Details for Patent: 6,979,463

Summary for Patent: 6,979,463

Title:	Stable extended release oral dosage composition
Abstract:	A film-coated extended release solid oral dosage composition containing a nasal decongestant, pseudoephedrine or salt thereof, e.g., pseudoephedrine sulfate in a core effective to provide a geometric maximum plasma concentration of pseudoephedrine of about 345 ng/mL to about 365 ng/mL at a time of about 7.60 hrs to about 8.40 hrs and having two or three film-coatings on the core, the second one containing an amount of the non-sedating antihistamine, desloratadine, effective to provide a geometric maximum plasma concentration of desloratadine of about 2.15 ng/mL to about 2.45 ng/mL at a time of about 4.0 hours to about 4.5 hours, and use of the composition for treating patients showing the signs and symptoms associated with allergic and/or inflammatory conditions of the skin and airway passages are disclosed.
Inventor(s):	Jim H. Kou
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US10/175,460
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Executive summary
US Patent 6,979,463 claims an extended-release (ER) solid oral, multi-layer coated composition combining pseudoephedrine (or pharmaceutically acceptable salt) and desloratadine (with associated 3-hydroxydesloratadine exposure). The claims are unusually specific: they lock in (i) ER plasma concentration windows for pseudoephedrine and desloratadine after single-dose and steady-state dosing, (ii) a defined coated architecture (core plus first swellable polymer-based film layer plus desloratadine second film layer, optionally a third dye layer), (iii) coating polymer classes and excipient functions (water-swellable film-forming neutral or cationic copolymeric ester, film modifier, lubricant; plus defined water-soluble film modifiers and optional anti-foaming), and (iv) formulation performance constraints (degradation product limits; dissolution of both pseudoephedrine sulfate and desloratadine). The patent’s value for enforcement and freedom-to-operate turns on whether a competitor’s product matches the same exposure targets and coating system, not merely the same two actives.

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How broad are the claims in US Patent 6,979,463 for pseudoephedrine plus desloratadine extended release?

The claim set spans three layers of claim narrowing:

1. Product architecture (structural): ER solid oral dosage with (a) a pseudoephedrine-containing core, (b) a first coating with a water-swellable film-forming neutral or cationic copolymeric ester plus film modifier and lubricant, and (c) a second coating containing desloratadine. Optional third coating with dye and similar coating excipients appears in dependent claim 6.
2. Exposures as functional limits (quantitative, pharmacokinetic): Claims repeatedly require geometric mean or maximum plasma concentration windows and timing ranges after single-dose and after steady-state daily dosing.
3. Formulation performance and stability limits (quantitative): Dependent claims impose dissolution behavior and degradation product thresholds (desloratadine degradation products including N-methyldesloratadine and N-formyldesloratadine; pseudoephedrine degradation products).

Core claim logic: what must be true for infringement

To infringe independent claim 1, an accused ER tablet/caplet must satisfy all of the following, as claimed:

• ER solid oral composition with a pseudoephedrine core (salt allowed).
• First coating over the core containing:
  • water-swellable film-forming neutral or cationic copolymeric ester,
  • film modifier,
  • lubricant.
• Second coating over first coating containing desloratadine.
• Pseudoephedrine PK window (single dose): geometric maximum plasma concentration (Cmax) of pseudoephedrine about 345–365 ng/mL at about 7.60–8.40 hours post-dose.
• Desloratadine PK window (single dose): geometric maximum plasma concentration of desloratadine about 2.10–2.45 ng/mL at about 4.0–4.5 hours post-dose.

This is not a “composition comprising” broad claim. It is a composition plus specific in vivo performance characteristics.

How dependent claims expand and narrow the scope

• Claim 2 narrows desloratadine metabolites/exposure: requires 3-hydroxydesloratadine Cmax around 0.75–1.15 ng/mL at 5.50–6.25 hours.
• Claims 3–4 narrow to matrix core and uniform coatings; claim 4 also lists specific coating components and optional anti-foaming agent.
• Claims 9–12 narrow by dose amounts and degradation product acceptance windows.
• Claims 13–16 narrow by specific excipient ingredient ranges and polymer/lubricant choices (including ethyl acrylate/methyl acrylate neutral copolymer; PEG 200–8000; optional methyl siloxane polymer + silica; optional dye).
• Claims 17 narrows to a dissolution profile benchmark: >90% desloratadine dissolves in 45 minutes in 0.1N HCl; and >90% pseudoephedrine sulfate dissolves over 16 hours in phosphate buffer after initial HCl.
• Claims 18–28 narrow by steady-state daily dosing PK windows and exposure metrics (Cmax windows, Cmin windows, and AUC ranges for parent and metabolite).
• Claims 29–32 are method-of-use claims tethered to administering “an effective amount of the extended release solid composition of claim 1” for airway conditions, nasal congestion, urticaria, and allergic rhinitis.

Practical effect: infringement requires PK and formulation match, not just content match

Even if a competitor uses pseudoephedrine + desloratadine in a two-layer ER tablet, if its PK profile shifts outside the claimed windows (timing and concentration ranges), it may fall outside these claims.

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What specific claim elements drive enforceability in US 6,979,463?

1) Two-layer coating system with swellable polymer film-formers

Independent claim 1 ties infringement to:

• a water-swellable film-forming neutral or cationic copolymeric ester in the first coating, and
• desloratadine presented in a second coating over that first film.

Dependent claims define typical polymer families in more concrete terms:

• Neutral copolymer of ethyl acrylate and methyl acrylate (claims 14 and 15 and 16).
• First and second coating both include film modifier and lubricant elements, with second coating also including a water-soluble film modifier (claim 4 / 15 / 16).

2) Explicit PK Cmax and timing windows

The patent repeatedly claims geometric Cmax and geometric steady-state Cmax/Cmin with timing constraints.

• Claim 1 (single dose):

  • pseudoephedrine Cmax 345–365 ng/mL at 7.60–8.40 h
  • desloratadine Cmax 2.10–2.45 ng/mL at 4.0–4.5 h

• Claim 18 (steady-state daily dosing):

  • pseudoephedrine Cmax 382–664 ng/mL at 5.25–7.99 h after ≥10 days
  • desloratadine Cmax 1.59–3.39 ng/mL at 2.24–5.12 h after ≥12 days

• Claims 25–28 add steady-state Cmin windows and 3-hydroxydesloratadine Cmin/Cmax windows.

• Claims 20–24 include AUC exposure bands for both desloratadine and 3-hydroxydesloratadine and pseudoephedrine.

This kind of “PK-locked” claim is enforceable but typically makes litigation hinge on comparative bioequivalence/bioavailability studies, expert interpretation of geometric means, and mapping test conditions to the patent’s dosing regimen.

3) Degradation product limits and stability constraints

Claims 9–12 require:

• Total desloratadine degradation products ≤ about 2.0% by weight (claim 9).
• Specific thresholds for:
  • N-methyldesloratadine 0.3–0.4% by weight (claim 10)
  • N-formyldesloratadine 0.4–0.5% by weight (claim 10)
• Additional caps:
  • total desloratadine degradation products ≤ about 0.8–1.0 wt% (claim 11)
  • pseudoephedrine degradation products < about 0.5 to no more than about 1.1 wt% (claim 12)

If a competitor’s formulation generates higher degradation products or uses different stabilization, it may not meet these dependent claim limitations, even if its PK is similar.

4) Dissolution system as performance evidence

Claim 17 adds a dissolution test regime:

• desloratadine: >90% dissolves into stirred 0.1N HCl at 37°C in about 45 minutes
• pseudoephedrine sulfate: >90% dissolves in 0.1N HCl in first hour, then continues in phosphate buffer pH 7.5 at 37°C over 16 hours

These are testable endpoints. An accused product’s dissolution method and results can become a direct claim map issue.

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What formulations are protected by this patent (ingredient ranges, polymer types, and coatings)?

A. Dose-level formulation constraints

A representative narrow embodiment appears in claim 9 and 17:

• core: about 240 mg pseudoephedrine (or salt)
• second coating: about 5 mg desloratadine
• degradation limits as above

B. Example matrix core composition ranges (claim 13)

Claim 13 provides a detailed ingredient mg/core range set:

• Pseudoephedrine sulfate: 120–360 mg
• Hydroxypropyl methylcellulose (HPMC): 2208 mg core? (as written)
• Ethylcellulose: 40–120 mg
• Dibasic calcium phosphate dihydrate: 56–162 mg
• Povidone: 20–60 mg
• Silicon dioxide: 6–12 mg
• Magnesium stearate: 2–6 mg

This is not a full list of every possible formulation ingredient but it does show the patent’s intended coating/matrix design space.

C. Coating polymer and excipient constraints

Key coating classes and examples:

• First coating and/or second coating includes:

  • water-swellable film-forming neutral or cationic copolymeric ester
  • film modifier
  • lubricant
  • optionally anti-foaming agent

• Claim 14 and 15 specify:

  • neutral copolymer of ethyl acrylate and methyl acrylate
  • lubricant selected from talc, silicon, PEG 200–8000
  • PEG selected from PEG 200–8000
  • optional mixture of homologous liquid methyl siloxane polymers and silica gel

• Claim 16 specifies third coating uses:

  • neutral copolymer of ethyl acrylate and methyl acrylate
  • lubricant: talc, silicon dioxide, magnesium stearate
  • water-soluble film-modifier: low viscosity HPMC, HEMC, sodium CMC, or PEG 200–8000
  • dye
  • optional methyl siloxane + silica mixture

D. Solubility/dissolution-directed coating behavior

The use of water-swellable polymers plus water-soluble modifiers suggests the patent claims a specific ER mechanism:

• initial ER release modulated by swellable polymer film and modifiers
• desloratadine positioned in a second coating to drive its release earlier than pseudoephedrine
• optional third film provides physical protection and color while maintaining ER release behavior

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How does the claim scope handle metabolites (3-hydroxydesloratadine)?

Three metabolite-linked limitations appear:

• Claim 2: desloratadine metabolite Cmax window at 5.50–6.25 hours with Cmax about 0.75–1.15 ng/mL.
• Claim 20: steady-state 3-hydroxydesloratadine Cmax and AUC(0–24).
• Claims 27–28: steady-state Cmin/Cmax windows for 3-hydroxy-desloratadine.

This is a strong narrowing lever. If an accused product produces similar parent-desloratadine Cmax but metabolite exposure shifts (bio-transformation kinetics, timing, or clearance differences due to formulation or dosing), it can fall outside these metabolite-specific dependent claims.

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When does US 6,979,463 lose exclusivity, and how do patent term and FDA-related exclusivity interact?

No answer can be produced from the claim text alone. Exclusivity and expiration depend on:

• filing date and patent term adjustments (PTA)
• any terminal disclaimers
• whether patent is listed in FDA Orange Book for specific NDA/ANDA products
• regulatory exclusivity periods for that drug product

Because this analysis requires those concrete dates and Orange Book listings and they are not present in the provided content, no complete and accurate exclusivity timeline can be issued here.

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What patents are likely in the same landscape as US 6,979,463 (and how do you map them)?

No complete and accurate landscape can be produced from the claim text alone. A defensible “patent landscape” requires a search for:

• continuations/divisionals of the same family
• related formulation, coating, and PK patents for the same pseudoephedrine/desloratadine ER combination
• method-of-use patents tied to allergic rhinitis/urticaria indications
• any later generic or follow-on patenting on competing ER co-formulations

Without the patent’s bibliographic identifiers (assignee, application number, priority date) and without citation of other specific patents, any list would be speculative.

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What is the infringement risk for generic or follow-on ER co-formulations?

1) The highest-risk route for a challenger is “same design, same PK”

If a follow-on applicant develops a product that reproduces the same:

• pseudoephedrine ER profile around 7.6–8.4 hours Cmax at 345–365 ng/mL, and
• desloratadine ER profile around 4.0–4.5 hours Cmax at 2.10–2.45 ng/mL, then the product is at high risk for mapping to claim 1.

2) The main “design-around” levers are not content; they are exposure and coating architecture

The claim’s dependence on PK windows and explicit coating components means design-around strategies tend to focus on:

• shifting pseudoephedrine Cmax timing or geometric Cmax out of the claimed windows
• shifting desloratadine Cmax timing or geometric Cmax out of the claimed windows
• changing coating polymers/modifiers/lubricants such that release mechanism changes
• altering degradation profile to exceed the dependent claim stability limits
• altering dissolution performance to miss the dissolution endpoints

3) Method-of-use claims are tethered to claim 1 composition

Claims 29–32 require administering “an effective amount of the extended release solid composition of claim 1.” That tether makes method-of-use infringement follow product infringement.

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What regulatory and litigation posture is implied by these claim types (and how should it affect strategy)?

FDA regulatory posture implied by the claim style

The patent is an ER fixed-dose combination product (pseudoephedrine + desloratadine) with PK and dissolution tests. That usually correlates with Orange Book listing as a drug product patent. But Orange Book status requires listing data, which is not included in the prompt.

Litigation posture suggested by “PK-locked” dependent claims

PK-locked claims tend to:

• drive litigation into bioequivalence study design, statistical treatment of geometric means, and bridging between test conditions and the patent’s “about” ranges
• make “expert results” and “study comparability” central to claim mapping

But the actual litigation history for this specific patent cannot be asserted without case citations.

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Key Takeaways

• US 6,979,463 is tightly scoped around an ER solid oral co-composition of pseudoephedrine and desloratadine with a defined layered coating architecture.
• The independent and dependent claims are anchored to specific pharmacokinetic windows for pseudoephedrine and desloratadine (and metabolite 3-hydroxydesloratadine), including single-dose Cmax and steady-state Cmax/Cmin/AUC.
• Dependent claims also impose formulation performance constraints (dissolution) and stability/degradation limits (desloratadine degradation products including N-methyldesloratadine and N-formyldesloratadine; pseudoephedrine degradation products).
• The most relevant design-around levers for competitors are not merely swapping excipients, but producing a product whose in vivo exposure profile and release performance do not land within the claimed windows and endpoints.

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FAQs

1. What does it mean for a claim to require a geometric Cmax at a specific time window in an ER formulation patent?
2. Do metabolite exposure limits (3-hydroxydesloratadine) create additional infringement risk beyond parent-desloratadine PK?
3. How do dissolution test endpoints in dependent claims affect freedom-to-operate for ER co-formulations?
4. Which claim elements typically become the biggest evidence burden in enforcement of PK-locked ER composition patents?
5. How can a competitor strategically shift ER release to avoid falling within narrow pseudoephedrine and desloratadine exposure windows?

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References

1. (No external sources were provided in the prompt, and no bibliographic details or Orange Book/litigation data were included. Therefore no citations can be generated.)

Drugs Protected by US Patent 6,979,463

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 6,979,463

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	027033
Austria	463240
Australia	2005203771
Australia	2009200460