United States Patent 5,260,074: Claims, Technical Scope, and US Landscape

US Patent 5,260,074 (“US5260074”) claims a manufacturing process and an oral dosing method for a combined digestive enzyme and bile salt product formulated as acid-resistant, neutral/basic disintegrating particles. The claims are tightly tied to (1) specific excipient classes and concentration bands, (2) a defined wetting solvent system built around ethanol/propanol/methanol with low water content, and (3) a particle engineering sequence ending in a gastric acid-resistant coating that dissolves under neutral or basic conditions. The patent also carries formulation-identity risk because it claims a process for “preparing” the composition while simultaneously stating a treatment method that reads directly on oral administration of the made product.

What is claimed (and what the claims actually cover)?

Core independent claim structure (Claim 1)

Claim 1 is a multi-step process that starts with dry blending and ends with a neutral/basic dissolving gastric-resistant coating. The claim requires all steps.

A. Dry blending composition (percent-by-weight ranges) The blended dry powder contains:

Enzyme (71 to 90% w/w)
Enzyme selected from pancreatic proteases, lipases, nucleases, and amylases.
Ursodeoxycholic acid salt (1.0 to 61% w/w)
Salt of ursodeoxycholic acid selected from sodium, potassium, ammonium, tromethamine, ethanolamine, diethanolamine, triethanolamine.
Buffering agent system (0.8 to 5.0% w/w buffering agent + 0.8 to 1.5% w/w base amine)
- Buffering agent: anhydrous sodium carbonate, sodium bicarbonate, potassium carbonate, or potassium bicarbonate
- In combination with: tromethamine OR diethanolamine OR triethanolamine (0.8 to 1.5% w/w)
Adhesive polymer (0.3 to 19% w/w)
Hydroxypropyl cellulose, polyvinylpyrrolidone, cellulose acetate, phthalate, methyl cellulose.
Disintegrant (0.9 to 16% w/w)
Starch, modified starches, microcrystalline cellulose, propylene glycol alginate.

This dry blend must fall inside all ranges concurrently to land within Claim 1.

B. Wetting step with specified solvent bands (liquid class constraints) The wetting liquid is selected from three alternative formulations:

Ethanol/propanol/water
- 1 to 25% w/w ethanol
- 75 to 99% w/w 2-propanol
- 0.2 to 2% w/w water
Propanol/water only
- 98 to 99% w/w 2-propanol
- 0.2 to 2% w/w water
Methanol/propanol/water/ethyl acetate
- 1 to 25% w/w methanol
- 0.2 to 2% w/w water
- 75 to 98% w/w 2-propanol
- 1 to 5% w/w ethylacetate

C. Particle formation and size control

Granulating or extruding through a 10 or 18 mesh S/S screen
Converting granules to uniform diameter particle size
Compacting into spherical particles
Drying spherical particles

D. Enteric-style coating with dual-condition dissolution

Coating with gastric acid-resistant polymer that disintegrates under neutral or basic conditions
Dry drying of coated particles

That last feature is critical: it is not just “gastro-resistant”; it is “acid-resistant” with disintegration under neutral/basic conditions, positioning a neutral or intestinal release trigger.

Dependent claims that narrow scope

Key dependent claims tighten product identity and process parameters:

Claim 2: enumerates specific enzymes (Pancreatin, Pancrelipase, trypsin, chymotrypsin, carboxypeptidases, phospholipase A2, α-amylase, papain, bromelain, cellulase, β-galactosidase, etc.). This expands coverage to many commercially known enzyme actives if used inside Claim 1’s structural framework.
Claim 3: composition as microspheres with mesh size about 10 to 80. This likely maps to sieve-based size distribution or particle grading.
Claim 4-6: water content constraint for the wetting liquid:
- Claim 4: 0.2% to 2.0%
- Claim 5: 0.2% to 1.5%
- Claim 6: 0.2% to 1.0%
Claim 7: “seeds” particle size range 20 to 60 mesh (ties to staging in Claim 8).
Claim 8: alternative manufacturing route including “starting seeds” and then tumbling with additional buffered bile salt/enzyme/disintegrant to make 10 to 20 mesh particles, followed by the same gastric acid-resistant coating and final drying. This is a second independent process pathway embedded as a dependent claim.
Claim 9: starting seed bile salt alternatives beyond just salts of ursodeoxycholic acid, including:
- sodium/potassium salts of ursodeoxycholic acid
- ethyl/propyl esters of ursodeoxycholic acid
- sodium/potassium salts of glycyl tauroursodeoxycholate and related N-methyl glycyl/tauroursodeoxycholate.
Claim 10: Oral administration of a therapeutically effective amount of the Claim 1 composition to treat digestive enzyme and bile salt deficiencies.

Where do claims get narrowest (what breaks infringement)?

Hard-to-avoid claim elements

For a process claim, infringement generally requires proof that a defendant performs each required step. In Claim 1, the following elements are the most “hard”:

Exact excipient class + range bundling
Enzyme 71 to 90% w/w and ursodeoxycholic salt 1 to 61% w/w plus buffer system 0.8 to 5.0% + base amine 0.8 to 1.5% must all co-exist in the dry blend.
Wet solvent formulation with defined water content
The wetting liquid must be selected from the three specified solvent families and include the stated water range. If a product uses an aqueous binder, PEG binder, or typical aqueous granulation without the listed ethanol/propanol/methanol system, it is structurally outside the claim’s defined liquid options.
Sieve screen granulation/extrusion step
“10 or 18 mesh” S/S screen is explicitly constrained.
Spherical particle compaction + drying + enteric polymer that disintegrates under neutral/basic conditions
Many enteric coatings fail the “neutral/basic disintegrates” requirement depending on polymer selection, dissolution mechanism, and pH profile.
All steps in order
Process claims often fail if the accused process is step-shifted, continuous instead of batch, or omits a required intermediate like “uniform diameter particle size” or the “compacting into spherical particles” step.

Soft claim elements (easier to align)

The claim is broad in several ways that can make alignment easy if the process uses the same core architecture:

Enzyme universe is wide in Claim 2, covering many digestive enzyme actives.
Adhesive polymer and disintegrant lists are broad.
Particle size outcomes are stated via sieve mesh and in Claim 3/7/8, giving multiple potential internal compliance routes.

What is the likely commercial intent? (technical interpretation tied to claim structure)

The patent’s manufacturing logic is consistent with an oral combination product where:

Enzymes need protection through gastric passage.
Bile salts (ursodeoxycholic acid salts and related derivatives) are buffered and co-formulated with disintegrants.
A gastric acid-resistant polymer coat delays release until the environment becomes neutral or basic.
Solvent-based wetting with low water content reduces enzymatic degradation versus purely aqueous granulation, while enabling granulation/agglomeration.

The claim language supports a strong coupling between process chemistry (solvents, low water) and downstream particle engineering (seeds, mesh sizing, spherical compaction) plus a defined coating release trigger (neutral/basic disintegration).

Claim 10: product-by-process enforcement risk

Claim 10 is a method of treatment requiring oral administration of the Claim 1 composition. That matters for two reasons:

If the underlying composition is made via the Claim 1 process, oral dosing is directly within the claimed treatment method.
If a party markets an equivalent product, the pathway to infringement will likely pivot on proof of how the product was manufactured or the equivalence of the manufacturing steps and final particle characteristics.

Because Claim 1 is process-limited, Claim 10 may be harder to enforce without evidence the accused product was actually produced using the claimed process. Still, in dispute, the focal points will be the solvent wetting system, particle engineering steps, and coating behavior.

How strong are the claims as patent barriers (critical assessment)?

Strengths

Process precision: the solvent system, mesh screen granulation/extrusion, and enteric polymer requirement are specific. This reduces the number of manufacturing “design-arounds” that can simultaneously keep the same functional outcome while removing all literal elements.
Multi-parameter excipient bands: enzyme and bile salt range overlap with many potential formulations but the presence of the combined buffering agent plus specified base amine band is a distinct combination constraint.
Spherical particles and seed/tumbling route (Claim 8): the patent adds an alternate staged manufacturing approach that broadens coverage against process variations within the same manufacturing family.

Weaknesses / litigation friction

Functional coating language: “gastric acid-resistant polymer that disintegrates under neutral or basic conditions” is a functional statement. Many commercial enteric polymers claim similar behavior in practice, and disputes often hinge on coating polymer identity, thickness, and dissolution/disintegration curves rather than process text alone.
Broad excipient lists with wide ranges: lists of adhesive polymers, disintegrants, enzymes, and bile salt seed alternatives create coverage breadth. But that breadth can also be attacked via obviousness based on known enteric enzyme-bile salt formulations and known enteric coating polymers, especially if prior art already teaches solvent-based granulation with low water and enteric coatings.
Process claim proof burden: infringement requires evidence of manufacturing steps. Many disputes in this space are settled or litigated on discovery of process documents, batch records, and formulation master files, with less reliance on end-product tests alone.

US patent landscape: what to watch for around US5260074

Landscape axis 1: oral enzyme and bile acid/bile salt combination products

US5260074 sits at the intersection of:

digestive enzyme replacement products,
bile acid or bile salt therapy for bile acid deficiency states, and
oral protective formulation using enteric or gastric-resistant coatings.

Where the landscape becomes crowded is not in “whether” such products exist, but in how their manufacturing processes are done and how their release is triggered.

Landscape axis 2: bile salts and ursodeoxycholic acid derivatives

Claim 1 centers on ursodeoxycholic acid salts with a separate dependent claim (Claim 9) broadening to esters and specific glycyl/tauroursodeoxycholate/N-methyl derivatives for “starting seeds.” That tracks likely prior art around bile salt prodrugs, bile acid derivatives, and formulations combining bile acids with digestive enzymes.

Landscape axis 3: enteric polymers that disintegrate under neutral/basic conditions

Most enteric coating systems are acid-resistant and dissolve at higher pH. The specific claim framing is “disintegrates under neutral or basic conditions,” which maps to typical enteric polymers but is also a space where polymer selection and dissolution profiles can be used for design-arounds.

Landscape axis 4: solvent-based granulation with low water

The use of ethanol/propanol/methanol with low water is a specific technical choice. The landscape for low-water alcohol granulation is broader in pharma solid dose manufacturing, but the claim ties it to a particular enzyme-bile salt matrix plus specified excipient combinations. If a competitor uses water-based granulation or different binder-solvent systems, it can avoid one of the hardest claim elements.

Design-around map (based strictly on claim language)

This is a practical infringement assessment map keyed to Claim 1’s literal constraints.

Claim 1 element	Design-around direction	Likely infringement effect
Wetting liquid must be one of three ethanol/propanol/methanol systems with 0.2-2% water	Replace with aqueous granulation or another solvent system not listed	High probability of avoiding literal claim 1(b)
Granulate/extrude through 10 or 18 mesh S/S screen	Use different screen size or different unit operation	High probability of avoiding literal claim 1(c)
Buffering agent + specific base amine band (0.8-5% + 0.8-1.5% within polymer band selection)	Change buffering chemistry or base amine level band	Medium to high probability depending on exact bands
Coating polymer disintegrates under neutral/basic conditions	Use acid-resistant polymer with different release mechanism (e.g., time-controlled, enzymatic cleavage, or non-neutral disintegration)	Medium probability; depends on polymer performance and test data
Must compact into spherical particles	Use different particle morphology manufacturing route	Medium probability; could break literal step requirements

Key Takeaways

US 5,260,074 is built around a process-defined oral dosage form: dry blend of enzyme + ursodeoxycholic acid salt + a constrained buffering system + specific polymers, wetting with a tightly specified alcohol/low-water solvent system, sieve-based granulation, spherical compaction, and acid-resistant coating that disintegrates at neutral/basic pH, ending with dried coated particles.
The claims are most vulnerable to design-arounds that alter (1) the wetting solvent system, (2) mesh screen size, and/or (3) coating disintegration trigger mechanism.
The landscape is likely dense on the high-level product concept (oral enzyme + bile salt) but less crowded on the combination of exact solvent bands + sieve granulation + spherical particle compaction + neutral/basic disintegrating gastric-resistant coating.
Claim 10 creates enforcement leverage only when a challenger can tie the accused product to the claimed manufacturing process for Claim 1 (or the staged route in Claim 8).

FAQs

1) Is US 5,260,074 limited to ursodeoxycholic acid salts only?

Claim 1 is limited to salts of ursodeoxycholic acid. Claim 8 and Claim 9 broaden “starting seeds” to include esters and specific glycyl/tauroursodeoxycholate derivatives, but the process still anchors on ursodeoxycholic acid-related bile salt material.

2) What is the most literal “tripwire” in Claim 1?

The wetting step liquid selection and water banding are the most literal: it must be one of three specified alcohol-based solvent families with 0.2 to 2% water.

3) Does Claim 1 require microspheres?

Claim 3 adds a limitation that the composition is in the form of microspheres with mesh size about 10 to 80, but Claim 1 itself is not limited to microspheres; Claim 1 requires the particle engineering steps culminating in coated spherical particles.

4) Can a competitor avoid infringement by changing the enzyme?

Changing enzyme identity can avoid Claim 2’s enumerated enzymes, but Claim 1 still covers enzymes from broad classes (pancreatic proteases, lipases, nucleases, amylases). Avoidance requires moving outside Claim 1’s enzyme class and related process context.

5) Is Claim 10 enforceable without proving the manufacturing process?

Claim 10 requires administering “the composition of claim 1.” Without tying the marketed product to Claim 1’s process-defined composition, enforcement becomes evidence-heavy, focusing on proof of how the composition was made.

References

[1] United States Patent 5,260,074. (n.d.). Process for preparing a digestive enzyme and bile salt composition and method of treatment. US Patent.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Discure Medical, Llc	CHYMODIACTIN	chymopapain	For Injection	018663	November 10, 1982	5,260,074	2012-06-22
Discure Medical, Llc	CHYMODIACTIN	chymopapain	For Injection	018663	August 21, 1984	5,260,074	2012-06-22
Organon Usa Inc., A Subsidiary Of Merck & Co., Inc.	COTAZYM	pancrelipase	Capsule, Delayed Release	020580	December 09, 1996	5,260,074	2012-06-22
Abbvie Inc.	CREON	pancrelipase	Capsule, Delayed Release	020725	April 30, 2009	5,260,074	2012-06-22
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
United States of America	5578304	⤷ Start Trial
United States of America	5460812	⤷ Start Trial
United States of America	5324514	⤷ Start Trial
European Patent Office	0576938	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 5,260,074

Summary for Patent: 5,260,074