United States Patent 6,641,841 Scope, Claim-by-Claim Breakdown, and US Patent Landscape for Tablet Manufacturing with N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine and Superdisintegrants

Executive summary: US Patent 6,641,841 claims a US tablet manufacturing process for drug substance N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (the active) using a defined set of cellulose-based or crosslinked disintegrants and a granulation–drying–tableting workflow, with optional coating and a downstream method-of-use to inhibit blood sugar rise. The patent’s practical enforcement boundary is narrow: it is process-and-product tied to (i) the specific active identity, (ii) a short, enumerated disintegrant genus, (iii) wet granulation with water (optionally with lower alcohol), and (iv) (for claims 2–4) a spray coating limitation that narrows to hydroxypropylmethyl cellulose in the coating liquid. The most material “design-around” routes are to change any single required element: disintegrant identity, granulation solvent system, granulation step, dosage form structure (tablet vs other solid oral form), or active salt/derivative identity if it avoids the literal “N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine” requirement.

What does US Patent 6,641,841 claim, and what parts are legally limiting?

Short answer: The patent is anchored by six independent or semidependent claim themes: (1) a specific wet-granulation tablet process with enumerated disintegrants, (2) optional coating, (3) optional spray coating, (4) spray coating where the coating liquid contains hydroxypropylmethyl cellulose, (5) the product-by-process tablet made by that process, and (6) a method-of-use for glycemic control using the claimed tablet.

Claim architecture and limiting elements

Claim 1 (process core) is the anchor. It requires, in one continuous workflow:

Tablet process steps
- mixing the active N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine with a disintegrant selected from:
  - low substituted hydroxypropylcellulose (low substituted HPC),
  - sodium carboxymethyl cellulose (NaCMC),
  - calcium carboxymethyl cellulose (CaCMC),
  - croscaramellose sodium (crosslinked Na salt of carboxymethylcellulose).
- granulating the mixture with water, optionally with a lower alcohol,
- drying granules,
- tableting dried granules.
Key constraint: The disintegrant selection is explicitly enumerated. This is often the easiest infringement switch because it is not expressed as a broad “disintegrant comprising any superdisintegrant” type of language.
Key constraint: Solvent system for granulation is water, optionally plus a lower alcohol. Replacing the granulation liquid with a non-water system (or eliminating wet granulation entirely) is a typical design-around.

Claim 2 (coating): adds “coating said tablet to obtain a coated tablet.” It is dependent on Claim 1, so it still requires the Claim 1 process.

Claim 3 (spray coating): narrows Claim 2 by requiring spray coated tablet.

Claim 4 (spray coating composition): narrows Claim 3 further by requiring spray coating with a coating liquid comprising hydroxypropylmethyl cellulose (HPMC).

Claim 5 (product-by-process): claims “a tablet produced by the process of claim 1.” This gives an additional claim vector, but product-by-process claims typically require structural identity analysis in litigation. If the product has distinguishing structural features (e.g., composition, internal porosity, disintegrant distribution), enforcement can still be meaningful.

Claim 6 (method-of-use): administers “the tablet of claim 5” to inhibit the rise of blood sugar. This is dependent on the product-by-process claim, so infringement typically requires proving use of the claimed tablet.

How broad is the disintegrant scope in claim 1, and what’s the practical infringement boundary?

Featured snippet answer: Claim 1 limits disintegrants to four enumerated cellulose/crosslinked cellulose materials: low-substituted hydroxypropylcellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, or croscaramellose sodium.

Disintegrant-by-disintegrant claim implications

Disintegrant in claim 1	Literal inclusion	Likely design-around by substitution
Low substituted hydroxypropylcellulose (HPC, low substituted)	Covered if “low substituted” is met	Use a different grade (higher substitution HPC), or use a different superdisintegrant class (e.g., crospovidone)
Sodium carboxymethyl cellulose (NaCMC)	Covered	Replace with crosslinked povidone or other non-enumerated disintegrant
Calcium carboxymethyl cellulose (CaCMC)	Covered	Replace with another salt form not enumerated or another disintegrant category
Croscaramellose sodium	Covered if it matches the named material	Replace with similar crosslinked cellulose materials not named

What is not in claim 1

The claim language you provided does not include other common tablet disintegrants like crospovidone, sodium starch glycolate, polacrilin potassium, or other polymer-based disintegrants unless they fall under one of the enumerated materials.

Does claim 1 require wet granulation only, or is dry processing protected too?

Short answer: Claim 1 requires granulating said mixture with water (optionally with lower alcohol) and then drying granules and tableting. A dry direct-compression route is outside the literal language.

Design-around pathways implied by the claim steps

Direct compression (no wet granulation) likely avoids Claim 1 literal coverage.
Dry granulation/slugging likely avoids the “granulating … with water” requirement.
Aqueous granulation is core; switching to a non-aqueous granulation liquid would be a key design-around if it avoids “water” as the granulating medium.

How do claims 2–4 narrow scope around coating and spray coating with HPMC?

Featured snippet answer: Claims 2–4 are dependent and narrow: spray coating is required in Claim 3, and the spray coating liquid must comprise hydroxypropylmethyl cellulose in Claim 4.

Practical enforcement leverage

If an accused tablet is coated but not spray coated, it may fall outside Claims 3–4, but could still face Claim 2 exposure if Claim 2 is asserted.
If it is spray coated but uses a coating polymer system not “comprising hydroxypropylmethyl cellulose,” Claim 4 likely fails. Claim 3 might still be targeted depending on the claim set asserted and the prosecution history.

Common litigation question for dependent coating claims

Courts typically parse dependent claims strictly. Claim 4 adds a composition limitation (coating liquid comprising HPMC). If HPMC is present only in trace amounts or is substituted by other cellulosic polymers, the question becomes whether the claim requires more than incidental presence, which depends on specification and claim interpretation.

How does claim 5’s product-by-process format affect validity and infringement?

Short answer: Claim 5 covers “a tablet produced by the process of claim 1,” which ties the product claim to the manufacturing process. In litigation, the court may require showing that the accused tablet is the same product obtainable by the claimed process, often using composition and potentially performance indicators.

What helps enforcement for product-by-process

If the accused tablet uses the same enumerated disintegrant and results in similar tablet microstructure or dissolution profile driven by the process, the “produced by” hook is easier to satisfy.
If the product is manufactured differently but yields similar performance, defenses often argue non-infringement or invalidity.

What helps design-around for product-by-process

Changing just one literal requirement in Claim 1 (disintegrant or granulation liquid) can help argue the accused tablet is not “produced by” the process as claimed.

How strong is the method-of-use claim 6, and what are common infringement proof issues?

Featured snippet answer: Claim 6 covers administering the claimed tablet to inhibit the rise of blood sugar. It is dependent on Claim 5, so infringement requires using the tablet made by the Claim 1 process.

Typical enforcement bottlenecks for method-of-use

Proving that a defendant’s product corresponds to the “tablet of claim 5.”
Establishing the claimed physiological effect (inhibiting rise of blood sugar). In practice, label indication, prescribing behavior, and study data can matter.

What does the claim set suggest about the intended product (and where the patent likely sits in a lifecycle)?

Short answer: The claim set is a classic formulation-manufacturing patent paired with a functional method-of-use. It targets a particular tablet formulation route and then extends protection into use.

Lifecycle implication

Because the patent claims manufacturing steps and a dosage form, it is most relevant during:

launch and early years when original tablets are produced under the patented process, and
generic or follow-on competition when innovators are looking to block “same dosage form, same manufacturing process” entrants.

How many other US patents usually cluster around this kind of formulation process, and what are the likely categories?

Without listing an actual family set from public registries in your prompt, the safest “landscape” framing is categorical: formulation process patents like 6,641,841 typically cluster with adjacent claims across four buckets.

Common adjacent US patent buckets seen in similar formulation portfolios

Other tablet manufacturing processes
- different granulation liquids
- different binder/disintegrant ratios
- alternative drying conditions
Coating process patents
- different coating polymers (HPMC, ethylcellulose, PEG/plasticizer systems)
- different coating weights and spray parameters
Composition patents
- explicit claims to the tablet composition (not just process)
Method-of-use or therapeutic regimen patents
- dosing, frequency, subject populations, and measured glycemic endpoints

For decision-making, the key question is not “how many patents exist,” but whether they share the same litigation-critical limitations:

active identity,
disintegrant enumeration,
wet granulation with water (+ optionally lower alcohol),
spray coating with HPMC.

What are the main design-around levers for US 6,641,841?

Featured snippet answer: The highest-impact design-around moves are (i) swap to a non-enumerated disintegrant, (ii) avoid wet granulation with water, (iii) avoid spray coating, and (iv) use a coating system that does not comprise HPMC.

Claim-specific design-around checklist

To avoid Claim 1

Use a disintegrant not in the four-item list.
Change granulation liquid to non-water (or eliminate wet granulation).
Use direct compression without wet granulation/drying granules.

To avoid Claims 2–4

Avoid coating altogether (hardest for stability).
If coated, avoid spray coating.
If spray coated, use coating liquid not comprising HPMC.

To avoid Claim 6

Ensure the administered product is not “the tablet of claim 5,” which practically means it does not meet Claim 1 process requirements.

How does the patent likely map to FDA Orange Book listing and generic risk?

Short answer: This is a formulation-process and method-of-use patent. Its Orange Book relevance depends on whether it is listed for a specific NDA/ANDA product and tied to a listed drug. Process patents often appear in the Orange Book only if listed by the NDA holder with the relevant NDA product and exclusivity periods.

Generic entry risk framing

A generic that makes tablets using a different disintegrant and different granulation method often lowers literal infringement risk.
A generic using the same enumerated disintegrants and aqueous wet granulation with the optional alcohol step keeps more of the claim 1 footprint.
For coated products, coating method and polymer composition determine exposure to claims 2–4.

What litigation theory is most plausible if 6,641,841 is asserted?

Short answer: The core enforcement theory centers on Claim 1 (process) and Claim 5 (product-by-process) for manufacturing and composition correspondence, with Claim 6 added for method-of-use in prescribing and use contexts.

Likely plaintiffs’ infringement arguments

Prove disintegrant identity and grade (e.g., “low substituted” HPC).
Prove process step sequence: mixing, wet granulation with water ± lower alcohol, drying granules, tableting.
For coated versions, show spray coating and HPMC-containing coating liquid.
For product-by-process, argue that the accused tablet is produced by the claimed process and therefore falls within Claim 5.

Likely defenses

Disintegrant not in the enumerated set.
No wet granulation with water (or different granulating vehicle).
Coating is not spray coated or coating liquid does not comprise HPMC.
For method-of-use, argue product mismatch (Claim 5 not met).

Key Takeaways

US 6,641,841 is narrowly focused on a tablet manufacturing process for N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine using four enumerated disintegrants and wet granulation with water (optionally plus lower alcohol).
Claims 2–4 add coating constraints: spray coating is required and the coating liquid must comprise HPMC in Claim 4.
Claim 5 is a product-by-process hook tied to Claim 1’s process limitations, so design-arounds that break any Claim 1 element can reduce exposure.
Claim 6 depends on administering the claimed tablet to inhibit blood sugar rise, so infringement typically requires proving the accused product matches the claimed tablet.

FAQs

Can a tablet that uses a different disintegrant avoid US 6,641,841 exposure?
Yes, because Claim 1 restricts the disintegrant to a four-item enumerated set.
Does US 6,641,841 cover direct compression tablets?
No, Claim 1 requires wet granulation with water, drying granules, and then tableting.
If a tablet is coated but not spray coated, which claims are still at issue?
Claim 2 may still apply; Claims 3–4 require spray coating, and Claim 4 additionally requires an HPMC-containing spray coating liquid.
What is the critical limitation in claim 4 that enables design-around?
The spray coating liquid must comprise hydroxypropylmethyl cellulose; using a coating system without HPMC can avoid Claim 4.
How does the product-by-process claim 5 typically change generic design and proof?
It pushes analysis to whether the accused tablet is effectively “produced by” the claimed process, which often turns on matching disintegrant identity and wet granulation steps.

References (APA)

United States Patent No. 6,641,841. (n.d.). United States Patent and Trademark Office.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	8-318541	Nov 15, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	322260	⤷ Start Trial
Austria	503472	⤷ Start Trial
Australia	4965497	⤷ Start Trial
Australia	718350	⤷ Start Trial
Canada	2271865	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,641,841

Summary for Patent: 6,641,841