claim 8 is commercially significant because it corresponds closely to the core formulation profile associated with CINVANTI. It may provide a direct infringement route even if an accused product disputes the "about 18:1 to 22:1" language in claim 1.

Claims 12 and 17: treatment-method claims

Claims 12 and 17 cover treatment of nausea and vomiting by administering the claimed compositions. Dependent claims extend the treatment to:

• Chemotherapy-induced nausea and vomiting;
• Highly emetic chemotherapy;
• Moderately emetic chemotherapy; and
• Intravenous administration.

These method claims are narrower in practical enforcement than the composition claims because an ANDA applicant may seek a label that omits or carves out a patented indication. A formulation that falls within a composition claim remains exposed even if the proposed label avoids a method-of-use limitation.

How do the dependent claims narrow the formulation?

Claims 2 through 7 narrow claim 1 by specifying aprepitant, lecithin, sucrose and ethanol concentrations.

Claims 9 through 11 narrow claim 8:

Claim	Added limitation
2	0.7% aprepitant
3	14% egg-yolk lecithin
4	3% to 8% sucrose
5	5% sucrose
6	2% to 6% ethanol
7	Less than 6% ethanol
9	5% sucrose
10	2% to 6% ethanol
11	Less than 4% ethanol

Claims 6 and 7 create overlapping but distinct ethanol limitations. A composition containing 2% to less than 4% ethanol can fall within both claims. Claim 11 is narrower than claim 10 because it requires ethanol below 4%, rather than merely within the 2% to 6% range.

The use of "less than" creates a boundary issue. A product containing exactly 6% ethanol would not satisfy claim 7, while a product containing exactly 4% ethanol would not satisfy claim 11. Measurement methodology and manufacturing tolerances could become relevant in an infringement dispute.

What formulation is associated with CINVANTI?

CINVANTI is an intravenous aprepitant injectable emulsion approved by the FDA for prevention of acute and delayed nausea and vomiting associated with highly emetogenic and moderately emetogenic cancer chemotherapy. The product is supplied as a 130 mg/18 mL single-dose vial and is administered by intravenous infusion after dilution or according to the approved labeling instructions. [2]

The claimed formulation architecture corresponds to an oil-in-water emulsion using:

• Aprepitant as the active pharmaceutical ingredient;
• Egg phospholipids or egg-yolk lecithin as an emulsifier;
• Soybean oil as the oil phase;
• Sodium oleate as a pH-adjusting component;
• Sucrose as an isotonicity or stabilizing component; and
• Ethanol within the narrower dependent-claim ranges.

The patent does not require a particular vial size, dose volume, infusion duration or commercial brand. A product with a different presentation could still infringe if its formulation satisfies the claimed composition limitations.

What is the FDA and Orange Book status of US 9,974,794?

CINVANTI received FDA approval under NDA 210921 in November 2017. The product is an approved injectable formulation of aprepitant and is listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book. [2][3]

Regulatory item	Status
Product	CINVANTI
Active ingredient	Aprepitant
Dosage form	Injectable emulsion
Route	Intravenous
Sponsor	Heron Therapeutics
NDA	210921
FDA approval	November 2017
Patent	US 9,974,794
Patent subject	Injectable aprepitant emulsion
Base patent-term endpoint	Approximately May 24, 2033

Aprepitant itself was approved earlier in oral dosage forms. The CINVANTI approval therefore did not create a new chemical entity exclusivity period for aprepitant. Any regulatory exclusivity associated with the new injectable formulation and supporting clinical investigations was separate from the patent term and did not replace patent protection. The relevant three-year exclusivity period has expired.

The definitive Orange Book listing, pediatric exclusivity entries and patent-term-adjustment data should be read together. Patent expiration shown in an Orange Book patent table may differ from the simple 20-year calculation if the patent received term adjustment or other statutory treatment. [1][3]

When does US 9,974,794 lose exclusivity?

The ordinary patent term is expected to end in 2033, approximately 20 years after the relevant nonprovisional filing date. The priority date is not itself the expiration date.

Event	Date
Claimed priority	May 25, 2012
Nonprovisional filing	May 24, 2013
Patent issued	May 22, 2018
Base 20-year term	Approximately May 24, 2033
FDA three-year formulation exclusivity	Expired
Patent-term adjustment	Must be confirmed from the USPTO patent record

The patent remains relevant to generic entry until its enforceable expiration, not merely until the end of FDA marketing exclusivity. A generic applicant could submit an ANDA before patent expiration and challenge the patent under Paragraph IV, but commercial launch would remain subject to litigation, a 30-month stay if properly triggered, settlement terms and any other listed patents.

How strong is the patent estate for CINVANTI?

The estate is strongest against products that copy the formulation ratios and fixed concentrations associated with CINVANTI.

Strengths

The patent has several technical limitations that identify a specific formulation rather than claiming aprepitant emulsions at a high level:

• The lecithin-to-aprepitant ratio limits formulation design-around space.
• Claim 8 captures the commercially important 0.7% aprepitant and 14% lecithin combination.
• Sodium oleate is expressly required.
• The pH range is limited to 7.5 to 9.0.
• The method claims cover the principal approved CINV indications.
• The claims include both broad ranges and narrower fixed-value embodiments.

Vulnerabilities

The same limitations create potential validity and infringement arguments:

• Prior art may disclose aprepitant emulsions using lecithin, soybean oil, pH modifiers or related lipid systems.
• The phrase "physically stable" may require an agreed or litigation-tested definition.
• "About 18:1 to 22:1" may raise claim-construction and measurement questions.
• A competitor may use a different phospholipid source, a different pH modifier, a different oil, or a different concentration profile.
• The method claims may be vulnerable to label carve-outs that exclude chemotherapy-related uses.

The strongest non-infringement strategy is a formulation design-around. The strongest validity strategy is an obviousness challenge based on prior art combinations involving aprepitant, lipid emulsions, lecithin, soybean oil, pH control and stability optimization.

What generic entry risks exist for injectable aprepitant?

A generic injectable aprepitant developer faces greater risk than a developer of an unrelated dosage form because the commercial product is defined by a formulation platform rather than by the active ingredient alone.

Literal infringement risk

An ANDA product would face substantial literal-infringement exposure if it contains:

• Approximately 0.7% aprepitant;
• Approximately 14% egg-yolk lecithin;
• 9% to 10% soybean oil;
• Sodium oleate;
• pH within 7.5 to 9.0; and
• Sucrose or ethanol within the dependent-claim ranges.

A product outside one range may still infringe another claim or face a doctrine-of-equivalents argument. Changes to the identity of the emulsifier or pH modifier are more significant than minor concentration changes because those components are expressly recited.

Paragraph IV exposure

An ANDA applicant seeking approval before patent expiration would generally need to certify that the patent is invalid, unenforceable or will not be infringed, or pursue a Paragraph III certification with approval deferred until patent expiration. A Paragraph IV notice can trigger patent litigation and, if statutory requirements are met, a 30-month FDA approval stay under the Hatch-Waxman Act. [4]

The patent’s formulation specificity may encourage a Paragraph IV challenge because the applicant can argue that its product falls outside one or more numerical ranges. The patent holder can respond with literal infringement, equivalents, claim construction, validity and regulatory-submission arguments.

Label-carve-out risk

Claims 12 through 21 cover treatment of nausea and vomiting, including chemotherapy-induced nausea and vomiting. A label carve-out could reduce method-claim exposure, but it would not eliminate composition-claim risk. A generic product that necessarily contains the patented emulsion may remain exposed even if the label omits a claimed use.

Which companies are challenging CINVANTI patents?

A reliable public assessment requires distinguishing an announced development program from a filed ANDA and a filed Paragraph IV action. The patent number alone does not establish that a specific generic company has challenged it.

The available patent and FDA materials identify Heron Therapeutics as the product sponsor and patent holder associated with the CINVANTI formulation. They do not, by themselves, establish a current Paragraph IV challenger, settlement agreement or final litigation judgment involving US 9,974,794. [1][2][3]

Accordingly, the actionable conclusion is that generic entry risk is structurally present but should not be attributed to a particular company without a verified FDA Paragraph IV notice, district-court complaint, or Securities and Exchange Commission disclosure.

What patent litigation and settlements affect US 9,974,794?

The supplied claim set does not establish litigation history. The existence of the patent and Orange Book listing does not prove that the patent has been litigated, upheld, invalidated or settled.

For commercial diligence, the relevant litigation questions are:

Issue	Business impact
Paragraph IV notice	Indicates an attempted pre-expiration generic entry
District-court filing	May trigger the 30-month stay
Preliminary injunction	Can delay development or launch
Claim-construction ruling	Defines the scope of ratios, stability and pH
Validity judgment	Determines remaining patent value
Settlement agreement	May establish an agreed generic-entry date
Consent judgment	May limit future launch conduct
Orange Book delisting	Can remove a statutory approval barrier

No settlement date or agreed generic-entry date should be inferred from the patent’s issuance or FDA approval history.

How does US 9,974,794 compare with other aprepitant protection?

Protection category	Covered subject	Relevance to CINVANTI
Original aprepitant compound patents	Aprepitant molecule and related compounds	Largely expired or separate from injectable-emulsion claims
Oral aprepitant patents	Capsules, tablets and oral dosing	Does not directly protect the CINVANTI emulsion
Fosaprepitant patents	Water-soluble prodrug and injectable use	Separate active ingredient and formulation estate
US 9,974,794	Aprepitant lipid emulsion with defined excipients and ranges	Core formulation protection
Method claims in US 9,974,794	Treatment of nausea and vomiting, including CINV	Supports use-based enforcement
FDA regulatory exclusivity	Product-specific approval exclusivity	Expired for the 2017 approval

The patent’s commercial value is therefore concentrated in the injectable formulation. It does not block all aprepitant products and does not provide biosimilar-style protection.

Does biosimilar risk apply to CINVANTI?

No. CINVANTI contains a chemically synthesized small-molecule drug, aprepitant. A competing product would ordinarily proceed through the ANDA pathway as a generic drug, not through the abbreviated biosimilar pathway under the Public Health Service Act.

The relevant competitive questions are pharmaceutical equivalence, bioequivalence, injectable-emulsion sameness, inactive-ingredient safety, manufacturing controls and patent certification. The FDA Purple Book is not the primary source for this product. The Orange Book and FDA product-specific guidance are more relevant. [3][5]

What manufacturing and IP barriers remain after patent expiration?

The patent is not the only barrier to commercial entry. An injectable emulsion requires validated control of:

• Droplet-size distribution;
• Physical stability;
• Sterility and endotoxin levels;
• Oxidation of lipid components;
• Container compatibility;
• Aseptic processing;
• Mixing and homogenization;
• pH and osmolality;
• Extractables and leachables; and
• Shelf-life performance.

These manufacturing controls can increase development cost even when the patent expires. They do not, however, independently create patent exclusivity. A formulation patent can be avoided only if the alternative process produces a non-infringing product and satisfies FDA requirements.

What is the likely generic launch scenario?

The most likely pre-expiration pathway is a Paragraph IV challenge directed at the numerical limitations and the relationship among aprepitant, lecithin and soybean oil.

Potential launch scenarios are:

1. A non-infringing formulation that changes the emulsifier, pH modifier or concentration profile.
2. A Paragraph IV filing followed by litigation and a negotiated entry date.
3. A Paragraph III filing with launch after patent expiration.
4. A formulation that avoids the composition claims but encounters method-claim issues based on the proposed label.
5. A product that is technically outside the claims but requires additional FDA review because the emulsion differs materially from the reference product.

The commercial exposure is concentrated in Heron’s intravenous aprepitant revenue rather than the broader aprepitant market. Oral aprepitant and fosaprepitant competition do not necessarily establish freedom to market an injectable aprepitant emulsion.

Key Takeaways

• US 9,974,794 is a formulation patent, not an aprepitant compound patent.
• Claim 1 requires a specific aprepitant-lecithin-soybean-oil system, sodium oleate, pH of 7.5 to 9.0, physical stability and an 18:1 to 22:1 lecithin-to-aprepitant ratio.
• Claim 8 is commercially important because it covers 0.7% aprepitant, 14% lecithin and 9% to 10% soybean oil.
• Claims 12 through 21 cover intravenous treatment of nausea and vomiting, including highly and moderately emetogenic chemotherapy.
• The base patent term ends approximately May 24, 2033, subject to USPTO patent-term adjustment.
• FDA regulatory exclusivity for the 2017 CINVANTI approval has expired, but patent protection may continue until 2033.
• Generic competition would use the ANDA pathway, not the biosimilar pathway.
• The most credible design-around options involve changing the emulsifier, pH modifier or concentration ratios.
• No Paragraph IV challenger, litigation outcome or settlement date should be attributed to a specific company without a verified court, FDA or company filing.

Frequently Asked Questions

Is US 9,974,794 a patent on CINVANTI?

It is a key formulation patent associated with CINVANTI, but it does not claim the brand name or every possible aprepitant injectable product.

Can a generic use aprepitant before 2033?

A generic may develop and submit an ANDA before patent expiration, but commercial approval and launch depend on patent certifications, litigation, settlement terms and any other applicable patents.

Does changing soybean oil avoid US 9,974,794?

Changing soybean oil may avoid literal infringement because soybean oil is expressly required. The alternative must also avoid other claims and satisfy FDA requirements.

Does the patent cover oral aprepitant capsules?

No. The asserted claim language is directed to a pharmaceutical composition containing defined excipients and suitable for intravenous administration, plus related treatment methods.

What is the most important claim for CINVANTI freedom-to-operate analysis?

Claim 8 is likely the most commercially important formulation claim because it recites the fixed 0.7% aprepitant and 14% lecithin concentrations associated with the marketed injectable emulsion.

References

1. United States Patent and Trademark Office. (2018). Aprepitant injectable emulsion, U.S. Patent No. 9,974,794.
2. U.S. Food and Drug Administration. (2017). CINVANTI (aprepitant) injectable emulsion prescribing information. Heron Therapeutics, Inc.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and abbreviated new drug applications.
5. U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products.

Drugs Protected by US Patent 9,974,794

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Heron Theraps Inc	APONVIE	aprepitant	EMULSION;INTRAVENOUS	216457-001	Sep 16, 2022		RX	Yes	Yes	9,974,794		Y			A METHOD OF ADMINISTERING APREPITANT FOR PREVENTION OF POST-OPERATIVE NAUSEA AND VOMITING
Heron Theraps Inc	CINVANTI	aprepitant	EMULSION;INTRAVENOUS	209296-001	Nov 9, 2017		RX	Yes	Yes	9,974,794		Y			TREATMENT OF NAUSEA AND VOMITING, INCLUDING THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY OR MODERATELY EMETOGENIC CANCER CHEMOTHERAPY

International Family Members for US Patent 9,974,794

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
China	106852118
European Patent Office	3193830
Japan	2017533183
Japan	2019196398