Details for Patent: 6,015,577

Summary for Patent: 6,015,577

Title:	Pharmaceutical compositions containing dipyridamole or mopidamol and acetylsalicylic acid or the physiologically acceptable salts thereof, processes for preparing them and their use in treating clot formation
Abstract:	The specification describes a pharmaceutical combination consisting of dipyridamole or mopidamol and acetylsalicylic acid or the physiologically acceptable salts thereof, processes for preparing this pharmaceutical combination and the use thereof for the controlled prevention of clot formation.
Inventor(s):	Wolfgang Eisert, Peter Gruber
Assignee:	Boehringer Ingelheim Pharma GmbH and Co KG
Application Number:	US08/421,351
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,015,577
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Patent 6,015,577 (Dipyridamole + Acetylsalicylic Acid Combination): Claims Scope, Enforceable Boundaries, and US Landscape

United States Patent 6,015,577 protects an oral, capsule-contained combination of a “first component” (dipyridamole or a pharmaceutically acceptable salt) and a “second component” (acetylsalicylic acid or a pharmaceutically acceptable salt), with a tight numeric relationship between the actives and a defined acid-excipient and enteric-coating system for the dipyridamole-containing sub-formulation, while the acetylsalicylic acid is formulated as a tablet with a sucrose coating. The patent also claims multiple medical-use methods tied to clot prevention and specific vascular outcomes.

This analysis breaks the claims into (i) composition boundaries, (ii) coating and excipient limitations that narrow scope in practice, (iii) dosage and ratio embodiments, and (iv) method-of-use claims that can extend protection even where formulation details differ only partially.

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What is the core claimed invention?

The core is a two-active oral capsule product plus corresponding therapeutic method claims.

Claim nucleus (repeated across independent claims)

• Actives
  • First component: dipyridamole (or acceptable salt)
  • Second component: acetylsalicylic acid (aspirin) (or acceptable salt)
• Weight ratio requirement
  • 8:1 to 100:1 (dipyridamole : acetylsalicylic acid)
• Single oral capsule presentation
  • All components are contained together within a capsule
• Formulation separation
  • Dipyridamole is present as granules (Claim 1) or pellets (Claim 2) with an acid excipient and a defined enteric-coating system
  • Acetylsalicylic acid is present as a tablet
• Acid excipient + stoichiometric constraint
  • Acid excipient “formulated together with” dipyridamole in granules/pellets
  • Acid excipient ratio: at least one equivalent of said acid excipient to 1 mol of first component
• Enteric/lacquer composition constraint
  • Coating made of two classes of “lacqueurs”
  • Class A: insoluble in acid but soluble in intestinal juices
  • Class B: insoluble in both gastric and intestinal juices
  • Class A fraction: 50% to 100%
  • Class B fraction: 50% to 0%
  • In dependent claims, Class A and Class B are defined by polymer families (methacrylate/cellulose phthalates vs acrylate/methacrylate with limited ethylcellulose content).

Therapeutic core (method claims)

• Methods for inhibiting:
  • formation of venous and arterial blood clots (Claim 16)
  • temporary ischemic episodes (Claim 17)
  • strokes caused by blood clots (Claim 18)
  • cardiac infarctions (Claim 19)
• One additional patient-risk modifier:
  • patient suffers from arteriosclerosis (Claim 20)

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How broad are the composition claims in terms of actives and ratio?

Actives (broad)

The independent composition claims cover:

• Dipyridamole and acceptable salts
• Acetylsalicylic acid and acceptable salts

This is broad on drug substance identity: formulations using salts remain within literal scope if the salts are “pharmaceutically acceptable” as construed in US practice.

Ratio (moderately tight but still wide)

The claimed dipyridamole:aspirin weight ratio spans:

• 8:1 to 100:1 (inclusive per typical claim construction unless otherwise specified)

Dependent embodiments further lock numeric examples:

• Claim 14 sets final dosage comprising 200 mg dipyridamole and 25 mg acetylsalicylic acid and weight ratio 8:1.

Practical implication: Even if a competitor selects an 8:1 ratio, the product must still match the formulation and coating limitations to avoid infringement of the key composition claims. Conversely, even at ratios within 8:1 to 100:1, avoiding the coating and acid-excipient system is a primary design-out lever.

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What does the formulation architecture require, and where are infringement “pressure points”?

The independent claims (1 and 2) are not just about the combination drugs. They require a specific multi-unit design and internal formulation rules.

1) Dipyridamole form: granules vs pellets

• Claim 1: dipyridamole in granules
• Claim 2: dipyridamole in pellets

If a product uses neither granules nor pellets, that is not an automatic “safe harbor” because doctrine of equivalents could be argued depending on prosecution history; but for clean non-infringement at claim construction stage, the structural limitation is a real boundary.

2) Acid excipient in defined stoichiometry

Independent claims require:

• acid excipient “formulated together with said first component”
• acid excipient in a ratio of at least one equivalent acid excipient per 1 mol dipyridamole

Dependent claims restrict acid excipient options:

• Claim 3/4: fumaric, tartaric, citric, succinic, malic
• Claim 5/6: fumaric and tartaric only

Pressure point: If a competitor uses a different acid excipient or uses less than stoichiometric equivalents, they can avoid literal satisfaction of the “at least one equivalent” requirement, depending on how “equivalent” is calculated for the acid and salt form used.

3) Enteric coating system: two “lacqueur” classes with fraction boundaries

Independent claims require the coating made up of two lacqueur categories with explicit ranges:

• 50 to 100% lacqueurs insoluble in acid but soluble in intestinal juice
• 50 to 0% lacqueurs insoluble in both gastric and intestinal juices

Dependent claims narrow to polymer sets.

4) Defined polymer families (dependent claims 7 and 8)

Class A (acid-insoluble, intestinal-soluble) examples

• methacrylic acid/methacrylic acid ester copolymers
• hydroxypropylmethylcellulose phthalate (HPMCP)
• cellulose acetate phthalate (CAP)
• ethylcellulose phthalate
• hydroxypropylmethylcellulose succinate (HPMCS)
• cellulose acetate succinate (CAS)
• hydroxypropylmethylcellulose hexahydrophthalate
• cellulose acetate hexahydrophthalate
• hydroxypropylmethylcellulose trimellitate

Class B (insoluble in both gastric and intestinal juices) examples

• acrylate, methacrylate, mixtures with up to 14% by weight ethylcellulose

Pressure point: Many enteric polymers exist. The claims, as drafted, map to specific “lacqueur” families and a defined ethylcellulose ceiling for the Class B component. A competitor can design around by selecting polymer families outside these groups or by formulating outside the fraction rules.

5) Acetylsalicylic acid sub-formulation: tablet with sucrose coating

Dependent claims add:

• tablet coating comprises sucrose (Claims 9 and 10)

Claim 1/2 require aspirin as a tablet, but do not state sucrose in the independent claim text you provided. Dependent claims make sucrose a specific limitation.

6) Tablet and capsule “together within a capsule”

Independent claims require:

• both the dipyridamole-containing granules/pellets and the acetylsalicylic acid tablet are contained together within a capsule.

Pressure point: A competitor that uses a dual capsule system (separate capsule units) could avoid the “within a capsule” literal requirement for these particular independent claims, though method claims can still be asserted under combination administration theories.

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What are the key dependent-claim constraints that materially narrow the scope?

Acid excipient selection (Claims 3-6)

These narrow the identity of acid excipients:

• Expanded list: fumaric, tartaric, citric, succinic, malic (Claims 3-4)
• Tight list: fumaric and tartaric only (Claims 5-6)

Enteric coating polymer selection and ratios (Claims 7-8, 9-10)

• The Class A polymers are limited to a listed group.
• The Class B polymers are limited to acrylate/methacrylate with up to 14% ethylcellulose.
• Additional dependent layering example:
  • Claim 9/10: dipyridamole granule/pellet coating includes methacrylic acid/methacrylic ester copolymer and HPMCP in weight ratio 85:15 to 50:50
  • aspirin tablet coating comprises sucrose

Dosage amounts (Claims 11-12, 14, 15)

• Claim 11/12: dipyridamole 75–400 mg, aspirin 5–80 mg
• Claim 14: specifically 200 mg dipyridamole + 25 mg aspirin at 8:1
• Claim 15: an explicit structural embodiment:
  • dipyridamole pellets:
  • core consisting of pharmaceutically acceptable acid excipient
  • first coating surrounding core comprising dipyridamole and polyvinylpyrrolidone
  • lacquer top coating comprising methacrylic acid/methylmethacrylate copolymer and HPMCP
  • aspirin tablet:
  • core acetylsalicylic acid + sucrose coating
  • capsule contains both

Pressure point: Claims 11/12 and 14/15 are dosage-specific. If a product uses different strengths outside the ranges, it may avoid dependent claim infringement even if independent claims still read.

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How do the method claims expand the enforceable surface area?

Method claims can bite even if a competitor changes the dosage form architecture, depending on what the claim construction and proof burdens require.

Method claim 16: clot inhibition via ratio-defined administration

Claim 16 requires:

• administering to a patient:
  • first drug: dipyridamole (or salt)
  • second drug: acetylsalicylic acid (or salt)
• weight ratio in administration: 8:1 to 100:1

This is the broadest method-of-use boundary in your set. It does not expressly require capsule architecture, enteric polymers, or the acid excipient system.

Downstream method claims 17-20: specific outcomes and patient condition

• Claim 17: temporary ischemic episodes
• Claim 18: strokes caused by blood clot
• Claim 19: cardiac infarctions
• Claim 20: arteriosclerosis patient

Enforcement posture in the US: Method claims often face higher proof hurdles (clinical outcome, patient selection, and administration ratio), but if a prescribed regimen matches the claimed ratio and indications, these claims can become leverage against branded or generic products using the claimed dosing relationship.

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What does this imply for US patent landscape and competitive freedom-to-operate (high-level mapping)?

Given only the claim text you provided, the US landscape analysis can be done at the level of “what would need to be designed around” and “what other patent families likely exist,” but a complete, citation-backed landscape cannot be generated without the bibliographic data (filing dates, assignee, prosecution history, and citation list) for US 6,015,577 and without access to a patent database. Under the constraint that the response must be complete and accurate, the landscape below is limited to claim-driven design and enforcement mapping rather than an exhaustive family tree.

Likely design-around routes that align with claim boundaries

1. Break the capsule-contained combination structure
   • Use separate dosage units not “together within a capsule” (direct challenge to composition claims 1/2).
2. Break the dipyridamole sub-formulation constraints
   • Use a different acid-excipient system that does not meet “at least one equivalent per 1 mol” constraint.
   • Use enteric coating materials or lacquers outside the listed “Class A/Class B” polymer families or fraction ranges.
3. Break the aspirin tablet coating dependency
   • Avoid sucrose coating if targeting to avoid dependent claims 9/10/15.
4. Break the administered weight ratio
   • Use a regimen outside 8:1 to 100:1 (cuts method claim 16).
5. Break the claimed therapeutic pathway
   • If marketing/labeling focuses on non-claimed indications or patient populations, method enforcement risk changes, though this depends on US litigation strategy and evidentiary record.

Likely infringement patterns

• A product that matches the full capsule architecture, the enteric coating composition, and the acid-excipient stoichiometry will align tightly with Claims 1 and 2 and their narrowed dependents.
• Even if a product changes the formulation slightly, Claim 16 can remain a risk if the dosing regimen uses the same dipyridamole-to-aspirin ratio and targets the claimed outcomes.

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Claim-by-claim scope summary (what each claim actually covers)

Claim	Category	What it requires (key limitations)	Scope impact
1	Composition	Capsule contains dipyridamole granules with acid excipient (>=1 equivalent) and enteric “lacqueur” split; aspirin as tablet; dipyridamole:aspirin 8:1–100:1	High constraint on formulation and coating; broad on acid excipient identity unless dependents used
2	Composition	Same as claim 1 but dipyridamole in pellets (not granules)	Limits to pellet architecture
3	Composition dependent	Acid excipient limited to fumaric/tartaric/citric/succinic/malic	Narrows acid identity
4	Composition dependent	Same narrowing for pellet version	Narrows acid identity
5	Composition dependent	Acid excipient limited to fumaric and tartaric	Strong narrowing
6	Composition dependent	Same narrowing for pellets	Strong narrowing
7	Composition dependent	Lacqueur Class A and Class B polymer families and ethylcellulose ceiling	Narrowest enteric-polymer mapping
8	Composition dependent	Same for pellets	Same narrowing
9	Composition dependent	Granule coating polymer ratio (85:15 to 50:50 of methacrylic acid/methacrylic ester copolymer:HPMCP) and aspirin tablet coating sucrose	Locks coating stack details
10	Composition dependent	Same for pellets and sucrose aspirin coating	Locks coating details
11	Composition dependent	Dose ranges: dipyridamole 75–400 mg, aspirin 5–80 mg	Strength-specific boundary
12	Composition dependent	Same ranges for pellet version	Strength-specific boundary
13	Composition	Simplified composition: actives + ratio only (no explicit formulation/coating requirements in provided text)	Appears broader if fully independent in the original patent text; based only on provided excerpt
14	Composition	Example dosage: 200 mg dipyridamole + 25 mg aspirin, ratio 8:1	Narrow numeric embodiment
15	Composition	Detailed pellet structure (PVP-containing first coating + methacrylic/HPMCP lacquer) and aspirin sucrose-coated tablet in capsule	Very narrow structural example
16	Method	Administer dipyridamole + aspirin at 8:1–100:1 ratio to inhibit venous and arterial clot formation	Broad method risk tied to dosing ratio
17	Method	Temporary ischemic episodes via claim 16	Outcome-specific narrowing
18	Method	Clot-caused strokes via claim 16	Outcome-specific narrowing
19	Method	Cardiac infarctions via claim 16	Outcome-specific narrowing
20	Method	Arteriosclerosis patient via claim 16	Patient-selection narrowing

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What is the most actionable infringement “decision tree”?

1. Does the product administer dipyridamole + acetylsalicylic acid at 8:1 to 100:1?
   • Yes: method claim 16 exposure increases for claimed outcomes.
2. Is the product a capsule containing both components together in the same capsule?
   • Yes: composition claims 1/2 become more relevant.
3. Does the dipyridamole use acid-excipient granules/pellets with >=1 equivalent acid per 1 mol dipyridamole?
   • Yes: enteric-acid system likely satisfies core formulation.
4. Does the dipyridamole enteric coating match the “lacqueur” class split and polymer families?
   • Yes: claims 7/8 style restrictions are more likely to be met.
5. Does the aspirin tablet have a sucrose coating?
   • Yes: claims 9/10/15 risk rises.

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Key Takeaways

• US 6,015,577 protects a dipyridamole plus acetylsalicylic acid oral capsule with a required 8:1 to 100:1 weight ratio and a dipyridamole sub-formulation built on acid excipient stoichiometry (>=1 equivalent per 1 mol dipyridamole) plus a defined enteric lacquer system.
• Dependent claims narrow the scope to specific acid excipients, enteric polymer families, and explicit sucrose-coated aspirin tablets and polymer ratio ranges.
• Method claims (16-20) extend enforceability via administration of both drugs at 8:1 to 100:1 to inhibit clot formation and specific vascular events, without requiring the same formulation architecture.
• The most direct design-arounds that map cleanly to claim language are to (i) break the ratio, (ii) break capsule togetherness, (iii) break the acid-excipient equivalent requirement, and/or (iv) break the enteric lacquer polymer-class/fraction mapping.

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FAQs

1) If a product uses the same 8:1 to 100:1 dipyridamole-to-aspirin ratio, does it automatically infringe?

No. Composition claims also require specific formulation and coating architecture (granules vs pellets, acid-excipient equivalents, and enteric lacquer systems inside the capsule). Method claim 16 risk is the one that primarily follows the ratio.

2) Are dipyridamole and aspirin salt forms included?

Yes. Claims specify dipyridamole and acetylsalicylic acid with “pharmaceutically acceptable salts,” which keeps salts within literal coverage if construed to be acceptable.

3) Which formulation element is usually the hardest for a competitor to change while staying in the same product concept?

The dipyridamole enteric coating architecture and the acid-excipient stoichiometric constraint, because the claim language ties them to explicit equivalents and a defined lacquer class split with polymer-family examples.

4) Does sucrose matter?

Sucrose is a dependent limitation for aspirin tablet coating (Claims 9, 10, and the explicit structure in Claim 15). Avoiding sucrose can help avoid those dependent claim targets, though it does not eliminate exposure to independent composition claim elements that do not state sucrose.

5) Can this patent be asserted against different dosage unit formats?

Composition claims as written require “all components being contained together within a capsule.” If a product uses separate units instead of a single capsule containing both, composition claim literal coverage is weaker. Method claims can still apply if the dosing regimen matches the claimed ratio and outcomes.

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References

[1] United States Patent 6,015,577 (claim text provided by user).

Drugs Protected by US Patent 6,015,577

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: 6,015,577

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	36 27 423	Aug 13, 1986

International Family Members for US Patent 6,015,577

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0257344		SPC/GB98/043	United Kingdom
European Patent Office	0257344		C990001	Netherlands
European Patent Office	0257344		20/1999	Austria
Austria	59961
Australia	603146
Australia	7679587
Brazil	1100593