US Patent 9,833,459: Fulvestrant Formulation Claims, Patent Scope, and Generic Entry Risk

US Patent No. 9,833,459 protects a specific fulvestrant injectable formulation built around castor oil, alcohols, a nonionic surfactant, and an antioxidant, while excluding a non-aqueous ester solvent. The broadest independent composition claim is narrow in chemical architecture but potentially significant for injectable fulvestrant products that replace benzyl benzoate or another ester solvent with a low-impurity ricinoleate vehicle.

The patent also covers defined impurity-performance thresholds, prefilled syringes, vials, and treatment of hormone receptor-positive metastatic breast cancer. It does not broadly cover every fulvestrant product, every castor-oil formulation, or the fulvestrant molecule itself.

What does US Patent 9,833,459 cover?

The patent covers five related subject-matter categories:

Category	Claims	Protected subject matter
Core composition	1-12	Fulvestrant with alcohol, nonionic surfactant, antioxidant, and ricinoleate vehicle, substantially free of a non-aqueous ester solvent
Specific excipients	3-10	Polysorbate 80, castor oil, vitamin E compounds, alpha-tocopherol, ethanol, benzyl alcohol, and castor-oil quality parameters
Stability profile	11-12	Total impurities of no more than 1% and fulvestrant sulfone of no more than 0.5% after three months at 25°C
Drug-delivery containers	13-14	Syringes and vials containing 2.5 mL to 5 mL of the composition
Therapeutic use	15	Treatment of hormone receptor-positive metastatic breast cancer using the claimed composition

The patent is therefore a formulation and product patent, with additional claims directed to packaging and method of treatment. It is not a basic compound patent for fulvestrant.

How broad is claim 1 of US 9,833,459?

Claim 1 is the principal composition claim. A product must contain all of the following elements:

Fulvestrant.
A pharmaceutically acceptable alcohol.
A nonionic surfactant.
An antioxidant.
A ricinoleate vehicle.
A formulation that is substantially free of a non-aqueous ester solvent.

The claim is open-ended because it uses "comprising." A composition may contain additional excipients and still fall within claim 1, provided it contains the required components and satisfies the ester-solvent limitation.

The claim does not require:

A particular fulvestrant concentration.
A particular injection volume.
A particular dose.
A particular route of administration, although the product context is injectable.
Castor oil specifically.
Polysorbate 80 specifically.
Alpha-tocopherol specifically.
Ethanol and benzyl alcohol together.
The numerical impurity limits in claims 11 and 12.

Those narrower features appear in dependent claims.

What does "substantially free of a non-aqueous ester solvent" mean?

This is the most important scope limitation in claim 1. It is designed to exclude formulations containing a material amount of a non-aqueous ester solvent. The limitation distinguishes the claimed composition from formulations using ester solvents such as benzyl benzoate.

The phrase "substantially free" is inherently more flexible than "completely free." Claim 2 separately requires the composition to be completely free of a non-aqueous ester solvent. The distinction creates two infringement positions:

A composition with no detectable or intentionally added ester solvent may implicate claim 2.
A composition with trace residual ester solvent may still implicate claim 1, depending on the construction of "substantially free."
A composition containing a functional amount of benzyl benzoate would face a stronger non-infringement position, although the result would depend on the amount, role, and claim construction.

The patent does not necessarily exclude every ester compound. The relevant question is whether the accused ingredient is a non-aqueous ester solvent and whether it is present at a level inconsistent with the claimed limitation.

What formulations are protected by claims 3 through 10?

Claims 3 through 10 progressively narrow the formulation.

Claim	Limitation
3	The nonionic surfactant is polysorbate 80
4	The ricinoleate vehicle is castor oil
5	The antioxidant is a vitamin E compound
6	The vitamin E compound is alpha-tocopherol
7	The alcohol contains ethanol and benzyl alcohol
8	Ethanol and benzyl alcohol are present in approximately equivalent weight/volume amounts
9	The formulation contains 10% w/v ethanol and 10% w/v benzyl alcohol
10	Castor oil satisfies specified carbonyl, peroxide, iodine, and/or Gardner color values

A formulation containing polysorbate 80, castor oil, alpha-tocopherol, 10% w/v ethanol, and 10% w/v benzyl alcohol would fall within the most commercially specific portion of the claim set if it also satisfies the ester-solvent exclusion.

Why does castor-oil quality matter?

Claim 10 turns the vehicle into a quality-controlled pharmaceutical raw material. The stated parameters are:

Carbonyl value: 0.5 micromole/gram or less.
Peroxide value: 5.0 meq O2/kg or less.
Iodine value: 85 g iodine/100 g castor oil or less.
Gardner 1933 value: 1.5 or less.

These limitations target oxidation, color, unsaturation, and degradation characteristics of castor oil. They may create a significant manufacturing barrier because infringement analysis would require raw-material testing, supplier records, batch specifications, and analytical methods.

The use of "and/or" in claim 10 is important. Depending on the final construction, the claim may cover castor oil satisfying one or more of the listed parameters rather than requiring every parameter simultaneously. A competitor should not assume that avoiding a single specification avoids the claim.

What stability limitations are claimed?

Claims 11 and 12 add post-manufacture performance requirements:

Claim 11 requires total impurities of no more than 1% after storage at 25°C for three months.
Claim 12 requires fulvestrant sulfone of no more than 0.5% after the same storage period.

These claims are narrower than claim 1 because they depend on the composition of claim 1 and impose measurable stability outcomes. They may be relevant in litigation because an accused product can be tested under the specified storage conditions.

The claims raise several analytical issues:

The patent must define how "total impurities" are measured.
The analytical method must distinguish fulvestrant sulfone from other degradation products.
The storage container, humidity, light exposure, sampling, and assay conditions may affect the result.
A batch-specific result may not establish that every commercial batch satisfies the limitation.
A stability claim may be difficult to prove before sufficient product aging has occurred.

Claims 11 and 12 can strengthen the patent against products using the same excipient architecture but producing higher degradation levels. They also create potential validity and enablement questions if the disclosure does not support the full breadth of the claimed formulation combinations.

Does the patent cover syringes and vials?

Yes. Claims 13 and 14 cover:

A syringe containing 2.5 mL to 5 mL of the composition.
A vial containing 2.5 mL to 5 mL of the composition.

These claims are directed to product-by-container configurations rather than the formulation alone. A prefilled syringe containing the claimed composition presents a separate infringement theory from bulk formulation manufacture.

The volume range is commercially relevant because fulvestrant injections are commonly supplied in prefilled syringe presentations. A product outside the 2.5 mL to 5 mL range may avoid claims 13 and 14 while remaining exposed under claim 1 or claim 15.

What does claim 15 protect?

Claim 15 covers a method of treating hormone receptor-positive metastatic breast cancer by administering a therapeutically effective amount of the composition of claim 1.

The method claim requires:

A subject in need of treatment.
Hormone receptor-positive metastatic breast cancer.
Administration of the claimed fulvestrant composition.
A therapeutically effective amount.
Treatment of the disease.

Claim 15 does not cover treatment using every fulvestrant formulation. The administered product must satisfy claim 1. It also does not expressly require a particular dosing schedule, although the approved fulvestrant regimen may be relevant to induced-infringement and labeling analysis.

When does US Patent 9,833,459 lose exclusivity?

US Patent No. 9,833,459 issued on December 5, 2017. Its enforceable term is generally calculated from the earliest effective nonprovisional or international filing date, not from the issue date, under the 20-year patent term rule. Any terminal disclaimer, patent-term adjustment, or patent-term extension could alter the expiration date. (35 U.S.C. § 154.)

Based on the patent's 2010s filing history, the ordinary term would fall in the early-to-mid 2030s. The issue date alone does not establish the expiration date. Patent-term adjustment must be reviewed in the USPTO Patent Center record before using a specific expiration date in a launch or licensing decision.

The patent term is separate from FDA regulatory exclusivity. FDA exclusivity can expire before the patent, and an ANDA applicant may challenge the patent before its expiration through a Paragraph IV certification.

What is the Orange Book status of US 9,833,459?

A patent is not automatically Orange Book-listed merely because it covers a drug formulation. For listing, the patent must claim the approved drug, a formulation or composition of the approved drug, or an approved method of use under the FDA Orange Book framework. (FDA, 2024a.)

For fulvestrant, the commercial reference product is Faslodex, marketed by AstraZeneca. The original marketed formulation has historically included fulvestrant, castor oil, alcohol components, and benzyl benzoate. A formulation claim requiring the product to be substantially free of a non-aqueous ester solvent may not read on a reference formulation that contains benzyl benzoate.

That distinction creates three possible regulatory positions:

Issue	Consequence
Patent listed for the reference product	An ANDA applicant may need a Paragraph IV certification or a statement that approval is sought after patent expiry
Patent not listed	The patent may still support infringement litigation, but it would not create an Orange Book certification obligation
Patent listed only for a method of use	A section viii carve-out may be available if the applicant omits the patented indication from labeling

The Orange Book entry, if any, must be checked against the current FDA patent listing for the relevant fulvestrant NDA. The patent claims alone do not establish an Orange Book listing.

What Paragraph IV risks exist for fulvestrant generics?

A generic applicant seeking approval before expiration could challenge the patent through:

Paragraph IV certification that the patent is invalid, unenforceable, or not infringed.
A non-infringement position based on the presence of an ester solvent.
A formulation design-around using a different vehicle, surfactant, antioxidant, alcohol, or container volume.
A challenge to the stability limitations in claims 11 and 12.
A challenge to the written description or enablement of the broad excipient combinations.

The strongest Paragraph IV defense would usually be a formulation that does not contain all claim 1 elements. For example, a product may reduce risk by:

Using an aqueous vehicle rather than a ricinoleate vehicle.
Using a non-ricinoleate oil.
Omitting the claimed antioxidant.
Using an ionic surfactant rather than a nonionic surfactant.
Retaining a non-aqueous ester solvent, if commercially and regulatorily acceptable.
Using a different alcohol system.
Providing a volume outside the syringe or vial ranges.

A design-around must be evaluated under both literal infringement and the doctrine of equivalents. Changing an excipient may also create pharmaceutical development, stability, and FDA comparability issues.

Which companies face competitive exposure?

The principal commercial exposure is for companies developing or marketing injectable fulvestrant products, including:

AstraZeneca, as the Faslodex reference-product sponsor.
Generic injectable manufacturers filing ANDAs for fulvestrant.
Contract manufacturers producing castor-oil-based fulvestrant injections.
Developers pursuing prefilled syringe presentations.
Suppliers of pharmaceutical-grade castor oil and antioxidant systems.

A biosimilar pathway is not the primary competitive route. Fulvestrant is a chemically synthesized small molecule, not a biologic. FDA approval is generally pursued through an ANDA under section 505(j), not through the biosimilar pathway under section 351(k). The Purple Book is therefore not the relevant exclusivity database for fulvestrant. (FDA, 2024b.)

How does this patent compare with the original Faslodex patent estate?

The patent estate can be divided into four layers:

Layer	Typical protection	Relevance to US 9,833,459
Active ingredient	Fulvestrant molecule and steroidal antiestrogen activity	Largely historical for early patents; does not define this patent
Original formulation	Injectable fulvestrant with oil, alcohol, surfactant, and ester solvent components	Potential prior-art and claim-overlap issue
Improved formulation	Reduced ester solvent, improved stability, controlled castor oil, impurity limits	Core subject of US 9,833,459
Product and use	Syringe, vial, indication, dosing, treatment	Claims 13-15

The commercial significance of US 9,833,459 depends on whether generic developers use the patented formulation architecture. A generic product with benzyl benzoate may avoid the central ester-free limitation, while a product designed to improve tolerability, stability, or regulatory acceptability by removing benzyl benzoate could move closer to the patent claims.

How strong is the patent estate?

The patent has meaningful commercial value but a narrower infringement perimeter than a basic compound patent.

Strengths

Claim 1 captures a complete excipient architecture rather than a single ingredient.
The ester-solvent exclusion distinguishes the formulation from conventional products.
Dependent claims identify commercially plausible embodiments.
Claims 11 and 12 add objective stability benchmarks.
Claims 13 and 14 cover common injectable container presentations.
Claim 15 links the composition to the principal fulvestrant treatment indication.

Weaknesses

The broad composition claim requires multiple formulation elements.
The ester-solvent language may create claim-construction disputes.
Prior art on fulvestrant injection formulations may be relevant to anticipation or obviousness.
Excipient substitutions may provide practical design-around routes.
Stability claims may require extended testing and may be vulnerable to variability in analytical methods.
The method claim depends on infringement of the composition limitation.

The strongest claims for enforcement are likely claims 1, 3, 4, 7, and 9 when an accused product uses the same recognizable excipient system. Claims 11 and 12 may provide additional leverage where the formulation is chemically similar but stability results differ.

What manufacturing and geographic barriers apply?

The patent is territorial. US 9,833,459 affects manufacture, importation, offer for sale, sale, and use in the United States under US patent law. It does not by itself block products in Europe, Canada, Japan, or other jurisdictions.

International risk depends on corresponding national patents in the family. A global freedom-to-operate review should separate:

US composition claims.
European formulation claims.
Canadian and Asian counterparts.
Manufacturing-site activities.
Importation of finished syringes or vials.
Supply of castor oil and other excipients.
Local regulatory patent-linkage rules.

The manufacturing barrier is strongest where the process uses a fixed supplier specification for low-peroxide, low-carbonyl castor oil and a controlled antioxidant system. A supplier certificate alone may not resolve infringement risk if the finished composition satisfies the claim. Batch testing, raw-material qualification, and retained samples can become central evidence in litigation.

What litigation and settlement issues should be monitored?

The key litigation trigger is an ANDA Paragraph IV notice identifying US 9,833,459. The statutory 45-day period for filing an infringement action under the Hatch-Waxman framework can trigger a 30-month stay of FDA approval, subject to statutory exceptions and court rulings. (21 U.S.C. § 355(j)(5)(B)(iii).)

Relevant disputes would likely concern:

Whether the generic formulation contains a ricinoleate vehicle.
Whether the product uses a nonionic surfactant.
Whether its antioxidant is within the claimed vitamin E category.
Whether benzyl alcohol and ethanol are present at approximately equivalent amounts.
Whether any benzyl benzoate or other ester solvent defeats the claim.
Whether the composition meets the impurity thresholds.
Whether a prefilled syringe or vial falls within the volume range.
Whether the patent is invalid over earlier fulvestrant formulations.

A settlement could include a licensed entry date, a formulation restriction, a no-challenge clause, or a supply agreement. No settlement terms should be inferred from the patent claims or FDA approval record alone.

Key Takeaways

US 9,833,459 is a fulvestrant formulation patent, not a basic molecule patent.
Claim 1 requires fulvestrant, an alcohol, a nonionic surfactant, an antioxidant, a ricinoleate vehicle, and substantial absence of a non-aqueous ester solvent.
The most commercially specific embodiment uses castor oil, polysorbate 80, alpha-tocopherol, 10% w/v ethanol, and 10% w/v benzyl alcohol.
Claims 11 and 12 protect impurity-performance results after three months at 25°C.
Claims 13 and 14 cover 2.5 mL to 5 mL syringes and vials.
Claim 15 covers treatment of hormone receptor-positive metastatic breast cancer with the claimed composition.
The patent's term is expected to extend into the 2030s, subject to the official patent-term calculation.
Generic risk turns primarily on formulation composition, not on fulvestrant itself.
A formulation containing a functional amount of benzyl benzoate may have a stronger non-infringement position against the ester-free limitation.
Fulvestrant is a small molecule, so ANDA litigation, not biosimilar litigation, is the relevant competitive framework.
Orange Book listing must be confirmed from the FDA record and cannot be established from the patent claims alone.

FAQs About US Patent 9,833,459

Does US 9,833,459 cover Faslodex itself?

It does not cover fulvestrant as a molecule. It covers a defined fulvestrant formulation and related syringes, vials, and treatment methods. Whether a particular Faslodex presentation falls within the claims depends on its complete excipient composition.

Can a fulvestrant generic avoid this patent by using benzyl benzoate?

Possibly. A product containing benzyl benzoate or another non-aqueous ester solvent may have a non-infringement position against the ester-free limitation, but the result depends on the amount, function, and construction of the claim language.

Are claims 11 and 12 composition claims or performance claims?

They are dependent composition claims with post-storage performance limitations. The accused product must satisfy the underlying composition requirements and the specified impurity result under the claimed storage condition.

Does a 5 mL fulvestrant vial fall within claim 14?

Yes, if it contains the composition of claim 1 and the vial contains 2.5 mL to 5 mL. The container volume alone is insufficient because the formulation must also meet claim 1.

Is a biosimilar filing required for fulvestrant?

No. Fulvestrant is a chemically synthesized small molecule. A generic applicant would ordinarily use the ANDA pathway rather than the biosimilar pathway.

References

U.S. Patent No. 9,833,459. (2017). Fulvestrant formulation. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024b). Purple Book: Database of licensed biological products. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024c). Faslodex (fulvestrant) prescribing information. AstraZeneca Pharmaceuticals LP.
21 U.S.C. § 355. (2024). New drugs.
35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Fresenius Kabi Usa	FULVESTRANT	fulvestrant	SOLUTION;INTRAMUSCULAR	210326-001	May 20, 2019	AO	RX	No	No	9,833,459	⤷ Start Trial	Y			TREATMENT OF HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN	⤷ 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

Details for Patent: 9,833,459

Which drugs does patent 9,833,459 protect, and when does it expire?

Summary for Patent: 9,833,459