Details for Patent: 5,439,689

« Back to Dashboard

Summary for Patent: 5,439,689

Title:	Diltiazem formulation
Abstract:	The present invention is directed to a diltiazem formulation suitable for one a day administration. The formulation contains a blend of diltiazem beads having two differing dissolution profiles.
Inventor(s):	Dennis L. Hendrickson, Dan C. Dimmitt, Mark S. Williams, Paul F. Skultety, Michael J. Baltezor
Assignee:	Valeant International Bermuda
Application Number:	US08/164,062
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device; Dosage form;

United States Patent 5,439,689 (Diltiazem Once-Daily Rapid/Delayed Release): Claim Scope, Patent Estate Map, Expiration Drivers, and Generic/FDA Entry Risks

Executive summary: U.S. Patent 5,439,689 claims an oral diltiazem regimen that combines (i) a rapid-release component and (ii) a delayed-release component built from polymer-coated diltiazem cores engineered to meet specific USP paddle dissolution profiles in 0.1N HCl (37°C, 100 rpm). Claim scope is unusually tight on dissolution windows, polymeric coating identity/composition, and polymer-plasticizer parameters. The strongest enforcement leverage comes from: (1) proving the accused product hits the claimed release percent bands at specified times, and (2) showing the coating matches the claimed polymerized acrylate copolymer system (ethyl acrylate/methyl methacrylate with quaternary trimethylammoniumethyl methacrylate at defined ratios) and plasticizer package.

---

What does U.S. Patent 5,439,689 claim for once-daily diltiazem in the US?

Core claim 1 scope: “rapid + delayed” two-component architecture

Claim 1 is a method of treating cardiovascular disorders using a once-a-day oral diltiazem formulation that comprises two distinct components with different dissolution-delay behavior in 0.1N HCl under USP XXII type 2 paddle (37°C, 100 rpm).

1. Rapid release component (A)

• Contains a diltiazem core (diltiazem or pharmaceutically acceptable salt, optional excipients).
• The core is substantially enveloped by a first polymeric coating material such that total diltiazem release meets:
  • 0–40% release after 3 hours
  • 30–100% release after 6 hours

2. Delayed release component (B)

• Contains a diltiazem core (diltiazem or salt, optional excipients).
• The core is substantially enveloped by a second polymeric coating material such that release meets first-stage bounds:
  • 0–45% release after 12 hours
  • 0–75% release after 18 hours
  • ≥40% release after 24 hours
• Claim 1 then adds an additional overall dissolution pattern constraint for the formulation:
  • 20–45% after 6 hours
  • 25–50% after 12 hours
  • 35–70% after 18 hours
  • ≥70% after 24 hours
  • ≥85% after 30 hours

Treatment purpose is broad; product definition is narrow

“Cardiovascular disorders” covers wide therapeutic indications, but claim 1 narrows the infringement hooks to product structure + dissolution behavior.

Key practical impact: infringement is not based on “diltiazem SR” generically; it depends on whether the accused dosage form reproduces the claimed release-time bands in the specified test system.

---

How do dependent claims narrow the polymeric coating chemistry and plasticizer system?

Claims 2–9: delayed component coating composition ranges

Claim 2:

• Second polymeric coating contains 10–75 w/w% polymerized acrylate (based on total weight of the delayed release component).

Claim 3:

• The second polymeric coating comprises 15–50 w/w% of the delayed release component.

Claim 4:

• Polymerized acrylate is specifically an ethyl acrylate / methyl methacrylate copolymer containing trimethylammoniumethyl methacrylate at about 1:40 relative to neutral monomers.

Claim 5:

• Coating contains 5–15 w/w% plasticizer (based on total weight of the polymeric coating).

Claim 6:

• Plasticizer is tributyl citrate and acetyl tributyl citrate.

Claim 7:

• Second polymeric coating is about 25 w/w% of the delayed release component.

Claim 8:

• Polymer system is a binary copolymer blend:
  • copolymer a) ethyl acrylate + methyl methacrylate with trimethylammoniumethyl methacrylate at about 1:40
  • copolymer b) ethyl acrylate + methyl methacrylate with trimethylammoniumethyl methacrylate at about 1:20
  • a:b ratio = 95:5

Claim 9:

• Adds an additional delayed component dissolution profile in 0.1N HCl:
  • 0–5% after 6 hours
  • 0–10% after 12 hours
  • 0–35% after 18 hours
  • 50–90% after 24 hours

Claims 10–12: rapid component coating chemistry and coating loading

Claim 10:

• Rapid release component dissolution:
  • 0–20% after 3 hours
  • ≥50% after 6 hours

Claim 11:

• Rapid component coating polymer matches the same type of quaternary methacrylate copolymer system as claim 8 (1:40 and 1:20 blend; 95:5 ratio).

Claim 12:

• First polymeric coating comprises 10–15 w/w% of the total weight of the rapid release component.

Claim 13: overall formulation dissolution tighter “combined product” envelope

Claim 13 specifies overall dissolution at later points:

• 25–40% after 6 hours
• 30–45% after 12 hours
• 40–65% after 18 hours
• ≥75% after 24 hours

Claim 22: alternative delayed component dissolution profile

Claim 22 provides a different delayed profile window:

• 0–15% after 12 hours
• 0–45% after 18 hours
• ≥45% after 24 hours

Key practical impact: dependent claims constrain not only dissolution but the exact polymer composition and plasticizer identity. A product can be engineered to meet the general release-time windows but still avoid narrower dependent claims by altering:

• polymerized acrylate identity (quaternary methacrylate level or monomer choices),
• polymer blend ratio (95:5),
• plasticizer selection (or absence of the tributyl/acetyl tributyl citrate system), or
• coating fraction and coating loading.

---

What does claim 14 cover: isolated delayed-release diltiazem formulation vs combined method?

Claim 14 moves from a two-component method to a single delayed-release diltiazem formulation.

Claim 14 delayed-release dissolution target

A central core surrounded by polymeric coating such that total diltiazem release in 0.1N HCl is:

• 0–5% after 12 hours
• 0–20% after 18 hours
• 50–90% after 24 hours
• 80–100% after 30 hours

Claims 15–21: delayed formulation chemistry mirrors the method’s dependent claims

• Claim 15: coating contains 10–75 w/w% polymerized acrylate
• Claim 16: coating comprises 15–50 w/w% of formulation
• Claim 17: polymerized acrylate is ethyl acrylate + methyl methacrylate copolymer with trimethylammoniumethyl methacrylate about 1:40
• Claim 18: plasticizer 5–15 w/w% of polymer coating
• Claim 19: plasticizer is tributyl citrate and acetyl tributyl citrate
• Claim 20: polymeric coating about 25 w/w% of formulation
• Claim 21: polymer blend again with 1:40 vs 1:20 quaternary methacrylate levels, 95:5 ratio

Key practical impact: claim 14 is the cleanest independent “formulation-only” hook for enforcement in delayed-release diltiazem products that match the specific dissolution profile in gastric-like media.

---

Where are the infringement fault lines: dissolution testing, unit operations, and “component” matching?

1) Dissolution apparatus/test conditions are claim-embedded

Claims specify:

• USP XXII type 2 paddle
• 37°C
• 0.1N HCl
• 100 rpm

Any validity or infringement strategy will turn on whether the accused product’s dissolution can be mapped to the claim bands under the same (or substantially equivalent) conditions.

2) “Substantially envelops” leaves room on morphology but not function

“Substantially envelops” is a structural descriptor, but the claims heavily functionally define outcomes through dissolution percentages. Expect the decisive dispute to be performance alignment rather than microscopic coating continuity.

3) Two-component claim 1 adds a “combined formulation” performance constraint

Claim 1 requires not only that each component hits its own dissolution window, but also that the overall formulation hits the additional pattern at 6/12/18/24/30 hours. A product could potentially match one component’s window while missing the overall release choreography.

---

What is the likely patent landscape posture around 5,439,689 for US diltiazem once-daily products?

How to treat this patent in an estate map

U.S. 5,439,689 is an older composition/method patent built around:

• a dual-release architecture
• polymeric coat chemistry using quaternary methacrylate-bearing acrylate copolymers
• a specific plasticizer system
• hard USP dissolution performance windows

In a real-world freedom-to-operate (FTO) landscape, this kind of claim tends to sit in a cluster with:

• other patents covering matrix vs coated bead vs multiparticulate architectures,
• other patents covering specific polymer compositions or layered coating systems,
• patents covering process steps for coating and encapsulation (if present in the family),
• and later generation patents claiming alternative dissolution profiles or alternative polymer blends.

Actionable interpretation: the strongest risk is from products that keep the same dissolution schedule and polymer/plasticizer chemistry. If an entrant changes the coating polymer system while keeping the release-time profile, it may avoid dependent claim coverage while still potentially implicating broader claim 1 architecture if overall release bands match.

---

When does exclusivity end and what does “patent life” imply for 5,439,689?

No enforceable exclusivity timeline can be produced from the claim text alone. A complete expiration analysis requires the patent filing date, issue date, any terminal disclaimers, maintenance status, and any adjustment. Under the operating constraints here, no such data is provided, so no expiration date can be stated.

What can be said from claim structure:

• The patent is a classic composition/method patent with heavy formulation performance parameters. If it is expired, enforcement risk shifts to trade dress, formulation trade secrets, FDA sameness/differences, and other overlapping patents in the same technical area.

---

What would a generic or follow-on product need to avoid to reduce literal infringement risk?

Avoiding dependent claims (2–12, 15–21)

A formulator can reduce risk by moving outside at least one of these claim-anchored constraints:

• Polymerized acrylate loading: avoid 10–75 w/w% (delayed component and formulation coatings).
• Coating fraction: avoid 15–50 w/w% (and avoid the “about 25 w/w%” target).
• Polymer chemistry: avoid the specific quaternary methacrylate-bearing acrylate copolymer structure with the 1:40 and 1:20 ratios and especially the 95:5 blend.
• Plasticizer identity: avoid the specific tributyl citrate and acetyl tributyl citrate system.
• Plasticizer loading: avoid 5–15 w/w% plasticizer.
• Rapid and delayed dissolution bands: tune release to fall outside the relevant percent windows at the specified time points.

Avoiding claim 1 (method with combined performance)

Even if dependent chemistry is avoided, claim 1 can still be implicated if:

• the product still has a rapid+delayed multipart system, and
• the rapid and delayed coatings achieve the claimed release windows, and
• the overall formulation dissolution profile hits the 6/12/18/24/30-hour bounds.

Net: the easiest “escape hatch” for a challenger is often changing polymer chemistry and plasticizer package, then engineering the multipart release to meet an alternative schedule that does not overlap the narrow claim bands. The more the product’s dissolution curve aligns with the claim windows, the less chemistry matters.

---

How strong is the patent for litigation based on claim specificity?

Strength indicators

• The claims define quantitative, time-anchored release percentages in a named medium and apparatus.
• The dependent claims narrow down polymer composition, polymer blend ratio, and plasticizer identity.
• The claims include both:
  • multipart formulation performance (claim 1), and
  • isolated delayed-release formulation performance (claims 14–21).

Weakness indicators (attack surfaces)

• Heavy reliance on dissolution testing increases the importance of:
  • test method mapping,
  • batch-to-batch variability,
  • and statistical reproducibility.
• If an accused product uses different coating chemistry but still hits similar dissolution windows, infringement may hinge on whether the accused structure still falls within the “polymeric coating material” definitions of the relevant claims (particularly for claim 1, which is less explicit on polymer identity than dependent claims).

Net litigation posture: claim 1 provides a broad functional hook via release windows; dependent claims provide high-specificity chemical and composition hooks that can either strengthen enforcement or be easily escaped by formulation redesign.

---

Key references within the claim set: “hot spots” for claim charting

The following elements should be the center of any infringement/invalidity chart for 5,439,689:

• USP dissolution parameters: type 2 paddle, USP XXII, 37°C, 0.1N HCl, 100 rpm.
• Rapid component release windows:
  • claim 1: 0–40% at 3 hours; 30–100% at 6 hours
  • claim 10: 0–20% at 3 hours; ≥50% at 6 hours
• Delayed component release windows:
  • claim 1: 0–45% at 12 hours; 0–75% at 18 hours; ≥40% at 24 hours
  • claim 9: 0–5% at 6 hours; 0–10% at 12 hours; 0–35% at 18 hours; 50–90% at 24 hours
  • claim 22: 0–15% at 12 hours; 0–45% at 18 hours; ≥45% at 24 hours
• Overall formulation release windows (claim 1):
  • 20–45% at 6 hours; 25–50% at 12 hours; 35–70% at 18 hours; ≥70% at 24 hours; ≥85% at 30 hours
• Polymerized acrylate content and coating weight fractions:
  • claim 2: 10–75 w/w%
  • claim 3: 15–50 w/w%
  • claim 7/20: about 25 w/w%
• Quaternary methacrylate-bearing copolymer blend (claim 8/21):
  • a) trimethylammoniumethyl methacrylate at 1:40
  • b) trimethylammoniumethyl methacrylate at 1:20
  • a:b = 95:5
• Plasticizer identity and loading:
  • claim 5: 5–15 w/w% plasticizer
  • claim 6/19: tributyl citrate + acetyl tributyl citrate

---

Key Takeaways

• U.S. Patent 5,439,689 is built around a dual-release once-daily diltiazem system with USP type 2 paddle dissolution windows in 0.1N HCl as the main functional infringement driver.
• Dependent claims 2–12 and 15–21 tightly constrain polymerized acrylate composition (ethyl acrylate/methyl methacrylate with quaternary trimethylammoniumethyl methacrylate at defined ratios), blend ratio (95:5), plasticizer identity (tributyl citrate and acetyl tributyl citrate), and loading/coating fractions.
• The most litigation-ready claim elements for claim charts are the time-point release percentage bands and the polymer/plasticizer identity parameters.
• Designing around the patent typically requires breaking at least one of:
  • the rapid/delayed release choreography at the specified hours,
  • the overall formulation dissolution pattern,
  • the polymer chemistry/blend ratio, and/or
  • the plasticizer system.

---

FAQs

1. How does claim 1 differ from claim 14 in enforcement focus for diltiazem products?
   Claim 1 ties infringement to a two-component architecture plus an overall formulation dissolution schedule; claim 14 targets a delayed-release single formulation dissolution pattern.

2. Which polymer parameters are most critical to avoid dependent claim coverage (claims 4, 8, 11, 17, 21)?
   The quaternary trimethylammoniumethyl methacrylate level (1:40 vs 1:20) and the 95:5 copolymer blend ratio.

3. What are the key delayed-component dissolution time points in 0.1N HCl for claim charting?
   12 hours, 18 hours, and 24 hours (with additional constraints at 6 hours in claim 9).

4. How do the rapid-release dissolution windows in claims 1 and 10 interact during design-around?
   A product must remain within or outside the claimed 3-hour and 6-hour release bands for the rapid component, while also satisfying the combined formulation windows for claim 1.

5. What design changes most directly reduce risk while keeping once-daily dosing?
   Switching the coating polymer chemistry away from the specified quaternary methacrylate copolymer blend and/or changing plasticizer identity/loading, then retuning dissolution so it falls outside the claimed release envelopes.

---

References

1. United States Patent 5,439,689. (Claims text provided in user prompt).

Drugs Protected by US Patent 5,439,689

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 5,439,689

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	147982
Australia	1632692
Australia	653223
Canada	2068980