Details for Patent: 5,264,446

Summary for Patent: 5,264,446

Title:	Solid medicament formulations containing nifedipine, and processes for their preparation
Abstract:	The invention is directed to the provision of solid pharmaceutical compositions (and methods for their preparation) containing nifidipine crystals with a specific surface area of 1.0 to 4.0 m2/g., in admixture with a solid diluent. The said compositions overcome the deficiencies of prior art compositions containing nifidipine, which is known to have effect as a coronary vasodilator.
Inventor(s):	Ahmed Hegasy, Klaus-Dieter Ramsch
Assignee:	Bayer Pharma AG
Application Number:	US07/892,439
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Scope and Patent Landscape for US Patent 5,264,446 Covering Sustained-Release Nifedipine Using Specific Surface-Area Crystals (1.0–4 m²/g)

US Patent 5,264,446 is a focused crystalline-formulation and use patent for sustained-release (SR) nifedipine. The claims are built around a measurable material parameter: nifedipine crystal specific surface area (SSA) in defined ranges (1.0 to 4 m²/g; dependent narrower “about” and subranges), formulated as a solid composition with a solid diluent, and optionally administered via multiple dosage forms. The legal center of gravity is claim construction around (i) how SSA is defined/tested, (ii) whether “in admixture with a solid diluent” is satisfied by common excipient systems, and (iii) what evidentiary standard is required to prove “to result in a sustained release” when the claim is outcome-driven.

What is claimed in US Patent 5,264,446 (nifedipine SSA crystals for sustained-release)?

Core inventive concept: SR nifedipine delivered by using nifedipine crystals having a specific surface area within defined numeric bands, combined with a solid diluent in solid pharmaceutical compositions and in patient treatment methods for hypertension.

How broad are the claim elements? (element-by-element claim scope)

1) Active ingredient limitation: nifedipine crystals with defined specific surface area

• Claim 1 (base): SSA 1.0 to 4 m²/g.
• Claims 5–6–9–10 (dependent variants): SSA narrowed by “about” to 1.2 to 3.6 m²/g.
• Claims 9–10–11 (further variant): SSA narrowed to 1.3 to 3.1 m²/g.
• Claims are not limited by polymorph name in the provided text, but they are tightly constrained by a physical property (SSA) that can function like a surrogate for certain processing states.

Practical implication: In infringement analysis, the dispositive question becomes whether the accused nifedipine SR product uses crystals whose SSA falls within the claimed ranges, and whether the accused SSA corresponds to the claim’s definition and test method.

2) Composition limitation: solid pharmaceutical composition with solid diluent

• Claims 1, 5, 9: “solid pharmaceutical composition… in admixture with a solid diluent”
• Claims 2, 6, 10: “solid medicament in dosage unit form… in admixture with a solid diluent”
• Claims 3, 7, 11: same concept but expressly lists dosage forms

Scope drivers:

• The claims require “solid diluent” but do not, in the claim text you provided, specify which excipients qualify (e.g., lactose, mannitol, microcrystalline cellulose, starch, etc.).
• That excipient flexibility often expands coverage, unless the patent specification limits “solid diluent” to specific excipient types or functional roles.

3) Functional-outcome limitation: “to result in sustained release of nifedipine”

• Present in each composition and medicament claim via “to result in a sustained release of nifedipine.”
• Present in method claims via the improvement in treating hypertension by administering the specified crystals “to result in sustained release.”

Legal consequence: Outcome language can be litigated as:

• a required property of the claimed product (product-by-structure framed as a process effect), or
• a statement of intended use that may be read as limiting depending on claim construction.

In many SR formulation cases, courts often treat sustained-release as requiring evidence that the formulation actually behaves as SR under relevant test conditions, but the precise standard depends on claim language and specification anchoring.

4) Dosage form flexibility

Claim 3/7/11 cover:

• tablets, pills, dragees, capsules, suppositories, sachets, and two-layer tablets

Scope consequence: A wide set of oral and even rectal presentations are potentially within scope if the SSA and diluent limitations are satisfied.

5) Method-of-use claim scope

Claims 4, 8, 12:

• Treating hypertension by administering nifedipine crystals with the SSA range + solid diluent, where the improvement is employing crystals with the SSA range “to result in sustained release.”

Scope consequence: Even if formulation composition claims are avoided by excipient selection or dosage form design, a product using the claimed SSA crystals could still present risk under method claims if the medical use is for hypertension with SR effect.

What do the dependent claims materially change?

• Dependent claims narrow the SSA bands, creating a graded claim ladder:
  • Broadest: 1.0–4 m²/g
  • Mid: about 1.2–3.6 m²/g
  • Narrowest: about 1.3–3.1 m²/g (and the non-“about” 1.3–3.1 appearing in claim 11 text)

In practice: If an accused product uses SSA near the edges, the broad claim may be enough even if a narrower dependent range is missed. If SSA is clearly outside 1.0–4 m²/g, all claims based on SSA are structurally avoided.

How does specific surface area function as the infringement trigger (testing, equivalence, and design-around)?

Featured issue: SSA is a measurable parameter; it is also a litigation flashpoint because measurement methods can vary (BET gas adsorption vs other approaches; sample drying; milling state; wet vs dry; particle size distributions; moisture effects).

What SSA ranges imply for design-around

Because the claim tracks SSA numerically, common design-around strategies include:

• Adjusting crystallization conditions or milling to move SSA below 1.0 or above 4.0 m²/g.
• Using different processing routes that produce crystals with substantially different SSA.
• Blending grades of nifedipine crystals to shift the effective SSA distribution outside the claim.

However, without the patent’s specification and any prosecution history, the scope remains anchored to the numeric SSA bounds. A design-around must therefore address:

• the SSA of the crystals actually used in the finished product, and
• how the SSA is measured and whether the measurement is aligned with the patent’s understood method.

Is SSA “about” a meaningful wiggle room?

Claims include both:

• exact numeric boundaries in some instances (“1.3 to 3.1” appears as non-“about” in claim 11 text you provided), and
• “about” ranges in other claims (1.2–3.6; 1.3–3.1).

“About” typically allows minor deviations, but the allowable deviation is claim-construction dependent and often contested with expert evidence. Commercial risk management should treat “about” as still requiring SSA to land near the stated band, not far outside it.

Which claims are strongest for litigation: composition vs method, and broadest vs narrowest ranges?

Composition claims (1, 2, 3) are typically the highest-leverage

They cover the product itself:

• solid pharmaceutical composition
• dosage-unit medicament
• explicit dosage forms

If an accused SR nifedipine product sells into the US market in a matching dosage form, the composition claims provide the primary infringement pathway.

Method claims (4, 8, 12) are narrower in practice but can extend coverage

Method claims can reach:

• cases where composition claims are structurally disputed (e.g., solid diluent definition or composition composition differences),
• but the product still employs the claimed SSA crystals and is marketed/used for hypertension with SR effect.

In enforcement, method claims often require stronger linkage evidence: prescribing patterns, labeling, and SR performance.

SSA breadth determines which claims “catch” the accused product

• If the accused SSA is within 1.0–4 m²/g, claim 1 is in play.
• If SSA is within 1.2–3.6 m²/g, claims 5–6–7 are in play.
• If SSA is within 1.3–3.1 m²/g, claims 9–10–11 and related method claims are in play.

From a risk perspective, claim 1 is the broadest and therefore the “default” anchor; narrower dependent claims become important when SSA is close to edges or measurement variability is argued.

What is the patent’s likely claim construction focus in US courts?

1) Meaning of “specific surface area”

Key questions in litigation usually include:

• definition of SSA metric (common in the industry: BET surface area),
• sample preparation,
• measurement conditions and repeatability,
• whether the SSA is measured on the nifedipine crystals before blending, or after formulation.

Because the claim text ties SSA to “nifedipine crystals,” it implies measurement on the crystals, but the infringement analysis may still consider effective SSA in the administered product depending on proof strategy.

2) Meaning of “sustained release”

Outcome language invites:

• dissolution profiling arguments,
• comparison to SR definitions under pharmacopeial or regulatory frameworks,
• reliance on in vitro dissolution and in vivo correlation where available.

Even if the formulation is designed for SR using excipients like polymers or matrices, the claim still requires the SR result. A defendant may argue lack of SR under test conditions, or that their SR behavior arises from other formulation mechanisms without relying on the SSA-defined crystals.

3) Scope of “solid diluent”

If the patent specification defines solid diluent narrowly, that could cabin claim scope. If not, “solid diluent” is likely interpreted broadly to include standard solid excipients used to form tablets, capsules, and similar dosage forms.

How does US 5,264,446 compare with typical nifedipine SR patent families (what is likely novel here)?

Most nifedipine SR patents historically focus on:

• matrices (hydrophilic/hydrophobic polymers),
• osmotic delivery,
• coating systems,
• microencapsulation,
• layered tablets or multiparticulates.

US 5,264,446 differentiator: Instead of claiming a specific release mechanism (polymer type, coating thickness, osmotic membrane, or GI residence design), it claims a material attribute (SSA of nifedipine crystals) that is presumed to drive SR behavior.

That structural shift matters because it can:

• broaden potential overlap with existing SR technologies that also use controlled particle properties, and
• narrow overlap where a competing product uses different SSA but otherwise matches coating/matrix systems.

What patent estate risks exist for competing SR nifedipine products?

Without additional patent numbers, parties, or the patent’s bibliographic data and prosecution history, the landscape cannot be mapped reliably. Under your constraint, no additional patent crawling or Orange Book cross-referencing is possible from the claim text alone.

That said, the infringement-risk logic is straightforward:

High risk scenario

An SR nifedipine product in any covered dosage form uses nifedipine crystals whose SSA falls within 1.0–4 m²/g, and the formulation uses a solid diluent and produces SR release.

Moderate risk scenario

SSA is inside the broad range but the formulation’s SR behavior is challenged, or diluent definition is disputed.

Lower risk scenario

SSA is demonstrably outside 1.0–4 m²/g, or the product uses crystals with different physical characteristics that shift SSA materially.

Key Takeaways

• US 5,264,446 is an SSA-driven nifedipine SR patent with numeric crystal surface-area ranges as the central claim limitation.
• Claim coverage spans multiple solid dosage forms and includes both product (composition/medicament) and use (hypertension SR administration) claims.
• Litigation will likely focus on SSA definition and testing, sustained-release proof under relevant conditions, and whether the accused formulation satisfies “solid diluent” and SR limitations.
• The broadest claim anchor is SSA 1.0–4 m²/g; narrower ranges create layered protection for products whose SSA falls near the middle of the claimed bands.
• Design-around risk is highest when competing SR products use controlled crystal processing that yields SSA within the claimed windows.

FAQs

1) Does US 5,264,446 cover only oral nifedipine products?

No. The claims expressly include tablets, pills, dragees, capsules, suppositories, sachets, and two-layer tablets, as long as SSA and solid-diluent limitations are met.

2) Are “about” SSA ranges in the claims a complete safe harbor for near-miss products?

No. “About” introduces interpretive flexibility, but infringement still turns on whether measured SSA lands within the legally construed range, typically contested with expert measurement evidence.

3) Can a defendant argue they meet SR without relying on SSA?

They can argue that sustained release arises from other formulation mechanisms; however, the claim requires that the specified SSA crystals are used “to result in sustained release,” so sustained-release evidence and claim construction remain pivotal.

4) What is the most important measurable parameter for infringement?

The nifedipine crystal specific surface area and how it is measured for the crystals used in the accused product.

5) Could the method claims expand risk beyond composition claims?

Yes. If composition claims are challenged, method claims can still apply when hypertension treatment involves administering the defined SSA nifedipine crystals in a solid-diluent SR regimen.

References

1. Provided claim text (user-supplied) for US Patent 5,264,446 (nifedipine SSA 1.0–4 m²/g; “about” 1.2–3.6 m²/g; “about”/1.3–3.1 m²/g; solid diluent; sustained release; hypertension method claims).

Drugs Protected by US Patent 5,264,446

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

Foreign Priority and PCT Information for Patent: 5,264,446

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3033919	Sep 09, 1980

International Family Members for US Patent 5,264,446

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	226377
Austria	5761
Australia	558331