Details for Patent: 4,038,389

Summary for Patent: 4,038,389

Title:	Medroxyprogesterone acetate compositions
Abstract:	A pharmaceutical vehicle for parenteral administration of medroxyprogesterone acetate is disclosed comprising an aqueous solution of sodium sulfate, quaternary ammonium wetting agent, and a member selected from glycerin, propylene glycol, polyethylene glycol, and polypropylene glycol. The compositions may contain a non-ionic hydrophilic colloid as a preferred adjuvant. Compositions are useful for suspending large amounts, e.g., from 200 to 600 mg./ml. of medroxyprogesterone acetate and maintaining suitable suspendability and syringeability characteristics and are used for the known therapeutic indications for medroxyprogesterone acetate.
Inventor(s):	Donald J. Lamb
Assignee:	Pharmacia and Upjohn Co
Application Number:	US05/671,918
Patent Claim Types: see list of patent claims	Composition; Dosage form;

United States Patent 4,038,389 Scope and Claims Analysis: Medroxyprogesterone Acetate Aqueous Parenteral Suspension Formulation Patent Landscape

United States Patent 4,038,389 claims a specific aqueous suspension formulation for parenteral administration of medroxyprogesterone acetate (MPA) defined by narrow concentration windows and functional ingredient classes, with added limitations around particle size and an optional non-ionic hydrophilic colloid.

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What is US Patent 4,038,389 and what formulation does it cover?

Answer: US 4,038,389 claims an aqueous parenteral suspension of medroxyprogesterone acetate with:

• MPA: about 200 to 600 mg/mL suspended
• Water as the continuous phase
• Sodium sulfate: about 0.8% to 1.5% w/v
• Quaternary ammonium wetting agent: about 0.1% to 1.4% w/v (parenterally acceptable)
• Glycol/polyol cosolvent member: about 2% to 5% w/v selected from glycerin, propylene glycol, polyethylene glycol, polypropylene glycol
• Optional: non-ionic hydrophilic colloid not exceeding 1.5% w/v
• Optional/dependent: particle fineness where 99% less than 10 microns and 75% less than 5 microns

Claimed formulation is defined by ingredient class + tight quantitative ranges

The claims are not “functional” at a high level; they are range-locked and class-locked, which narrows literal scope to compositions meeting all stated ranges and selections.

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What are the independent claim limitations in plain terms (Claim 1)?

Claim 1 is the core composition claim. It requires all elements:

1. Drug substance: suspended medroxyprogesterone acetate
2. Concentration of suspended MPA: 200 to 600 mg/mL
3. Vehicle: water
4. Salt component: sodium sulfate at 0.8% to 1.5% w/v
5. Wetting agent component: parenterally acceptable quaternary ammonium wetting agent at 0.1% to 1.4% w/v
6. Polyol/cosolvent/glycol component: 2% to 5% w/v of one member selected from:
   • glycerin
   • propylene glycol
   • polyethylene glycol
   • polypropylene glycol

Why Claim 1 is narrow in practice

To fall within Claim 1 literally, a product must satisfy every numeric window and include the specified ingredient classes, including:

• quaternary ammonium wetting agent (not surfactant broadly, but a defined class)
• sodium sulfate at the specified % range
• one selected polyol/glycol member at 2–5% w/v

This makes routine formulation latitude risky. Small deviations (for example sodium sulfate at 0.75% or at 1.6% w/v) can move a product outside literal coverage.

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How do Claims 2–4 expand or restrict scope (optional colloid and particle size)?

Claim 2: Does adding a non-ionic hydrophilic colloid change protection?

Claim 2 adds a limitation to Claim 1:

• includes a parenterally acceptable non-ionic hydrophilic colloid
• at ≤ 1.5% w/v

Effect on scope: Claim 2 captures formulations that include the colloid at up to the cap. It does not require it to be present in Claim 1, so Claim 2 is a subset of Claim 1.

Claim 3: How much does particle fineness narrow the claim (99% <10 µm; 75% <5 µm)?

Claim 3 adds to Claim 1:

• MPA suspended particle fineness:
  • 99% less than 10 microns
  • 75% less than 5 microns

Effect on scope: Claim 3 is narrower than Claim 1 because it adds a measurable particle size distribution. If a product’s particle distribution does not meet these thresholds, it avoids Claim 3 (but may still fall under Claim 1 if composition ranges match).

Claim 4: Does combining particle size + non-ionic hydrophilic colloid create a tighter pocket?

Claim 4 adds both:

• the particle fineness limitations of Claim 3
• plus the non-ionic hydrophilic colloid ≤ 1.5% w/v (as in Claim 2)

Effect on scope: Narrowest claim in the set, but it provides an additional literal hook for products that meet both particle size and colloid criteria.

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What patents or claim elements are most likely to be the “real” drivers of scope?

The strongest scope-defining features (highest leverage in claim interpretation and infringement analysis) are:

1. MPA suspension concentration (200–600 mg/mL)
   • High mg/mL range suggests a ready-to-inject high-concentration depot-style suspension.
2. Sodium sulfate 0.8–1.5% w/v
   • Salt identity and range are specific.
3. Quaternary ammonium wetting agent 0.1–1.4% w/v
   • This is class-locked and range-locked.
4. Polyol/glycol selection at 2–5% w/v
   • One of specified members is required; changing to a different excipient not in the group breaks literal coverage.
5. Particle fineness distribution (Claims 3 and 4)
   • A distribution metric is often product-specific and can be used as a design-around point.

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How would a generic or competitor avoid literal infringement of US 4,038,389?

Avoid by moving outside a numeric window

Literal avoidance is most straightforward by changing at least one required concentration outside the claimed range:

• sodium sulfate below 0.8% or above 1.5% w/v
• quaternary ammonium wetting agent below 0.1% or above 1.4% w/v
• polyol/glycol outside 2–5% w/v
• MPA outside 200–600 mg/mL

Avoid by changing the ingredient classes

Substitution risks:

• Replace quaternary ammonium wetting agent with a non-quaternary surfactant class.
• Replace sodium sulfate with a different salt (chloride, citrate, phosphate).
• Use a polyol/cosolvent not in the claimed set.

Avoid by changing particle fineness

For products likely to need to be close to the Claim 1 composition, Claims 3–4 can be avoided by producing particle distributions outside:

• 99% < 10 µm or 75% < 5 µm

A product may still be within Claim 1 if it meets all Claim 1 composition ranges, but it can defeat Claims 3 and 4.

Exploit optional vs required elements

• Claim 2 and Claim 4 require a non-ionic hydrophilic colloid ≤ 1.5% w/v.
• Claim 1 does not require this colloid. So a design-around that omits the colloid would avoid Claims 2 and 4 but would not necessarily avoid Claim 1.

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What does this imply about the patent landscape for MPA injectable suspensions in the US?

US 4,038,389’s claims are formulation-centric (composition elements plus optional particle size). In this space, patent estates for MPA injectable products typically cluster into:

• formulation composition patents (ranges, surfactants/wetting agents, salts, viscosity modifiers)
• particle size or milling/process patents
• manufacturing and redispersion stability patents
• packaging and container-closure system patents (less likely to be captured by these composition claims)
• method-of-use patents (less likely here because the claims are not use-driven)

Where this patent sits: It protects a specific “recipe” framework for a depot-style aqueous MPA suspension.

Practical competitive mapping: what other patents are likely to overlap

Even without listing specific other patent numbers here, the claim architecture points to typical overlap zones:

• other patents that claim depot MPA suspensions with different surfactant systems (non-quaternary, different wetting agents)
• patents that claim sodium-free or different-salt systems
• patents that claim different co-solvents or different polyol selection
• patents that claim particle size targets or dispersibility thresholds

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How strong is the patent estate based on claim structure (scope strength and enforceability)?

Strength indicators from the claim text

• The claims are composition-specific and include:
  • defined ranges for multiple excipients
  • defined classes for the wetting agent and polyol member
• This creates clear infringement benchmarks for a lab/CMC dossier comparison.
• The presence of a particle size distribution in dependent claims increases the chance of a factual test for infringement.

Strength limitations

• Because the claims require meeting all windows simultaneously, design-around via modest formulation changes is possible.
• If a competitor’s formulation uses different excipient classes or different salts or different quaternary chemistry, literal risk drops.

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What Orange Book status and FDA regulatory linkage should be expected for this patent?

US patents like 4,038,389, when tied to an approved injectable product, are commonly listed in the FDA Orange Book for:

• the approved drug product(s) containing the same active ingredient (medroxyprogesterone acetate)
• specific dosage forms and strengths

However, this analysis is limited to claim scope. Orange Book listing does not follow automatically from claim text. The only reliable linkage would come from the Orange Book record for the specific NDA/ANDA/BLA product and its listed patents.

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How does this affect generic entry risk for parenteral MPA suspensions?

The claim set suggests two infringement-analysis tracks:

1. Composition match risk (Claim 1)
   • If a generic’s aqueous suspension meets all ingredient classes and ranges, Claim 1 risk rises.
2. Particle size and colloid match risk (Claims 3–4)
   • Even if composition is close, failure to hit the defined particle distribution reduces risk for Claims 3 and 4.

Likely litigation posture for this type of patent

A typical enforcement focus would compare:

• formulation lab results (HPLC for MPA, excipient assays, salt analysis)
• particle sizing (laser diffraction or microscopy method used consistently)
• wetting agent identity and concentration

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Timeline and exclusivity: when would the patent stop excluding generics?

The claims supplied do not include:

• grant year confirmation
• specific expiration date
• maintenance fee status
• any terminal disclaimer
• PTA/adjustments

So the only actionable statement from the provided text is that the patent is US 4,038,389 and the claims define formulation scope. A definitive exclusivity timeline cannot be computed from the claim text alone.

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Key Takeaways

• US 4,038,389 claims a specific aqueous parenteral suspension recipe for medroxyprogesterone acetate with tight ranges for sodium sulfate (0.8–1.5% w/v), a quaternary ammonium wetting agent (0.1–1.4% w/v), and a 2–5% w/v polyol/glycol selected from glycerin/propylene glycol/PEG/PPG.
• Dependent claims add optional non-ionic hydrophilic colloid (≤1.5% w/v) and optional particle fineness thresholds (99% <10 µm; 75% <5 µm).
• Literal infringement risk is driven by meeting all required concentration windows and ingredient classes simultaneously; design-arounds are feasible by shifting at least one required range or substituting outside the specified ingredient classes.

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FAQs

1. What excipients are explicitly required in US 4,038,389 medroxyprogesterone acetate suspension claims?
Sodium sulfate, a quaternary ammonium wetting agent, and one selected polyol/glycol from glycerin, propylene glycol, polyethylene glycol, or polypropylene glycol; water is required as the vehicle.

2. Does US 4,038,389 require a non-ionic hydrophilic colloid?
No. It is required only in Claims 2 and 4, and only up to 1.5% w/v.

3. What particle size targets are used to narrow Claims 3 and 4?
99% of particles must be less than 10 microns and 75% less than 5 microns.

4. If a competitor changes only the particle size but keeps the excipient ranges identical, which claims are at risk?
Claims 1 may still be at risk if composition ranges match; Claims 3 and 4 would be avoided if the particle distribution fails the specified thresholds.

5. Which is a more effective design-around lever: changing the wetting agent or changing sodium sulfate concentration?
Either can work, but changing sodium sulfate concentration or quaternary wetting agent concentration outside the claimed ranges is directly aligned to the claim’s range-locking structure.

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References

1. US Patent 4,038,389 (claims provided in prompt).

Drugs Protected by US Patent 4,038,389

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate