Details for Patent: 9,271,990

« Back to Dashboard

Which drugs does patent 9,271,990 protect, and when does it expire?

Patent 9,271,990 protects FULVESTRANT and is included in one NDA.

Summary for Patent: 9,271,990

Title:	Fulvestrant formulations
Abstract:	The invention provides a fulvestrant composition comprising a pharmaceutically acceptable alcohol, polysorbate 80, an antioxidant, and castor oil, which is substantially or completely free of a non-aqueous ester solvent and which demonstrates excellent storage stability. The composition may be used to treat hormone receptor positive metastatic breast cancer in a subject.
Inventor(s):	Jabar A. FARAJ
Assignee:	Fresenius Kabi USA LLC
Application Number:	US14/181,244
Patent Claim Types: see list of patent claims	Use; Composition;

Scope and claims of US Patent 9,271,990: fulvestrant stabilization in ethanol/benzyl alcohol with polysorbate 80 and antioxidant plus defined castor oil

US 9,271,990 is a formulation and use patent built around stabilizing fulvestrant (a non-aqueous injectable SERD) using a specific excipient stack: fulvestrant + polysorbate 80 + antioxidant (vitamin E species) + castor oil with specified quality metrics, in an alcoholic system that is “substantially free” or “completely free” of a non-aqueous ester solvent. The independent claim is a composition claim; dependent claims add tighter solubility, antioxidant identity, alcohol ratio, excipient specifications, and stability-imposed impurity limits. Final claim coverage extends to device packaging (prefilled syringe/vial size ranges) and a method-of-treatment claim for hormone receptor positive metastatic breast cancer.

---

What does US 9,271,990 claim, and what is the core invention?

Featured snippet answer: US 9,271,990 claims fulvestrant injectable compositions stabilized with polysorbate 80, an antioxidant (vitamin E including α-tocopherol), and a castor oil grade defined by quality indices, using an ethanol/benzyl alcohol solvent system that is substantially free or completely free of a non-aqueous ester solvent, with enforced storage impurity and fulvestrant sulfone limits.

Claim architecture at a glance

• Independent composition claim (Claim 1): composition comprising
  • fulvestrant
  • pharmaceutically acceptable alcohol (later narrowed to ethanol + benzyl alcohol)
  • polysorbate 80
  • antioxidant
  • castor oil
  • substantially free of a non-aqueous ester solvent
• Binary solvent restriction (Claim 2): “completely free” of a non-aqueous ester solvent.
• Antioxidant narrowing (Claims 3-4): antioxidant is a vitamin E compound; specifically α-tocopherol.
• Alcohol composition narrowing (Claims 5-7): alcohol comprises ethanol + benzyl alcohol; ratio requirement (approx. equivalent w/v); example embodiment at 10% w/v ethanol + 10% w/v benzyl alcohol.
• Castor oil quality specification (Claim 8): castor oil characterized by limits on carbonyl value, peroxide value, iodine value, and/or Gardner value.
• Stability/impurity performance limits (Claims 9-10):
  • after 25°C for 3 months, total impurities ≤ 1%
  • after 25°C for 3 months, fulvestrant sulfone ≤ 0.5%
• Quantitative formulation window (Claim 11):
  • fulvestrant 5–10% w/v
  • alcohol 10–30% w/v
  • polysorbate 80 0.05–0.2% w/v
• Container-closure form factors (Claims 12-13):
  • syringe 2.5–5 mL
  • vial 2.5–5 mL
• Specific exemplar composition (Claim 14):
  • 5% w/v fulvestrant, 10% ethanol, 10% benzyl alcohol
  • 0.12% w/v polysorbate 80
  • 0.06% w/v α-tocopherol
  • castor oil
  • substantially free of a non-aqueous ester solvent
• Method-of-stabilizing formulation (Claim 15): making the mixture with the same excipient and solvent restriction; storage-imposed impurity limits in dependent Claim 16.
• Method-of-use (Claim 17): treating hormone receptor positive metastatic breast cancer with the composition of Claim 1.

---

How broad is “substantially free” of a non-aqueous ester solvent in Claim 1?

Featured snippet answer: Claim 1’s solvent restriction is the key breadth lever. It captures formulations that avoid non-aqueous ester solvents to a degree that qualifies as “substantially free,” while Claim 2 further captures those that are “completely free.”

Scope implications

• The independent claim does not specify a numeric threshold for “substantially free.” That phrase typically creates an evidentiary and claim-construction fight: whether trace amounts of an ester excipient are permitted, and what qualifies as a “non-aqueous ester solvent.”
• Dependent Claim 2 narrows further. A competitor that uses any non-aqueous ester solvent at all may be outside Claim 2 but still potentially inside Claim 1 if the ester content is argued to be “substantially free.”

Practical design-around pressure points

• Any reformulation that introduces a non-aqueous ester solvent (as a carrier phase or co-solvent) is a direct threat to both Claims 1 and 2.
• A competitor using alternative alcohol systems must preserve the core excipient stack (polysorbate 80 + antioxidant + castor oil) and still meet the solvent restriction.

---

Which fulvestrant excipients are required, and what does that mean for product design?

Featured snippet answer: The claims require a fulvestrant injectable composition with polysorbate 80 and a castor oil phase, plus an antioxidant that is specifically a vitamin E compound in narrower claims.

Required components and how they constrain formulation space

1. Fulvestrant
   • Present in a claimed window in Claim 11 (5–10% w/v) and exemplified in Claim 14 (5% w/v).
2. Polysorbate 80
   • Required in all claims depending on Claim 1 base; quantitatively constrained in Claim 11 (0.05–0.2% w/v) and exemplified in Claim 14 (0.12% w/v).
3. Antioxidant
   • Required in Claim 1, narrowed to vitamin E species in Claim 3, and to α-tocopherol in Claim 4.
4. Castor oil
   • Required in Claim 1; narrowed by quality specs in Claim 8.
   • This is a high-value constraint because quality indices are harder to “equivalently” satisfy without matching the source/material specs and manufacturing controls.
5. Alcohol system
   • Claimed as “pharmaceutically acceptable alcohol” in Claim 1.
   • Narrowed in Claims 5–7 to ethanol + benzyl alcohol with an “approx. equivalent” w/v amounts constraint and exemplified at 10% w/v each in Claim 7.
   • Quantified in Claim 11 (10–30% w/v total alcohol range).

What is the “composition of Claim 1” coverage boundary?

To practice Claim 1, a product must include:

• fulvestrant
• polysorbate 80
• an antioxidant
• castor oil
• an alcohol system
• and avoid non-aqueous ester solvent to the degree set by “substantially free.”

Even if an accused product differs on castor oil quality or antioxidant identity, it may still fall within Claim 1 unless those features are required in the independent claim (they are). However, dependent claims create additional “validity and infringement” hurdles for narrower variants.

---

How do the castor oil quality limits in Claim 8 narrow infringement risk?

Featured snippet answer: Claim 8 requires castor oil meeting defined limits for carbonyl value, peroxide value, iodine value, and/or Gardner 1933 value, creating a material-spec barrier that can be used for both design-around and infringement defense.

Quantitative thresholds (Claim 8)

Castor oil characterized by one or more of:

• carbonyl value ≤ 0.5 micromole/gram
• peroxide value ≤ 5.0 meq O2/kg
• iodine value ≤ 85 g iodine/100 g castor oil
• Gardner 1933 value ≤ 1.5

Litigation significance (scope and evidence)

• These tests are lab-based and material-source-specific. A manufacturer switching to a different castor oil grade or supply may reduce the likelihood of meeting the exact indices.
• In infringement litigation, the presence of quality specs allows targeted discovery: COAs, raw material lot records, stability studies, and test method validation.

---

What do the storage-based impurity and sulfone limits require?

Featured snippet answer: Claims 9 and 10 impose performance gates: after storage at 25°C for 3 months, total impurities must be ≤ 1%, and fulvestrant sulfone must be ≤ 0.5%.

Claim 9: total impurities limit

• Storage condition: 25°C for 3 months
• Spec: total impurities ≤ 1%

Claim 10: fulvestrant sulfone limit

• Same storage condition
• Spec: fulvestrant sulfone ≤ 0.5%

Claim construction leverage

• These are not just compositional limits; they are outcome limits. That can shift disputes toward:
  • accelerated vs real-time stability testing approaches
  • comparability of analytical methods and reporting thresholds
  • whether sulfone is measured as a specific named impurity and how “not more than” is handled statistically

---

What dose and concentration windows are explicitly covered?

Featured snippet answer: Claim 11 locks in a quantitative composition window for fulvestrant (5–10% w/v), total alcohol (10–30% w/v), and polysorbate 80 (0.05–0.2% w/v).

Windows (Claim 11)

• fulvestrant: 5–10% w/v
• pharmaceutically acceptable alcohol: 10–30% w/v
• polysorbate 80: 0.05–0.2% w/v

Exemplar (Claim 14)

• fulvestrant: 5% w/v
• ethanol: 10%
• benzyl alcohol: 10%
• polysorbate 80: 0.12%
• α-tocopherol: 0.06%
• castor oil
• substantially free of a non-aqueous ester solvent

These windows align Claim 14 as an explicit member of the broader Claim 11 range, tightening infringement arguments around any product designed to match the exact example.

---

Do the claims cover syringes and vials, and how does that affect packaging liability?

Featured snippet answer: Yes. Claims 12 and 13 extend coverage to container volumes (2.5–5 mL) for syringes and vials containing the composition of Claim 1.

• Claim 12: syringe containing 2.5–5 mL of Claim 1 composition
• Claim 13: vial containing 2.5–5 mL of Claim 1 composition

Practical effect

• Packaging range claims can create multiple liability nodes:
  • bulk formulation supplier
  • final drug product manufacturer
  • fill-finish operator
• If a generic changes fill volume, it may escape Claims 12–13 but not necessarily Claim 1 or Claim 17.

---

What method claims exist besides formulation composition?

Featured snippet answer: Claim 15 claims a method of stabilizing fulvestrant by forming the specified mixture; Claim 16 adds the same 25°C/3-month impurity limit as Claim 9.

Claim 15: method-of-stabilizing

• form a mixture comprising:
  • 5–10% w/v fulvestrant
  • 10–30% w/v alcohol
  • 0.05–0.2% w/v polysorbate 80
  • antioxidant
  • castor oil
• mixture is substantially free of a non-aqueous ester solvent

Claim 16: method performance gate

• after 25°C for 3 months, total impurities ≤ 1%

Litigation posture

• Method claims can be used to pursue manufacturing conduct even where the end product composition is argued over. If the manufacturing step is performed with the claimed constraints, Claim 15 can anchor a different infringement narrative.

---

What is claimed for treatment of metastatic breast cancer?

Featured snippet answer: Claim 17 claims a treatment method for hormone receptor positive metastatic breast cancer using administration of a therapeutically effective amount of the Claim 1 composition.

• Claim 17: administering the composition of Claim 1 to treat hormone receptor positive metastatic breast cancer.

Practical effect

• Method-of-use coverage raises both:
  • physician administration and label alignment issues (if the generic’s proposed label targets the same indication)
  • “product-by-process” style arguments where composition overlap is established but clinical labeling differs

---

What could competitors do to avoid infringement, given these claim constraints?

Featured snippet answer: The most effective design-around targets are (i) the non-aqueous ester solvent avoidance requirement, (ii) substituting away from the vitamin E/α-tocopherol antioxidant family in narrower claims, and (iii) using castor oil grades that do not meet the quality indices, while also shifting concentration windows or alcohol ratios to reduce overlap with dependent claims.

High-impact design variables

• Ester solvent strategy
  • Introduce a non-aqueous ester solvent to fall outside “substantially free” and “completely free” claims.
• Antioxidant strategy
  • Replace vitamin E species with a different antioxidant system to reduce exposure to Claims 3-4 (but Claim 1 still requires an antioxidant generally).
• Castor oil material-spec strategy
  • Use castor oil with COA values exceeding one or more of the Claim 8 thresholds.
• Concentration and fill strategy
  • Move outside the 5–10% fulvestrant and/or 10–30% alcohol ranges in Claim 11.
  • Change fill volumes to avoid Claims 12–13.

Because Claim 1 is broad on antioxidant identity and alcohol identity (before dependent narrowing), the safest design-around typically needs to break Claim 1’s core constraints, not just dependent claims.

---

What is the patent landscape around US 9,271,990 (what patents typically sit around this claim theme)?

Featured snippet answer: US 9,271,990 belongs to a formulation-and-stabilization cluster for fulvestrant injectables, typically adjacent to patents covering (i) fulvestrant solvent systems, (ii) surfactant and antioxidant choices, (iii) impurity control including fulvestrant sulfone, and (iv) delivery form factors (syringe/vial).

However, without the full bibliographic and family data for US 9,271,990 (publication numbers, application filing date, priority chain, assignee, and related family members), a complete mapped landscape with exact neighboring patent numbers cannot be produced.

---

Key takeaways

• US 9,271,990 is a formulation stabilization patent centered on fulvestrant + polysorbate 80 + antioxidant + castor oil in an alcohol solvent system that is substantially free or completely free of non-aqueous ester solvent.
• Dependent claims tighten the field to vitamin E antioxidants (including α-tocopherol), ethanol/benzyl alcohol mixtures, defined castor oil quality indices, and strict 25°C/3-month impurity and sulfone limits.
• Claims extend beyond the composition into specific fill-volume syringe/vial formats and include a method-of-stabilizing manufacturing claim and a method-of-use treatment claim for HR+/metastatic breast cancer.
• The most litigation-relevant proof points are castor oil COA/test results, solvent/ester content documentation, analytical impurity profiles, and stability study data at the stated conditions.

---

FAQs

1) Does US 9,271,990 cover fulvestrant with any antioxidant, or only vitamin E?
Claim 1 requires an antioxidant generally; Claims 3-4 narrow that antioxidant to vitamin E compounds and specifically α-tocopherol.

2) What exact stability endpoints are claimed for impurity control?
After storage at 25°C for 3 months, total impurities must be ≤ 1% (Claim 9) and fulvestrant sulfone must be ≤ 0.5% (Claim 10).

3) Are syringes and vials part of the claimed invention or only the formulation?
Both. Claims 12-13 claim syringes and vials containing 2.5–5 mL of the Claim 1 composition.

4) Can a product outside the 5–10% fulvestrant range still infringe?
It may still infringe Claim 1 because Claim 1 does not set the 5–10% range. The 5–10% window is explicitly claimed in Claim 11 and tied to the method claim.

5) What is the strongest claim lever for an infringement dispute?
The “substantially free/completely free” requirement for a “non-aqueous ester solvent” plus the castor oil quality metrics and stability-based impurity/sulfone limits provide the highest evidentiary anchors.

---

References (APA)

1. United States Patent 9,271,990.

Drugs Protected by US Patent 9,271,990

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	9,271,990		Y			TREATMENT OF HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN