Details for Patent: 8,741,948

Summary for Patent: 8,741,948

Title:	Oral antimicrobial pharmaceutical compositions
Abstract:	The present invention relates to oral pharmaceutical compositions with controlled and/or programmed release containing at least one active ingredient having antimicrobial and/or anti-infectious activity for the treatment of infections of the large intestine, in particular the colon.
Inventor(s):	Mauro Ajani, Roberta Bozzella, Giuseppe Celasco, Roberto Villa
Assignee:	Cosmo Technologies Ltd
Application Number:	US13/592,088
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Executive summary
US Patent 8,741,948 claims controlled-release oral tablet compositions of rifamycin SV designed to remain gastro-resistant in simulated gastric/acidic environments and to release rifamycin SV in a controlled manner in phosphate buffer at pH 7.2 (less than 20% released at ~1 hour; more than 70% released at ~8 hours). The independent scope is defined by (i) a homogeneous tablet core containing rifamycin SV plus hydrophilic, lipophilic, and amphiphilic excipients, and (ii) a coating comprising a gastro-resistant substance, with explicit quantitative rifamycin SV loading (about 10% to about 90% by weight) and explicit in vitro release/disintegration performance constraints. Dependent claims further narrow dissolution resistance at pH 1 and pH 6.4, excipient identity/subclasses (e.g., lecithin; methacrylic-acid polymers; carboxyvinyl polymers/copolymers; select cellulose derivatives; optional sodium salt form), and treatment use focused on large intestine infections including infectious colitis, bacillary dysentery, pseudomembranous colitis, traveler’s diarrhea, diverticular disease and diverticulitis.

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United States Patent 8,741,948 rifamycin SV gastro-resistant controlled release scope: claims, allowable variants, and competitor design-around risk

US 8,741,948 is a formulation-and-method patent that ties rifamycin SV controlled-release performance to a specific tablet architecture: a homogeneous multi-excipient core plus a gastro-resistant coating layer. In enforcement terms, the claim set is strongest against oral solid dosage competitors that keep rifamycin SV protected in acidic conditions and deliver rifamycin SV into the intestinal environment with the claimed release curve.

What does US 8,741,948 claim for rifamycin SV controlled release oral tablets?

Core limitations that define infringement risk

1. Dosage form/structure: a controlled-release oral pharmaceutical composition comprising
   • (1) tablet core that is “homogeneous” and includes rifamycin SV + hydrophilic + lipophilic + amphiphilic substances, and
   • (2) coating on the tablet core with a gastro-resistant substance.
2. Quantitative drug loading: rifamycin SV from about 10% to about 90% by weight.
3. Performance envelope at pH 7.2 (buffer release test):
   • < ~20% released after ~1 hour and
   • > ~70% released after ~8 hours.
     These performance parameters are claim elements, not post hoc evidence. A product that fails these thresholds is outside the independent claim as written.

Claim 1 is not limited to a specific carrier “recipe,” but it is limited to functional categories and quantitative performance.

What is “gastro-resistant substance” in claim scope?

Claim 1 requires a coating with a gastro-resistant substance. Dependent claim 12 specifies one preferred class:

• gastro-resistant substance comprises at least one methacrylic acid polymer.
  That dependent claim narrows toward common enteric coating polymers (Eudragit-type materials). Competitors using different enteric polymers may still fall under claim 1 if their coating meets the “gastro-resistant” limitation and achieves the claimed release curve.

How broad are the excipient definitions in claim 1?

Claim 1 uses three excipient “types” plus a gastro-resistant coating:

• Hydrophilic substance
• Lipophilic substance
• Amphiphilic substance
• Gastro-resistant substance (coating)

What specific excipient embodiments are explicitly listed in dependent claims?

Dependent claims enumerate examples that act as both claim coverage signals and drafting “anchor points.”

Hydrophilic substances (claim 10)

• carboxyvinyl polymers, carboxyvinyl copolymers
• hydroxyalkyl celluloses, alkyl celluloses, carboxyalkyl celluloses
• polysaccharides, pectins
• hyaluronic acid, glucuronic acid, glucosamines

Further narrowing (claim 11)

• hydrophilic chosen from carboxyvinyl polymers and carboxyvinyl copolymers.

Amphiphilic substance (claim 9)

• amphiphilic comprises lecithin.

Lipophilic substance (claim 8)

• lipophilic has melting point < ~90°C.

Gastro-resistant coating (claim 12)

• coating comprises at least one methacrylic acid polymer.

What can a competitor change while staying inside the claims?

Given the broad categorical language (“chosen from at least one of…”, “comprises”), a design can retain infringement risk by:

• keeping the four-part core architecture (rifamycin SV + hydrophilic + lipophilic + amphiphilic),
• preserving “homogeneous” core character (practically, avoiding phase-separated layered cores),
• using a gastro-resistant coating that delivers the same release behavior at pH 7.2 and acidic resistance.

However, explicit quantitative and performance thresholds create hard stop lines for many design modifications.

What are the key release and dissolution performance thresholds that drive coverage?

The claims repeatedly tie infringement to in vitro release rates and dissolution resistance.

pH 7.2 release curve constraints (claim 1 and claim 2)

• Claim 1:
  • < ~20% released after ~1 hour
  • > ~70% released after ~8 hours
• Claim 2:
  • < ~50% released after ~3 hours

These give a time-based shape requirement: limited early release and robust later release.

Acid resistance constraints (claims 3 to 5)

• Claim 3: resistant to dissolution in an acidic environment (broad functional statement).
• Claim 4: resistant to dissolution for 2 hours at pH 1.
• Claim 5: resistant to dissolution for 1 hour at pH 6.4.

These are narrower functional constraints tied to specific pH values and time durations.

How do these thresholds affect design-around decisions?

A competitor seeking to avoid claim 1 coverage would need a product that fails at least one element, commonly by:

• altering the release curve such that at pH 7.2 it releases ≥20% by ~1 hour or ≤70% by ~8 hours, or
• altering acid/dissolution resistance so that pH 1 or pH 6.4 dissolution time requirements are not met (especially if claim 4 or 5 are asserted), or
• changing the core architecture (e.g., removing one required excipient function category, or avoiding a “homogeneous” structure as argued in claim construction).

Because these are performance claims, enforcement often hinges on comparative dissolution testing using the same or substantially similar protocols.

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What patent claim language covers methods treating large intestine infections with rifamycin SV?

Claim 13 and dependent claims convert the formulation into a method-of-treatment for “infection of the large intestine.” The treatment recitations incorporate the same composition limitations and performance requirements.

What large intestine indications are listed in the claim set?

Claim 25 lists examples:

• infectious colitis
• bacillary dysentery
• pseudomembranous colitis
• traveller’s diarhoea
• diverticular disease
• diverticulitis

Claim 26 adds:

• traveller’s diarhoea.

The presence of these indication examples matters for enforcement strategy: a sponsor marketing for any of these indications with an allegedly infringing product can better anchor method claim theories.

How much additional scope do dependent method claims add?

Dependent method claims 14 to 24 mirror composition performance and embodiment limitations:

• Claim 14: <50% released after ~3 hours at pH 7.2.
• Claims 15-17: acid and pH dissolution resistance (acidic environment; pH 1 for 2 hours; pH 6.4 for 1 hour).
• Claims 18-24: rifamycin loading range; sodium salt form; lipophilic melting point; lecithin amphiphile; hydrophilic excipient lists; methacrylic acid polymer coating.

In practical licensing and litigation, the method claim is often asserted alongside composition claims, and the dependent scope becomes a fallback ladder.

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How many patentable claim categories are in US 8,741,948: composition vs method vs performance-defined limitations?

At a high level, the patent comprises two linked claim clusters:

1. Composition claims (1-12)
   • independent claim 1 defines the tablet core + coating + drug loading + pH 7.2 release profile
   • dependent claims add performance timepoints, dissolution resistance, and excipient identities
2. Method claims (13-26)
   • independent claim 13 ties the same composition limitations to treating large intestine infection
   • dependent claims narrow the same way with release/dissolution/excipient specifics and explicit indication examples

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What is the likely functional “core + enteric coating + in vitro release profile” claim meaning for claim construction?

The claim construction battleground typically centers on whether the accused product:

• uses a “homogeneous structure” core,
• includes the required excipient categories, and
• meets both the early and late release thresholds at pH 7.2 plus the dissolution resistance at pH 1 and/or pH 6.4.

How does “homogeneous structure comprising” affect infringement?

“Homogeneous structure” implies non-layered, uniform distribution. Competitors using multi-layer cores or segregated drug domains may argue lack of “homogeneous” structure. But in practice, most conventional tablet matrices are “homogeneous” in the sense of uniform drug distribution.

How does “provides an in vitro release rate… in buffer at pH 7.2” affect enforcement?

This is a quantized performance requirement. Litigation testing often becomes central:

• dissolution apparatus, agitation speed, medium composition, sample times (about 1 hour, about 3 hours, about 8 hours) and whether endpoints match the “about” ranges.

Even if “about” provides some latitude, a large shift in the curve typically moves the product outside the stated thresholds.

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What generic entry risks exist for rifamycin SV controlled-release large-intestine products?

US 8,741,948 creates entry risk mainly for oral controlled-release tablet candidates aiming to treat large intestine infections using rifamycin SV with:

• enteric/gastro-resistant coatings, and
• delayed but substantial release into pH 7.2 conditions.

Where would generic or follow-on products be most likely to face patent exposure?

• Controlled-release enteric-coated rifamycin SV tablets for large intestine indications.
• Formulations that rely on methacrylic acid polymers and conventional excipient categories overlapping with hydrophilic/lipophilic/amphiphilic components.

Where are the higher-likelihood avoidance paths?

Avoidance would likely require one or more of:

• changing the release curve so it fails claim 1 thresholds at pH 7.2,
• changing coating dissolution behavior so it fails pH 1 and/or pH 6.4 dissolution time requirements,
• altering tablet architecture so the core is not “homogeneous” in the claim sense, or
• eliminating one required excipient category as argued under claim construction (e.g., amphiphile not present in the required way), while still maintaining a viable product.

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What formulations are explicitly protected by US 8,741,948?

Protected formulations are defined both by composition content and by functional performance.

Protected drug form and loading

• Rifamycin SV as the active.
• Optional dependent coverage for sodium salt form.
• Drug loading in 10% to 90% by weight (claim 1 and dependent claim 18 narrows to 20%-60%).

Protected excipient classes

• Hydrophilic: broad polymer/cellulose/pectin/sugar-acid family list.
• Lipophilic: melt point < 90°C.
• Amphiphilic: lecithin.
• Gastro-resistant coating: methacrylic acid polymers (dependent claim 12).

Protected dissolution and release behavior

• Acid resistance: stable for 2 hours at pH 1 (claim 4) and 1 hour at pH 6.4 (claim 5).
• pH 7.2 release curve: <20% after ~1 hour and >70% after ~8 hours (claim 1), plus <50% after ~3 hours (claim 2).

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What does the patent protect relative to rifamycin SV “enteric” and “controlled release” competitors?

The claim language positions the patent at the intersection of:

• delayed intestinal delivery (enteric/gastro-resistant coating),
• sustained release (controlled-release performance),
• multi-excipient core design (homogeneous matrix with hydrophilic/lipophilic/amphiphilic components).

Likely comparison buckets for competitor products

1. Enteric-coated immediate-release rifamycin SV
   • risk if release at pH 7.2 matches claim curve.
2. Extended-release matrix rifamycin SV without enteric gastro-resistance
   • risk reduced if pH 1 and pH 6.4 dissolution resistance fails.
3. Multiparticulate pellets filled into capsules
   • possible non-infringement if not a “tablet core” with “tablet core” architecture and coating as claimed.
4. Alternative coatings and release mechanisms
   • risk depends on whether the pH 7.2 release curve and acid dissolution resistance are achieved.

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What other patents might matter around US 8,741,948?

No other patent numbers, assignees, family members, continuation status, or citation data were provided with the input. Without those, a complete landscape mapping cannot be produced from the information given.

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Key Takeaways

• US 8,741,948 is a formulation-and-method patent centered on a rifamycin SV controlled-release oral tablet with a homogeneous core (hydrophilic + lipophilic + amphiphilic) and a gastro-resistant coating.
• Infringement is tied to hard performance thresholds: at pH 7.2, <20% released at ~1 hour and >70% released at ~8 hours; dependent claims further cap release at ~3 hours and require dissolution resistance at pH 1 (2 hours) and pH 6.4 (1 hour).
• Excipient lists narrow dependent coverage (lecithin amphiphile; methacrylic acid polymer coating; specific hydrophilic polymer/cellulose/pectin families; lipophilic melt point <90°C).
• Method claims target large intestine infections, including infectious colitis, bacillary dysentery, pseudomembranous colitis, traveler’s diarrhea, diverticular disease and diverticulitis.
• For market entry planning, the main risk zone is enteric/controlled-release rifamycin SV tablets whose dissolution and release profiles match the claim curve; design-around typically requires breaking at least one performance threshold or the claimed structural elements.

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FAQs

1) Does US 8,741,948 require methacrylic acid polymers to infringe?
No. Methacrylic acid polymers are recited in dependent claim 12; claim 1 only requires a gastro-resistant coating that meets the performance and structural limitations.

2) Can a product with different rifamycin SV loading avoid claim 1?
Potentially. Claim 1 requires about 10% to about 90% by weight rifamycin SV; claim 18 narrows to about 20% to about 60%.

3) What is the fastest “litigation-relevant” metric for comparing an accused product to claim 1?
The pH 7.2 release curve near the claimed timepoints: <20% at ~1 hour and >70% at ~8 hours.

4) Are the method-of-treatment claims limited to specific listed infections?
The claim recites “infection of the large intestine” in claim 13; dependent claims 25 and 26 enumerate example indications like traveler’s diarrhea.

5) Does “acidic environment” in claim 3 replace the specific pH 1 and pH 6.4 limitations?
Claim 3 is broader, while claims 4 and 5 specify pH 1 (2 hours) and pH 6.4 (1 hour). A product can still be exposed under the narrower dependent limitations if it fails those specific dissolution resistance thresholds.

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References (APA)

1. United States Patent 8,741,948. Controlled release oral pharmaceutical composition comprising rifamycin SV and methods of treating large intestine infections.

Drugs Protected by US Patent 8,741,948

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: 8,741,948

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	MI2004A1295	Jun 25, 2004

International Family Members for US Patent 8,741,948

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1763339		122019000048	Germany
European Patent Office	1763339		C201930053	Spain
European Patent Office	1763339		SPC/GB19/037	United Kingdom
Austria	E392889
Canada	2569683