United States Patent 4,772,475 scope and claims: controlled-release granulation using crystalline cellulose plus acrylic polymer or methacrylic acid-ethyl acrylate copolymers
Executive summary: U.S. Patent 4,772,475 is directed to a controlled-release “granulation product” unit dose (single or multiple unit) that is built around a high fraction of crystalline cellulose (at least 50% by weight) plus release-controlling acrylic-type polymers (acrylic acid polymers, acrylic acid copolymers, or mixtures with cellulose derivatives). Claim coverage narrows further to specific polymer exemplars (methacrylic acid-ethyl acrylate copolymer and ethyl cellulose; optionally water) and a specific active ingredient (YM-12617, 5-{2-[2-(o-ethoxypheoxy)ethylamino]propyl}-2-methoxybenzenesulfonamide hydrochloride). A final dependent claim constrains particle/unit diameter (0.1 to 1.5 mm). Overall, the estate’s enforceable core is the combination of: (i) crystalline cellulose at ≥50% w/w in the granulation, (ii) acrylic/methacrylic release-control polymers (optionally with ethyl cellulose), and (iii) GI release behavior (non-disintegrating, gradual release).
What is the scope of U.S. Patent 4,772,475 controlled-release granulation and how broad is claim coverage?
Core inventive concept (from the claim set you provided):
A controlled-release pharmaceutical oral formulation where an individual unit is a granulation product prepared by granulating:
- a mixture of physiologically active substances and crystalline cellulose, with
- a release controlling agent selected from:
- acrylic acid polymers
- acrylic acid copolymers
- mixtures thereof with cellulose derivatives,
- such that:
- ≥50% by weight crystalline cellulose (based on unit weight), and
- the granulation product does not substantially disintegrate and gradually releases the active substance in the gastrointestinal tract (GI).
Claim 1’s breadth is shaped by three major “pillars”:
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Structural composition constraint (high crystalline cellulose):
- The unit must contain at least 50% crystalline cellulose by weight.
- This is a strong narrowing element; many controlled-release tablets and pellets use microcrystalline cellulose, lactose, starch, or binders at far lower fractions than 50% crystalline cellulose.
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Release-control agent constraint (acrylic-type polymers and certain cellulose derivatives):
- Eligible release controlling agents are limited to acrylic acid polymers, acrylic acid copolymers, and mixtures thereof with cellulose derivatives.
- This is narrower than “any polymer controlling release.” It is closer to an HPMC/Eudragit-like functional class, but the claim language is tethered to acrylic acid polymer/copolymer chemistry.
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Functional GI behavior constraint:
- The granulation product must not substantially disintegrate and must gradually release the active in the GI tract.
- This is a process/functional limitation that can be used to exclude formulations that disintegrate (even if composition resembles the claim).
How “single unit or multiple unit” affects scope
Claim 1 covers:
- a single unit formulation, or
- a multiple unit formulation (for example, many granules/pellets in a capsule).
This expands usage formats but not composition: the granulation product within each individual unit still needs ≥50% crystalline cellulose and the defined polymer system.
Which polymer systems are expressly covered by the claims (acrylic acid polymers vs methacrylic acid-ethyl acrylate copolymer vs ethyl cellulose)?
Claim 1 polymer families:
- Acrylic acid polymers
- Acrylic acid copolymers
- Mixtures thereof with cellulose derivatives
Claim 2 narrows to specific exemplars and co-polymers:
- methacrylic acid-ethyl acrylate copolymer, and
- mixtures of that copolymer and ethyl cellulose.
Claim 3 adds moisture content conceptually:
- The release controlling agent “further contains water.”
Practical implication for design-around and freedom-to-operate
- If a competitor uses a non-acrylic polymer (for example, polyvinyl alcohol, povidone-based matrices, polyethylene glycol systems, or cellulose ethers not used as “mixtures thereof with cellulose derivatives” in the release controlling agent) the formulation may fall outside the polymer selection language.
- If a competitor uses acrylic polymers but not in a granulation with ≥50% crystalline cellulose, they may avoid Claim 1.
- If a competitor uses methacrylic acid-ethyl acrylate plus ethyl cellulose but uses <50% crystalline cellulose, Claim 1 and Claim 2 dependent structure likely fail.
What does “crystalline cellulose at least 50% by weight” mean for claim construction and infringement risk?
Claim 1 expressly requires:
- At least 50% by weight crystalline cellulose based on the weight of the units.
This is a high-content excipient feature. For typical oral controlled-release pellets/tablets, crystalline cellulose can be present but often not at 50% w/w. That makes the claim relatively targeted to a specific excipient-heavy architecture.
Key scope questions resolved by the claim text
- The crystalline cellulose is not merely an excipient; it is a primary component.
- The limitation ties to the “individual unit,” meaning the granulation product material itself (the unit contents), not a surrounding coating layer.
What GI release performance is required and how does that limit the claim?
Claim 1 requires that:
- the granulation product does not substantially disintegrate, and
- it gradually releases the physiologically active substance in the GI tract.
Infringement posture implied by functional language
The functional GI behavior can matter in disputes because it allows argument both ways:
- Patent owner: the accused product’s release profile in GI conditions is consistent with “gradual release” and “does not substantially disintegrate.”
- Accused infringer: the formulation disintegrates and releases rapidly or lacks the claimed “does not substantially disintegrate” behavior.
Because your excerpt does not provide test methods, there is no stated quantitative disintegration metric in the claim text you provided. Still, the language gives the patentee room to argue performance-based conformity.
What active ingredient does U.S. 4,772,475 cover (YM-12617) and does it restrict the claim set?
Claim 4 restricts:
- physiologically active substance = 5-{2-[2-(o-ethoxypheoxy)ethylamino]propyl}-2-methoxybenzenesulfonamide hydrochloride (YM-12617).
Effect on scope:
- Claim 4 is dependent on Claim 1 through Claim 3. The broader formulation architecture in Claim 1 remains applicable to other actives only if those actives fall under “physiologically active substances” generally.
- However, Claim 4 is a specific composition claim tied to YM-12617.
Commercial significance:
- If YM-12617 corresponds to a marketed drug candidate, then Claim 4 becomes a high-value hook.
- If YM-12617 is only a development compound and is not the same as a later marketed active, then Claim 4 may be less commercially relevant while Claim 1-3 still matter for any controlled-release versions using the same excipient/polymer architecture.
How specific is particle or unit size coverage (0.1 to 1.5 mm) in Claim 5?
Claim 5 requires:
- individual unit diameter between 0.1 to 1.5 mm.
Scope impact:
- This is a conventional pellet/powder granule range.
- It narrows coverage for accused products. If a competitor uses larger pellets (for example, >1.5 mm) or smaller granules/powders (<0.1 mm), Claim 5 may not read.
Claim 5 is dependent, so it does not eliminate potential coverage under Claims 1-4 for products outside that size, but it reduces the set of products that can rely on the particle-size hook.
What formulation steps are recited and do they limit manufacturing method coverage?
The claims include a defined preparation step in Claim 1:
- “granulating the resultant mixture”
Claim 1 describes:
- add release controlling agent to a mixture of active + crystalline cellulose,
- in the required proportion,
- then granulate the mixture into the granulation product meeting functional release behavior.
How that matters
- If an accused product is made by a different manufacturing route that still yields the same granulation product characteristics, infringement may still occur depending on how courts treat structural/functional claims tied to the resulting product rather than strict method-only limitations.
- If manufacturing is used as a defense, the “granulating” step provides a basis to argue nonconformance at least for processes that do not involve granulating.
Your excerpt does not include additional process limitations (mixing times, drying conditions, coating steps), so manufacturing carve-outs may be limited by the claim’s focus on the resulting granulation product.
How does the dependent claim chain narrow the patent estate from Claim 1 to Claims 2–5?
Claim dependency map
- Claim 1: General architecture (crystalline cellulose ≥50% + acrylic acid polymers/copolymers + GI gradual release; non-disintegrating)
- Claim 2: Specific polymer selection (methacrylic acid-ethyl acrylate copolymer; optionally with ethyl cellulose)
- Claim 3: Release-controlling agent includes water
- Claim 4: Active specific to YM-12617
- Claim 5: Unit diameter 0.1 to 1.5 mm
Net narrowing
Coverage narrows by:
- polymer exemplar and cellulose co-polymer (Claim 2),
- water content in the release controlling agent (Claim 3),
- specific active ingredient (Claim 4),
- specific unit size range (Claim 5).
Claim 1 is the broadest; Claims 4 and 5 are the most restrictive.
What patent landscape questions can be answered from the claim text alone (expiration, ORANGE BOOK, litigation, Paragraph IV, biosimilar risks)?
None of the landscape items below can be produced accurately from the claim excerpt alone:
- Orange Book status (requires application/NDA/ANDA linkage and Orange Book data)
- Patent expiration dates (requires priority/filing and patent term adjustments)
- Paragraph IV certifications (requires ANDA case information)
- Litigation posture and settlements (requires PACER/docket and docketed litigations)
- Biosimilar risk (only relevant to biologics; this appears to be a small-molecule controlled-release claim but linkage is required)
Per operating constraints, no incomplete landscape elements are provided.
Key claim-by-claim scope table
| Claim |
Required elements (as provided) |
Main scope impact |
| 1 |
Controlled-release individual unit or multiple unit formulation; unit consists essentially of granulation product; granulation product made by adding release controlling agent selected from acrylic acid polymers / acrylic acid copolymers / mixtures with cellulose derivatives to mixture of physiologically active substances + crystalline cellulose; crystalline cellulose ≥50% w/w; granulation product does not substantially disintegrate and gradually releases active in GI |
Defines the enforceable core: excipient-heavy crystalline cellulose + acrylic polymer release control + GI functional release |
| 2 |
Release controlling agent is methacrylic acid-ethyl acrylate copolymer or mixtures of copolymer and ethyl cellulose |
Narrows polymer family to specific methacrylic copolymer and ethyl cellulose combinations |
| 3 |
Release controlling agent further contains water |
Narrows release-control agent composition to include water presence/role |
| 4 |
Physiologically active substance is YM-12617 (5-{2-[2-(o-ethoxypheoxy)ethylamino]propyl}-2-methoxybenzenesulfonamide hydrochloride) |
Narrows active ingredient to a specific molecule |
| 5 |
Individual unit diameter is 0.1 to 1.5 mm |
Narrows physical size of granulation product/unit |
How strong is the patent’s claim coverage for “design-around” scenarios?
Most straightforward ways to avoid Claim 1 (from a text-reading perspective):
- Use <50% by weight crystalline cellulose in the granulation unit.
- Use a release-control agent outside the defined acrylic acid polymer/copolymer families and cellulose-derivative mixtures.
- Engineer a formulation that substantially disintegrates rather than maintaining integrity and gradually releasing in GI.
Ways that still risk Claim 1 exposure:
- Matching the high crystalline cellulose fraction and using acrylic acid polymer/copolymer release agents, even with different active ingredients (since Claim 1 covers “physiologically active substances” broadly).
Claim 2/3/4/5 add narrower “hooks” that can be avoided by changing polymer exemplar, excluding water from release controlling agent, changing the active from YM-12617, or changing granule/unit diameter.
Key Takeaways
- Claim 1 is the core: a granulation product oral controlled-release system with ≥50% crystalline cellulose plus acrylic acid polymer/copolymer (optionally with cellulose derivatives), showing GI gradual release without substantial disintegration.
- Claims 2–3 narrow to methacrylic acid-ethyl acrylate copolymer (optionally with ethyl cellulose) and add that the release-controlling agent includes water.
- Claim 4 narrows the active to YM-12617.
- Claim 5 narrows granulation/unit diameter to 0.1–1.5 mm.
- The excerpt supports high-confidence scope boundaries, but no reliable dataset for Orange Book, litigation, expiry dates, or Paragraph IV/biosimilar status.
FAQs
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If a formulation uses crystalline cellulose but only 30% w/w, does it still fall under U.S. 4,772,475 Claim 1?
The claim text requires ≥50% by weight crystalline cellulose in the unit.
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Do the claims require methacrylic acid-ethyl acrylate copolymer?
No. Claim 1 covers acrylic acid polymers/copolymers broadly; methacrylic acid-ethyl acrylate is only expressly required in Claim 2.
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Is YM-12617 required for infringement of the broadest claim?
No. YM-12617 is only specified in the dependent Claim 4; Claim 1 covers “physiologically active substances” generally.
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What happens if a product’s granules are smaller than 0.1 mm?
Claim 5 would not read, since it requires diameter 0.1–1.5 mm.
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Can a formulation be outside the claim if it disintegrates in the GI tract?
The claim requires the granulation product to not substantially disintegrate while releasing gradually in the GI tract, so disintegration behavior is a limiting element.
References
- United States Patent 4,772,475, claims 1–5 (text provided in prompt).
