Patent: 5,750,104

Summary for Patent: 5,750,104

Title:	High buffer-containing enteric coating digestive enzyme bile acid compositions and method of treating digestive disorders therewith
Abstract:	Disclosed are gastric acid-resistant polymer-coated buffered digestive enzymes/bile acid compositions, process for their preparations and methods of treating digestive disorders and cystic fibrosis by administering said compositions to a mammal in need of such treatment.
Inventor(s):	Tibor Sipos
Assignee:	Digestive Care Inc
Application Number:	US08/654,900
Patent Claims:	see list of patent claims

United States Patent 5,750,104 Patent Claims and Landscape (Microencapsulated Buffered Digestive Enzyme Compositions)

Executive summary: U.S. Patent 5,750,104 claims a tightly specified, microencapsulated oral particulate system for “digestive enzyme/buffer deficiency” and “digestive enzyme-bile acid-buffer deficiency,” anchored on (i) a defined enzyme concentration range, (ii) a high loading of buffering agent (45–60% w/w) that drives small-intestinal pH to 7–9, (iii) a lipase activity requirement at that pH (24–100% at pH 7–9), (iv) a disintegrant and adhesive polymer system, and (v) an enteric, gastric-resistant, non-porous polymer coating with strict talc and pH-solubility constraints, plus a particle-size window (10 mesh to 40 mesh). The enforceable core is the combination of composition variables with functional pH and lipase-activity performance features, which narrows literal coverage and increases validity and design-around leverage for would-be entrants. The claim set also expands to include a method of treating deficiency conditions (claim 4) with a downstream “condition” clause (claim 5), which is likely to face obviousness and subject-matter/enablement pressure if the underlying composition disclosures do not clearly support the full medical scope.

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What does US Patent 5,750,104 claim protect: microencapsulated buffered digestive enzyme and bile acid compositions?

Short answer: The patent protects an oral, microencapsulated particle formulation (10 mesh to 40 mesh) that couples digestive enzymes with high-load buffering agents to maintain small-intestinal pH 7–9, with an enteric, pH-selective polymer coating, plus defined excipient classes (disintegrant + adhesive polymer) and, in one claim set, a micropulverized buffered bile acid component at a 1:1 neutralization-equivalent ratio.

Claim 1: “digestive enzyme/buffer deficiency” composition

Key claim constraints (literal):

• Particle size: microencapsulated particles, 10 mesh to 40 mesh
• Enzymes (w/w): 10–70% of an enzyme selected from pancreatic proteases, lipases, nucleases, amylases
• Disintegrant (w/w): 0.5–16% selected from ursodiol, starch, modified starches, microcrystalline cellulose, propylene glycol alginate
• Adhesive polymer (w/w): 1–19% selected from polyvinylpyrrolidone, hydroxypropyl cellulose, cellulose acetate phthalate, ethyl cellulose, hydroxypropylmethyl cellulose
• Gastric-resistant coating (w/w): 7–25% of a non-porous enteric polymer coating:
  • <2% talc
  • insoluble pH 1.5–5
  • soluble pH 5.5–9
  • polymer species limited to: hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, diethyl phthalate, dibutyl phthalate, enteric coating polymeric dispersion, acrylic-based polymeric dispersion
• “Improvement consisting essentially of” core performance payload:
  • buffering agent (w/w): 45–60%
  • buffering agent selected from anhydrous sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, ammonium carbonate, tromethamine, di(tris(hydroxymethyl)aminomethane)carbonate, tris-glycine, di-arginine, tri-arginine, poly-arginine, di-lysine, tri-lysine, poly-lysine, diethylamine, triethanolamine
  • buffering agent provides pH 7–9 in the small intestine
  • lipase activity requirement: lipase has activity 24–100% at pH 7–9

Criticality for enforceability: “selected enzyme” + performance features

• The claim is written so the enzyme component is “selected from” pancreatic proteases, lipases, nucleases, amylases, but the improvement clause explicitly requires lipase activity at pH 7–9. This creates interpretive pressure on how a competitor that uses protease-only would satisfy the lipase condition, and it also makes performance data central to validity and infringement proof.

Claim 2: “digestive enzyme-bile acid-buffer deficiency” composition (buffered bile acid addition)

Added elements vs claim 1:

• Bile acid/buffer powder: from 0.1–15% w/w micropulverized, buffered bile acid
• Must form a buffer/bile acid mixture at a 1 to 1 neutralization equivalent ratio (with buffer selected from the same buffering-agent list)

Claim 3: narrows claim 2 by specifying 0.25–10% of the buffered bile acid component.

Claim 4: method of treatment using the claimed composition

Claim structure:

• orally administer effective amount of the composition of claim 1 (as recited) for “digestive enzyme, bile acid and buffer deficiency in a mammal”
• includes the same formulation architecture and improvement payload as in claim 1/2

Claim 5: narrows the indication set

• treatment is to reduce/modify conditions including:
  • digestive enzyme deficiency, digestive disorders
  • impaired liver function
  • cystic fibrosis
  • presence of gallstones

Enforcement impact:

• The method claim is only as strong as the composition claims it incorporates. If formulation variables are avoided or materially altered, method coverage collapses.
• Indication breadth (“digestive disorders,” “impaired liver function,” “gallstones”) raises obviousness and enablement risk if the specification and prosecution record do not anchor those outcomes to the claimed formulation’s demonstrated mechanism.

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How strong are the patent claims: which elements are likely to be the enforceable core vs easy to design around?

Short answer: The enforceable “core” is the constrained combination of (i) the 45–60% buffering agent plus pH 7–9 small intestine plus lipase activity 24–100%, with (ii) the enteric non-porous polymer coating insoluble at pH 1.5–5 but soluble at pH 5.5–9 and <2% talc, all within a narrow particle-size window and excipient classes.

Likely enforceable core (harder to design around)

1. Buffering agent loading and functional pH
   • 45–60% w/w buffering agent with pH 7–9 requirement creates a measurable performance lever. Competitors can avoid literal infringement by changing buffer chemistry, reducing buffer load, or altering resulting pH profile.
2. Lipase activity at pH 7–9
   • This is a functional parameter. In litigation, it drives both infringement testing and validity attacks on written description/enablement if the patent does not provide reproducible methods and data.
3. Coating constraints
   • “Non-porous,” “insoluble pH 1.5–5,” “soluble pH 5.5–9,” and “<2% talc” together tightly define the coating system. The polymer list is limited, which helps claim construction and makes substitutions likely to be non-literal.

Likely weak spots (easier to attack or work around)

1. “Improvement consisting essentially of”
   • This transitional phrase is a partial escape hatch for accused products that add ingredients not materially affecting the basic and novel characteristics. If the specification identifies a limited “basic and novel” set (likely buffer + enteric pH-release performance + particle architecture), a defendant can argue non-material additives preserve the “consisting essentially of” boundary while escaping literal recitation.
2. Enzyme selection ambiguity
   • Claim 1 includes enzymes “selected from” a list, but still demands lipase activity at pH 7–9. If a competitor’s formulation uses proteases but not lipase, the defendant would argue the “lipase activity” limitation is not satisfied. The patentee would likely argue that lipase is inherently present or required, but the text as drafted creates an infringement dispute pathway.
3. Particle size (10 mesh to 40 mesh)
   • Particle sizing is measurable. Competitors can shift particle size distribution outside this window while maintaining similar performance.
4. Excipients are constrained to “selected from” lists
   • For disintegrants and adhesive polymers, competitors can use different excipients or different coating polymers outside the recited list to move outside literal coverage.

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What patents and earlier art typically collide with claims like these: microencapsulation, enteric coatings, digestive enzyme stabilization, and small-intestine pH control?

Short answer: The claim architecture maps onto common prior-art families: (i) microencapsulated digestive enzyme compositions, (ii) enteric coating systems tuned for gastric resistance and small-intestinal solubility, (iii) buffered enzyme formulations to preserve activity in intestinal pH, and (iv) bile acid or bile salt incorporation for pancreatic enzyme delivery. The novelty likely relied on the specific combination of the high buffer loading (45–60%), particular buffer species set, defined pH 7–9 performance, lipase activity at that pH, and the coating talc and pH solubility constraints within the 10–40 mesh particle window.

How to read the claim for prior-art designates

• If earlier patents disclose microencapsulated enzymes with enteric coatings and buffers, they may anticipate broad elements.
• The differentiators for novelty/defensibility are:
  • buffer amount range
  • functional pH range in the small intestine
  • lipase activity at that pH range
  • coating “non-porous” + pH-solubility window + <2% talc
  • specific polymer species list
  • particle mesh window

Key litigation/validity risk pattern

If the specification and prosecution history do not tie these features to comparative performance over the closest prior art, claim 1’s “improvement” could be vulnerable to obviousness combining known buffered enzyme stabilizers with known enteric microencapsulation and known bile-acid powders.

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When does US Patent 5,750,104 expire, and what does that mean for generic or copycat risk?

Short answer: U.S. Patent 5,750,104 is a late-1990s filing era patent. Its practical exclusivity tail is driven by filing date, any patent term adjustments, and whether it is subject to any regulatory-related PTA/extension. Without filing- and maintenance-level data, no reliable expiration date can be stated from claim text alone.

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What Orange Book status exists for U.S. Patent 5,750,104, and how does it affect FDA generic entry?

Short answer: Orange Book listings depend on whether the patent is listed for a specific NDA/ANDA product. The claim text alone does not identify the referenced active ingredient drug product, dosage form, or listed NDA number. Without that linkage, no definitive Orange Book status can be produced.

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What would a Paragraph IV challenge or FDA generics strategy look like against this claim set?

Short answer: A Paragraph IV strategy would focus on breaking literal infringement by targeting the most measurable constraints:

• change buffering agent concentration below 45% or above 60%
• change buffer species outside the listed group
• shift effective pH so the small intestinal pH is not 7–9
• replace lipase with other enzymes or use lipase but demonstrate activity outside 24–100% at pH 7–9
• substitute the enteric polymer coating with a system not meeting <2% talc and/or not insoluble at pH 1.5–5 or not soluble at pH 5.5–9
• adjust particle size distribution outside 10–40 mesh

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How do the claims map to potential biosimilar risk or biologics vs small-molecule generics?

Short answer: The patent is for enzyme compositions, which are typically treated as drug products but not “biologics” in the biosimilar framework unless licensed under the biologics pathway and meet the biosimilar definition. Patent text does not establish pathway status. From a claim-structure perspective, the formulation is more aligned with conventional generic small-molecule formulation entry than biosimilar pathway risk.

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How many claim “landing zones” exist: composition claims vs method claims vs narrower bile acid subclass?

Short answer: There are at least three actionable layers:

1. Claim 1 broad buffered enzyme composition (with lipase activity at pH 7–9)
2. Claim 2 adds buffered bile acid at 0.1–15% with 1:1 neutralization ratio
3. Claim 3 narrows the bile acid amount to 0.25–10%
4. Claim 4 method of treatment incorporating the full composition constraints
5. Claim 5 narrows indication targets

Litigation implication: Defendants often aim to knock out the base composition (claim 1) to collapse method coverage, while plaintiffs may pursue dependent narrowing (claim 2/3) as a fallback if claim 1 is invalid or avoided.

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What formulation design changes likely avoid infringement while keeping clinical intent?

Short answer: To avoid literal infringement, a designer would typically change at least one “hard” limitation rather than try to maintain everything else. The most direct are:

• Buffer loading outside 45–60% w/w
• Buffer chemistry outside the listed set
• Coating polymer outside the listed set or altering solubility profile or porosity/talc
• Particle mesh outside 10–40
• Remove lipase or adjust lipase activity profile outside 24–100% at pH 7–9
• For claim 2/3: alter buffered bile acid neutralization equivalence ratio away from 1:1 or change micropulverized buffered bile acid amount outside ranges

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Key Takeaways

• U.S. Patent 5,750,104 is built around a constrained microencapsulated particulate oral formulation with a high-load buffering system that drives small-intestinal pH to 7–9 and a measurable lipase activity window at that pH.
• The coating system is a major enforceability pillar: “non-porous,” limited talc, and strict insolubility/solubility pH ranges, plus limited polymer species.
• The bile-acid extension (claims 2–3) adds a second measurable dimension: micropulverized buffered bile acid at specified w/w and a strict 1:1 neutralization-equivalent ratio.
• The method claims are derivative of the composition claims; avoiding composition limitations likely ends method coverage.
• From a risk perspective, the most straightforward infringement “levers” are buffer loading/pH performance, lipase activity, coating pH behavior and talc content, and particle mesh size.

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FAQs

1. Does claim 1 require lipase specifically, even though “enzyme” is selected from proteases, lipases, nucleases, and amylases?
2. How does “insoluble in pH 1.5–5 but soluble in pH 5.5–9” get tested in infringement or validity disputes?
3. Can a product add other excipients and still fall under “consisting essentially of” in claim 1?
4. What is the infringement risk difference between claim 2 (buffered bile acid) and claim 1 (buffer-only deficiency) products?
5. If a competitor shifts particle size distribution outside 10–40 mesh, does it avoid both composition and method coverage?

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References

No external sources were cited because no patent bibliographic data, filing date, assignee, prosecution history, or related patent citations were provided beyond the claim text itself.

Details for Patent 5,750,104

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Digestive Care, Inc.	PERTZYE	pancrelipase	Capsule, Delayed Release	022175	May 17, 2012		2016-05-29
Digestive Care, Inc.	PERTZYE	pancrelipase	Capsule, Delayed Release	022175	October 6, 2016		2016-05-29
Digestive Care, Inc.	PERTZYE	pancrelipase	Capsule, Delayed Release	022175	July 13, 2017		2016-05-29

International Patent Family for US Patent 5,750,104

Country	Patent Number	Estimated Expiration
Canada	2228389