US Patent 9,192,616: Balsalazide With Food Patent Scope, Expiration, Litigation Risk, and Generic Entry Analysis

US Patent 9,192,616 protects specific methods of administering balsalazide with food to alter colonic exposure to balsalazide, 5-aminosalicylic acid, and N-acetyl-5-aminosalicylic acid. It does not claim balsalazide as a chemical compound, balsalazide generally, or every use of balsalazide for ulcerative colitis.

The patent’s practical scope is concentrated in four elements: administration with food, a defined timing window, a pharmacokinetic or colonic exposure result compared with fasting, and particular dosing or labeling instructions. The claims create potential method-of-use and induced-infringement issues for products labeled or promoted for administration with food.

Item	Analysis
Patent	US 9,192,616
Patent type	Utility patent
Technology	Food-effect administration of balsalazide
Active ingredient	Balsalazide, converted principally to 5-ASA and NASA
Primary indication	Gastrointestinal disorders, including ulcerative colitis
Key administration condition	With food, generally 30 minutes before through two hours after food
Principal comparator	Administration in a fasted state
Covered products	Balsalazide capsules, tablets, or other pharmaceutical compositions meeting the claim limitations
Compound protection	No
Core risk	Product labeling, instructions, or conduct that directs administration with food
Generic/biosimilar category	Small-molecule generic, not biologic or biosimilar

What does US Patent 9,192,616 protect?

The independent claims protect treatment methods in which balsalazide is administered with food and produces a specified pharmacokinetic, metabolic, or colonic-transit outcome relative to fasting.

Claim 1 is the principal gastrointestinal-treatment claim. A practicing party must establish:

A subject has a gastrointestinal disorder.
The subject receives a therapeutically effective amount of balsalazide.
Balsalazide is administered with food.
Administration occurs from approximately 30 minutes before food through two hours after food.
Administration with food increases the bioavailability of balsalazide and its metabolites, 5-ASA and NASA, to the colon compared with fasting.

The claim is narrower than a general “take balsalazide with food” instruction. The claimed result is part of the claim. A generic manufacturer or marketer would face a stronger infringement theory if its labeling expressly states that food increases colonic bioavailability or produces one of the claimed metabolic or transit effects.

Claim 24 is a second independent gastrointestinal-treatment claim. It replaces the broader bioavailability limitation with a requirement that administration with food delay 5-ASA transit in the colon compared with fasting.

Claim 13 covers a separate use: inhibiting growth of a bacterial species with a balsalazide composition administered with food. Claims 14 and 15 narrow that use to Clostridium species, including C. perfringens, C. difficile, C. botulinum, and C. tetani.

How do the independent claims differ?

Claim	Protected method	Distinguishing limitation
1	Treating a gastrointestinal disorder	Increased colonic bioavailability of balsalazide, 5-ASA, and NASA compared with fasting
13	Inhibiting bacterial growth	Food administration and increased colonic bioavailability
24	Treating a gastrointestinal disorder	Delayed 5-ASA transit in the colon compared with fasting

Claim 1 is the commercially important claim because it is directed to treatment of gastrointestinal disease and can reach a labeled dosing instruction for ulcerative colitis.

Claim 13 is conceptually broad but commercially less aligned with the FDA-approved use of balsalazide. It depends on a bacterial-growth indication and includes a food-effect limitation. A product marketed only for ulcerative colitis would not automatically practice claim 13.

Claim 24 may be relevant even where a defendant disputes the broader bioavailability limitation in claim 1. Its focus is delayed 5-ASA transit rather than increased overall bioavailability.

What dosing regimens are protected by the patent?

The dependent claims cover several dosing ranges and specific regimens.

Claim	Dose or regimen
4	Approximately 6.25 mg to 14,000 mg/day; 750 mg to 6,750 mg/day; or 1,100 mg to 13,200 mg/day
5	Three 750 mg capsules, three times daily: 6,750 mg/day
6	Three 1,100 mg tablets, twice daily: 6,600 mg/day
7	One 750 mg capsule, three times daily: 2,250 mg/day

The 750 mg capsule regimens are particularly relevant to traditional balsalazide products. The 1,100 mg tablet regimen is relevant to higher-strength or reformulated products.

Claim 4 is drafted with alternative ranges. A product does not need to use every listed range to fall within the claim. The applicable range depends on the administered daily dose and the remaining limitations of claim 1.

The claims do not independently protect the dose without the food-administration and comparative-effect limitations. A 750 mg capsule taken in a fasted state would not satisfy the express food limitation.

What food-timing instructions are covered?

Claims 1, 8, 11, and 12 establish overlapping timing windows:

Claim	Timing requirement
1	Approximately 30 minutes before through two hours after food
8	Approximately 30 minutes before through one hour after food
11	Substantially at the same time as food
12	Immediately after food through approximately one hour after food

Claim 9 identifies applesauce and a high-fat meal as covered food conditions. Claim 17 applies the same food limitation to the bacterial-growth claims.

A label that says “take with food” may create a factual infringement issue if the ordinary meaning of that instruction encompasses the claimed timing window. A label that specifically instructs patients to take balsalazide immediately after a meal or with a high-fat meal presents a more direct risk.

A label directing administration only in a fasted state would generally avoid the express “with food” limitation, although the practical effect of actual patient use could create separate issues in a method-of-use case.

What pharmacokinetic and metabolic outcomes are claimed?

The patent claims several outcomes associated with food administration:

Increased colonic bioavailability of balsalazide, 5-ASA, and NASA.
Increased conversion of 5-ASA to NASA in the colon.
Lower systemic 5-ASA levels.
Increased 5-ASA transit time in the colon.
Increased systemic NASA-to-5-ASA ratio.
Delayed transit of balsalazide or metabolites.
Reduced maximum plasma concentration, or Cmax.
Delayed time to maximum plasma concentration, or Tmax.
Reduced AUC last for 5-ASA or NASA.
Increased conversion of balsalazide to 5-ASA and 5-ASA to NASA.

These limitations give the patent multiple infringement theories but also create proof requirements. The patent owner may need pharmacokinetic evidence, clinical data, product-labeling evidence, or expert testimony to establish that the claimed result occurs.

The comparative nature of the claims is significant. The relevant comparison is not simply whether balsalazide produces colonic exposure. The comparison is whether administration with food produces the specified result relative to administration in a fasted state.

How does the claim language affect infringement analysis?

Literal infringement

A literal infringement case would generally require proof of every limitation in at least one asserted claim. For claim 1, that includes the disease, dose, food timing, and comparative bioavailability result.

The result limitations may be treated as limiting claim language because they describe the physiological consequence required by the method. A defendant could contest infringement by arguing that:

Its label does not direct administration with food.
Its product is administered outside the claimed time window.
The product does not produce the claimed result.
The alleged result has not been demonstrated for the accused formulation.
The patient’s actual conduct does not satisfy the dosing instruction.
The use is outside the claimed gastrointestinal disorder.

Induced infringement

Claim 2 adds an informing step. It requires informing the patient that administration with food increases bioavailability of balsalazide and its metabolites.

This claim is directed to conduct involving patient communication, labeling, counseling, or promotional material. It may be relevant to a manufacturer that supplies instructions directing food administration, although liability would still depend on the full statutory and evidentiary requirements for induced infringement under 35 U.S.C. § 271(b).

A product label can be important evidence because it may show that the manufacturer intended patients to practice the claimed method. FDA-approved labeling, package inserts, medication guides, website content, sales training, and prescriber communications can all become relevant evidence.

What is the patent’s term and expected expiration?

US Patent 9,192,616 issued on November 24, 2015. The enforceable term is generally determined by the earliest effective nonprovisional filing date in the patent family, subject to patent-term adjustment, terminal disclaimers, and any applicable statutory extensions under 35 U.S.C. §§ 154 and 156.

The patent is a later-generation method patent rather than the original compound patent for balsalazide. Its practical exclusivity therefore extends beyond the period in which generic balsalazide products entered the market, but it does not restore exclusivity to the balsalazide molecule itself.

The exact expiration date should be taken from the USPTO patent record and the patent’s continuity and term-adjustment data. The ordinary 20-year term framework places the expected expiration in the late 2020s or early 2030s, depending on the effective filing date and any patent-term adjustment.

What is the Orange Book status of US Patent 9,192,616?

The patent’s claim type creates an Orange Book question distinct from patent validity.

The FDA Orange Book can list patents submitted for an approved drug product and its approved uses. A patent directed to a specific food-administration method may be listed if the NDA holder submits it and FDA accepts the listing. The listing would generally require an associated use code describing the covered method.

The commercial product historically associated with balsalazide is Colazal, marketed by Salix Pharmaceuticals and approved under NDA 20-610. Generic balsalazide products have been approved through ANDA pathways.

The key Orange Book issue is whether the patent was submitted and listed against the relevant NDA and whether an ANDA applicant must make a Paragraph IV certification. Patent status cannot be inferred solely from the patent claims. Orange Book listing records, NDA patent submissions, use codes, and FDA delisting actions control.

A listed method patent can delay approval of an ANDA following a Paragraph IV notice if the NDA holder or patent owner files an infringement action within the statutory period. A patent that is not listed may still support an infringement action, but it would not necessarily trigger the same ANDA approval consequences.

How do Paragraph IV challenges apply?

A generic applicant could challenge the patent through a Paragraph IV certification if the patent is listed in the Orange Book and the applicant asserts that:

The patent is invalid.
The patent is unenforceable.
The proposed product or labeled use does not infringe.

For this patent, likely noninfringement positions would focus on the label and food instructions. A generic applicant could seek a “skinny label” that omits the patented food-related method, assuming the remaining approved uses can be marketed lawfully and the FDA-approved labeling framework permits the omission.

Potential invalidity arguments could include:

Lack of novelty based on prior food-effect studies.
Obviousness based on known balsalazide pharmacology, food-effect testing, and prior dosing instructions.
Lack of written description or enablement for the breadth of the claimed dose, disease, food, and pharmacokinetic combinations.
Indefiniteness involving terms such as “about,” “with food,” “increase,” “delay,” and “substantially at the same time.”
Failure to distinguish the claimed method from routine administration of an oral gastrointestinal drug with meals.

The patent owner would respond that the claimed combination requires a particular food-timing window and a demonstrated, unexpected shift in colonic exposure and metabolite conversion.

What prior balsalazide patents are relevant?

The earlier balsalazide patent estate primarily concerns the compound, prodrug structure, pharmaceutical compositions, and treatment of inflammatory bowel disease. Those patents are distinct from US 9,192,616.

Patent category	Typical subject matter	Relevance to US 9,192,616
Compound patents	Balsalazide and related azo-linked salicylates	Earlier foundational protection; generally expired or near expiration
Composition patents	Capsules, excipients, coatings, and release profiles	May create formulation-specific issues
Treatment patents	Use in ulcerative colitis or inflammatory bowel disease	May overlap commercially but not necessarily claim food administration
Food-effect patent	Administration with food and altered colonic exposure	US 9,192,616’s principal subject
Manufacturing patents	Synthesis, purification, salt formation, and dosage-form manufacture	May affect supply-chain freedom to operate

The existence of earlier expired patents does not eliminate risk under a later method patent. Generic competition can proceed for the compound while remaining exposed to a separately issued method-of-use patent.

What formulation patents and manufacturing barriers remain?

US 9,192,616 is not principally a formulation patent. It does not claim a specific capsule shell, enteric coating, excipient system, particle size, or manufacturing process. Its claims attach to the manner of administration and resulting pharmacokinetics.

A separate freedom-to-operate review should examine:

Balsalazide disodium salt manufacture.
Pharmaceutical-grade purity and impurity controls.
Capsule or tablet release characteristics.
Enteric or colon-targeted delivery systems.
Stability during storage.
Bioequivalence requirements for 750 mg capsules or higher-strength tablets.
Food-effect differences between the reference product and a generic formulation.

Manufacturing patents can create practical barriers even when the composition patent has expired. Those barriers are separate from infringement of US 9,192,616.

What litigation and settlement issues affect the patent?

A complete litigation assessment requires the patent’s current docket history, district-court filings, Federal Circuit activity, PTAB proceedings, and any confidential or public settlement agreements.

The principal litigation questions are:

Whether an ANDA applicant submitted a Paragraph IV certification.
Whether the patent owner filed an infringement complaint within the statutory period.
Whether a court issued a stay of ANDA approval.
Whether the parties entered a license or launch agreement.
Whether the patent was challenged through inter partes review or post-grant review.
Whether the patent has been disclaimed, terminally disclaimed, or narrowed by reexamination.
Whether any settlement permits an authorized generic or an agreed entry date.

No settlement term should be assumed from the existence of a generic balsalazide product. Generic approval and commercial entry can occur because a patent was not listed, was not infringed by the approved label, expired, was licensed, or was successfully challenged.

How strong is the patent estate for balsalazide?

The estate is strongest against a product or label that expressly instructs patients to take balsalazide with food and describes increased colonic bioavailability or delayed metabolite transit.

Risk factor	Assessment
Compound protection	Weak or absent for current commercial purposes because balsalazide compound patents are old
Food-administration method	Material risk where labeling directs administration with meals
Dose-specific claims	Stronger for covered 750 mg and 1,100 mg regimens
Pharmacokinetic result claims	Potentially difficult to prove but commercially meaningful
Bacterial-growth claims	Narrower commercial relevance
Formulation protection	Not the core of US 9,192,616
Generic substitution risk	High if labels omit the patented use; higher litigation risk if labels include food instructions
Biosimilar risk	None; balsalazide is a small molecule
Manufacturing risk	Dependent on separate process and formulation patents

The patent is a method-of-use barrier, not a full market block on balsalazide. A generic manufacturer may be able to sell balsalazide for noninfringing uses if it can omit or avoid the patented food-related instructions.

What generic launch scenarios exist?

Scenario 1: Full-label launch

A generic applicant markets labeling that directs administration with food and includes the claimed pharmacokinetic or therapeutic rationale. This creates the highest infringement exposure.

Scenario 2: Skinny-label launch

The applicant removes the patented food-administration use while retaining noninfringing indications or instructions. This reduces label-based induced-infringement risk but does not eliminate all exposure if actual marketing or conduct encourages the patented method.

Scenario 3: Paragraph IV challenge

The applicant challenges validity, enforceability, or infringement. Litigation may delay approval or produce an agreed launch date, license, or authorized-generic arrangement.

Scenario 4: Post-expiration launch

The applicant waits until patent expiration or a licensed entry date. This eliminates infringement risk under the patent but may sacrifice earlier market access.

How does US 9,192,616 compare with biologic exclusivity?

US 9,192,616 has no biosimilar dimension. Balsalazide is a conventional small-molecule drug regulated through the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

The relevant competitive mechanisms are:

ANDA approval.
Paragraph IV certification.
Label carve-out.
30-month stay, if statutory requirements are met.
Small-molecule patent litigation.
Authorized-generic or licensing arrangements.

Biologics have different reference-product exclusivity and patent-dispute procedures under the Biologics Price Competition and Innovation Act. Those rules do not govern balsalazide.

Key Takeaways

US 9,192,616 claims food-timed administration of balsalazide, not balsalazide itself.
Claim 1 requires administration with food, a defined timing window, and increased colonic bioavailability relative to fasting.
Claim 24 separately targets delayed 5-ASA transit.
Claim 13 covers bacterial-growth inhibition and is commercially narrower than the gastrointestinal-treatment claims.
The patent includes specific 750 mg capsule and 1,100 mg tablet regimens.
Labeling that instructs administration with food creates the principal generic-infringement risk.
A skinny-label strategy may reduce exposure if the patented use can be omitted from the ANDA label.
The patent is a small-molecule method patent, not a biologic patent and not a biosimilar barrier.
Orange Book listing and Paragraph IV consequences depend on FDA patent-submission records, not on the patent claims alone.
The exact enforceable expiration date depends on the patent family’s effective filing date, patent-term adjustment, and any terminal disclaimer.

FAQs About US Patent 9,192,616

Does US 9,192,616 prevent generic balsalazide from being sold?

No. It does not claim balsalazide as a compound. It may restrict a generic product’s labeled or promoted use if the product directs administration with food in a manner covered by the asserted claims.

Is taking balsalazide with food automatically patent infringement?

Not automatically. Infringement would depend on the asserted claim, the patient’s conduct, the timing of administration, the disease being treated, the dose, and whether the claimed comparative pharmacokinetic result is established.

Does the patent cover Colazal specifically?

The claims are directed to methods using balsalazide and can cover a Colazal product if the product is administered in the claimed manner. The patent does not claim the COLAZAL trademark or a particular manufacturer’s product by name.

Can a generic manufacturer omit the food instructions from its label?

Potentially. A label carve-out may avoid the patented method if the FDA-approved labeling permits omission and the manufacturer does not otherwise promote or encourage the carved-out use.

Does the patent cover balsalazide taken with applesauce?

Claim 9 expressly identifies applesauce as a food condition. The remaining limitations of the underlying claim, including timing and the claimed comparative result, still apply.

Sources

United States Patent and Trademark Office. (2015). United States Patent No. 9,192,616, methods of treating gastrointestinal disorders.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (n.d.). COLAZAL (balsalazide disodium) prescribing information.
21 U.S.C. § 355.
35 U.S.C. §§ 154, 156, 271.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Valeant Pharms Intl	GIAZO	balsalazide disodium	TABLET;ORAL	022205-001	Feb 3, 2012		DISCN	Yes	No	9,192,616	⤷ Start Trial				TREATMENT OF MILDLY TO MODERATELY ACTIVE ULCERATIVE COLITIS IN MALE PATIENTS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006282865	⤷ Start Trial
Australia	2007322362	⤷ Start Trial
Brazil	PI0615195	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,192,616

Which drugs does patent 9,192,616 protect, and when does it expire?

Summary for Patent: 9,192,616