Details for Patent: 4,753,802

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Summary for Patent: 4,753,802

Title:	Verapamil dosage form
Abstract:	An osmotic dosage form comprising verapamil and mannitol in a nonequilibrium ratio.
Inventor(s):	Sally I. Stephens, L. G. Hamel
Assignee:	Alza Corp
Application Number:	US06/841,144
Patent Claim Types: see list of patent claims	Composition; Delivery; Dosage form;

Scope, Claims, and Patent Landscape Analysis for US Patent 4,753,802 (Verapamil Dosage Form)

What is US 4,753,802 claiming in technical and functional terms?

US 4,753,802 claims a controlled-release dosage form built around a cellulose acylate wall that is:

• Permeable to fluid
• Impermeable to verapamil
• Surrounds a drug compartment
• Includes at least one passageway that allows drug release over time into the outside environment

The dosage form’s release is enabled by a combination of (i) a semi-permeable membrane wall and (ii) a structured passageway path that governs egress of verapamil from the compartment.

The independent claim 1 also adds a specific internal formulation constraint: the compartment contains verapamil with mannitol in a non-equilibrium ratio of 0.9 to 1.1.

The scope is therefore not just “verapamil in a controlled-release device.” It is a narrow construction that requires all of these elements together:

1. cellulose acylate membrane wall (with permeability/impermeability properties)
2. drug compartment
3. verapamil + mannitol in a constrained nonequilibrium ratio (0.9 to 1.1)
4. at least one passageway in the wall
5. verapamil release to the environment of use over time
6. specific embodiment options for salt form, acetyl content of cellulose acetate, and dose range
7. GI/oral adaptation limitation in claim 11

How does claim 1 define the core invention (scope anchors)?

Claim 1 is the sole independent claim and defines the invention’s critical technical anchors:

Structural requirements

• Dosage form for delivering verapamil to a biological environment
• A wall comprising a cellulose acylate, including:
  • “permeable to the passage of fluid”
  • “impermeable to the passage of verapamil”
• The wall surrounds and forms a compartment
• A dosage amount of verapamil located in the compartment
• The wall has at least one passageway connecting the compartment to the exterior, for dispensing “over time”

Composition requirement (internal formulation constraint)

• Verapamil in the compartment is present with mannitol in a nonequilibrium ratio of 0.9 to 1.1

Functional requirement

• The passageway enables dispensing “to the environment of use over time”
• The membrane blocks verapamil while allowing fluid ingress, which supports sustained delivery

Impact on scope: any competitor design that lacks the cellulose acylate wall with the specified permeability/impermeability profile, lacks a compartment, omits mannitol verapamil nonequilibrium ratio constraint, or removes passageways fails to stay within claim 1.

What do dependent claims add (coverage, narrowing, and design-for-infringement levers)?

Dependent claims define narrower variants that increase clarity for manufacturing targets.

Salt form variants

• Claim 2: verapamil is a therapeutically acceptable addition salt
• Claim 3: verapamil is specifically verapamil hydrochloride

Scope effect: claim 2 captures any acceptable salt; claim 3 targets the hydrochloride form.

Cellulose acetate acetyl content variants (membrane spec)

• Claim 4: cellulose acetate acetyl content = 39.8%
• Claim 5: cellulose acetate acetyl content = 32%
• Claim 6: wall composition comprises both acetyl-content fractions: 39.8% and 32%

Scope effect: the claims are not generic “cellulose acetate.” They are tied to specific acetylation degrees that control membrane properties.

Nonequilibrium ratio refinement

• Claim 7: nonequilibrium ratio is 1 (the center of the 0.9 to 1.1 band in claim 1)

Scope effect: claim 7 captures embodiments at the midpoint, but the broader range remains claim 1.

Dose amount ranges

• Claim 8: dosage form comprises 50 to 600 mg of verapamil
• Claim 9: 115 to 125 mg of verapamil pharmaceutically acceptable salt
• Claim 10: 235 to 245 mg of verapamil pharmaceutically acceptable salt

Scope effect: these provide explicit commercial-target ranges. If a product dose falls outside these ranges, it may still be within claim 1 unless dose amount is treated as a limitation (it is, but claim 1 as provided does not include a numerical dose range). In practice, claim 8-10 define narrower embodiments.

Route and site adaptation

• Claim 11: environment is the gastrointestinal tract; dosage form is adapted for oral admittance

Scope effect: locks the use case to oral GI delivery for claim 11 only. Claim 1 remains broader as “biological environment,” but in a landscape analysis claim 11 maps strongly to practical oral products.

What is the likely claim construction logic (how infringement would be assessed)?

Given the claim language, an infringement analysis would typically decompose the claim into required elements and map accused products to each:

• Wall material: must be cellulose acylate; dependent claims further require cellulose acetate with specified acetyl content.
• Permeability/impermeability: wall must permit fluid movement while preventing verapamil passage through the wall (drug stays in the compartment until it reaches the passageway path).
• Compartment structure: presence of a bounded compartment surrounded by the membrane.
• Passageway: at least one passageway in the wall connecting compartment interior to exterior.
• Verapamil-mannitol nonequilibrium ratio: accused formulation must meet a ratio range of 0.9 to 1.1 (or 1 for claim 7).
• Salt identity: if challenged under claim 3, verapamil must be verapamil hydrochloride; under claim 2 it must be a therapeutically acceptable addition salt.
• Dose and GI adaptation: asserted under claims 8-11 depending on product specifics.

A product that changes the mechanism, such as replacing the cellulose acylate wall with a different polymer matrix that permits verapamil through the wall, would typically fall outside the core limitation.

How would the claims map to typical product architectures?

Architecture that fits best

• A membrane-coated unit or micro-encapsulated compartment:
  • cellulose acetate/acylate wall
  • fluid ingress
  • minimal drug passage through membrane body
  • micro-channels or passageways for drug egress

Architecture that is at risk of falling outside

• Reservoir devices without cellulose acylate (different polymer family)
• Systems where verapamil diffuses through the wall without a passageway limitation
• Solid dosage forms without a distinct compartment surrounded by a cellulose acylate wall
• Reservoir systems without mannitol or without meeting the specified verapamil-mannitol nonequilibrium ratio
• Systems that do not meet the specified acetyl content when litigating dependent claims 4-6

Patent landscape: what nearby patent themes would likely overlap

This patent is positioned at the intersection of:

1. controlled-release verapamil (oral, GI delivery)
2. membrane and passageway-based diffusion control
3. cellulose acetate/cellulose acylate membrane parameterization
4. verapamil solid-state and formulation modulation using mannitol to achieve a release-driving nonequilibrium ratio

Given that, the landscape for US patents around this date would typically include competitors and follow-on applicants pursuing:

• verapamil controlled-release oral dosage forms (matrix, beads, coated reservoirs)
• cellulose-based or polymer film membranes
• channelized or perforated membrane-controlled release
• salt form and dosing range optimization
• excipient selection impacting dissolution rate and release kinetics

However, a precise “who-owns-what” map for specific US family members and citations cannot be produced from the information provided. The claim text alone does not identify inventors, assignees, filing date, priority, or the patent’s cited references needed to assemble a complete landscape.

Where are the main competitive entry points within the claim scope?

The claims create three entry points that a design-to-avoid strategy would target, and three entry points that a design-to-infringe strategy would use.

Claim elements most likely to be engineered for avoidance

• Cellulose acylate wall selection: substituting away from cellulose acetate/acylate, or using an acylate not meeting the acetyl-content ranges in dependent claims.
• Passageway architecture: removing passageways or using a release mechanism that does not rely on passageways in the wall.
• Mannitol + nonequilibrium ratio: eliminating mannitol or altering the nonequilibrium ratio outside 0.9 to 1.1.

Claim elements most likely to be engineered for capture

• Using cellulose acetate acylate walls with acetyl content tuned to 39.8% and/or 32%.
• Implementing fluid-permeable/drug-impermeable membrane behavior with passageways.
• Formulating verapamil + mannitol so that measured nonequilibrium ratio lands within 0.9 to 1.1, and optionally exactly 1.

What is the practical freedom space: claims that are narrow versus claims that are broad?

• Broadest core (claim 1): the mechanism and internal formulation ratio are both required, but the dose and salt form are not numerically limited in claim 1 as provided. The “biological environment” is broader than GI/oral in claim 11.
• Narrowest (dependent claims):
  • acetyl content values (claims 4-6)
  • salt type (claim 3, and general salt in claim 2)
  • nonequilibrium ratio equals 1 (claim 7)
  • specific dose ranges (claims 8-10)
  • oral GI adaptation (claim 11)

From a portfolio standpoint, a competitor could potentially design a controlled-release verapamil product that matches claim 1 architecture but selects a different salt form or dose range, avoiding dependent-claim assertions while still leaving risk under claim 1.

Key Takeaways

• US 4,753,802 claims a cellulose acylate membrane reservoir with a drug compartment, where the membrane is fluid-permeable and verapamil-impermeable, and passageways control release over time.
• The invention’s internal formulation constraint is verapamil + mannitol in a nonequilibrium ratio of 0.9 to 1.1 (with a narrower midpoint in claim 7).
• Dependent claims narrow protection to verapamil salt forms, cellulose acetate acetyl contents (39.8% and/or 32%), specific dose ranges, and oral GI delivery.
• For landscape and enforcement: the most determinative limitations to map are the membrane material and acetyl content, the presence and role of passageways, and the verapamil-mannitol nonequilibrium ratio.

FAQs

1) Does claim 1 require a specific verapamil salt?
No. Claim 1 requires verapamil in the compartment; salt form limitations appear in dependent claims 2 and 3.

2) Is the passageway requirement mandatory?
Yes. Claim 1 requires “at least one passageway in the wall connecting the compartment with the exterior.”

3) Are cellulose acylate acetylation levels required for infringement?
For claim 1, it requires “cellulose acylate.” For claims 4-6, the wall must be cellulose acetate with acetyl content at 39.8%, 32%, or both in the specified combination.

4) What happens if the verapamil-mannitol ratio is outside 0.9 to 1.1?
The product would not meet claim 1’s nonequilibrium ratio limitation as written.

5) Is oral GI delivery required?
Not in claim 1 as provided. Oral GI limitation appears in dependent claim 11.

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References

[1] US Patent 4,753,802, “Dosage form for delivering verapamil” (claims as provided in prompt).

Drugs Protected by US Patent 4,753,802

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

International Family Members for US Patent 4,753,802

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	59549
Australia	587307
Australia	6871587