Details for Patent: 8,110,553

Summary for Patent: 8,110,553

Title:	Methods and compositions for the treatment of gastrointestinal disorders
Abstract:	The present invention features compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), Crohn's disease, ulcerative colitis, Inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation (post-operative ileus), and constipation associated with neuropathic disorders as well as other conditions and disorders using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.
Inventor(s):	Mark G. Currie, Shalina Mahajan-Miklos, G. Todd Milne, Thea Norman
Assignee:	Ironwood Pharmaceuticals Inc
Application Number:	US12/788,979
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,110,553
Patent Claim Types: see list of patent claims	Use;

US Patent 8,110,553: Linaclotide Claim Scope, Expiration, Litigation and Patent Landscape

US Patent 8,110,553 protects methods of treating gastrointestinal disorders with linaclotide, the 13-amino-acid guanylate cyclase-C agonist marketed as Linzess. Its independent claims cover increasing intestinal motility and treating gastrointestinal disorders. The claims specifically reach chronic constipation, opioid-induced constipation, constipation-predominant irritable bowel syndrome and alternating irritable bowel syndrome.

The patent is a method-of-use patent, not a composition-of-matter patent. Its commercial relevance depends on the overlap between the claimed uses and FDA-approved Linzess indications, the patent’s Orange Book status, related formulation patents, and any generic settlement or license terms.

What peptide does US Patent 8,110,553 protect?

The claimed peptide is linaclotide, identified in the patent as SEQ ID NO:125:

Cys-Cys-Glu-Tyr-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys

The sequence is also represented as:

CCEYCCNPACTGC

Linaclotide is a disulfide-bonded peptide agonist of guanylate cyclase-C, or GC-C. GC-C activation increases intracellular cyclic guanosine monophosphate in intestinal epithelial cells. The resulting signaling increases intestinal fluid secretion and promotes intestinal transit. The FDA-approved product is linaclotide, supplied in oral capsules at 72 mcg, 145 mcg and 290 mcg strengths.[1]

Claim element summary

Claim	Legal category	Principal scope
1	Independent method claim	Administering an effective amount of a peptide comprising SEQ ID NO:125 to increase intestinal motility
2	Dependent method claim	Peptide consists of SEQ ID NO:125
3	Independent method claim	Administering an effective amount of a peptide comprising SEQ ID NO:125 to treat a gastrointestinal disorder
4	Dependent method claim	Peptide consists of SEQ ID NO:125
5	Dependent method claim	Listed gastrointestinal disorders, including IBS, constipation, GERD, dyspepsia and gastroparesis
6	Dependent method claim	Constipation
7	Dependent method claim	Chronic, idiopathic, postoperative-ileus or opioid-induced constipation
8	Dependent method claim	Chronic constipation
9	Dependent method claim	Irritable bowel syndrome
10	Dependent method claim	Constipation-predominant IBS
11	Dependent method claim	Alternating IBS

How broad are the independent claims in US 8,110,553?

Claims 1 and 3 are broad relative to the dependent claims because they do not limit the treatment to a named gastrointestinal disorder, dosage form, dose, route or patient subgroup.

Claim 1 requires:

1. A patient.
2. Administration of an effective amount.
3. A peptide comprising the claimed 13-residue sequence, or a pharmaceutically acceptable salt.
4. An increase in intestinal motility.

Claim 3 requires:

1. A patient.
2. Administration of an effective amount.
3. A peptide comprising the claimed sequence, or a pharmaceutically acceptable salt.
4. Treatment of a gastrointestinal disorder.

The claims do not expressly require:

• Oral administration.
• A capsule.
• A particular dosage strength.
• A specific dosing frequency.
• A particular disulfide-bond configuration.
• A particular manufacturing process.
• A specific patient age.
• A particular formulation excipient.

That omission gives the independent claims potentially broad coverage over any qualifying administration method, subject to the ordinary requirements of claim construction, enablement, written description and infringement proof.

What does “comprising” mean in claims 1 and 3?

“Comprising” is an open-ended transition. A peptide that contains the claimed sequence could fall within the literal language of claims 1 and 3 even if it has additional amino acids or additional structural elements, provided the accused peptide still satisfies the remaining claim limitations.

Claims 2 and 4 are narrower. They require that the peptide “consists of” SEQ ID NO:125. Those claims are directed to the exact linaclotide peptide sequence, subject to the claim’s express reference to a pharmaceutically acceptable salt.

The practical distinction is important:

Language	Potential reach
“Comprising SEQ ID NO:125”	Peptides containing the sequence, including potentially modified or extended peptides
“Consists of SEQ ID NO:125”	The exact 13-amino-acid peptide
“Or a pharmaceutically acceptable salt thereof”	Salt forms of the claimed peptide

What medical uses does US Patent 8,110,553 cover?

The patent covers a broad set of gastrointestinal indications through claims 3 through 11.

Expressly listed gastrointestinal disorders

Claim 5 identifies:

• Irritable bowel syndrome.
• Constipation.
• Gastrointestinal motility disorders.
• Gastroesophageal reflux disease.
• Functional heartburn.
• Dyspepsia.
• Gastroparesis.
• Chronic intestinal pseudo-obstruction.
• Colonic pseudo-obstruction.

The claim uses a closed “selected from the group consisting of” formulation. That language narrows claim 5 to the listed disorders. Claim 3 remains broader because it covers treatment of a gastrointestinal disorder without using the claim 5 list.

Constipation claims

Claims 6 through 8 create a focused hierarchy:

• Claim 6 covers constipation.
• Claim 7 covers chronic constipation, idiopathic constipation, postoperative-ileus constipation and opioid-induced constipation.
• Claim 8 narrows the scope to chronic constipation.

The opioid-induced and postoperative-ileus limitations are commercially relevant because they identify patient populations beyond the two core FDA-approved Linzess indications.

IBS claims

Claims 9 through 11 cover:

• IBS generally.
• Constipation-predominant IBS, commonly abbreviated IBS-C.
• Alternating IBS.

The FDA-approved IBS-C indication corresponds directly to claim 10’s disease category. The claim is not limited to the 290 mcg dose used for adults with IBS-C. The relevant dose and administration instructions come from the approved labeling rather than the patent claims.[1]

What is the FDA regulatory status of linaclotide?

The FDA approved Linzess on August 30, 2012, for adults with IBS-C and chronic idiopathic constipation.[2] The approved indications were later expanded to include pediatric patients ages 6 to 17 with functional constipation. The FDA labeling identifies linaclotide as a GC-C agonist and includes a boxed warning concerning serious dehydration risk in young children.[1]

FDA-approved indications and claim overlap

FDA indication	Relevant US 8,110,553 claims
Irritable bowel syndrome with constipation in adults	Claims 3, 5, 9 and 10
Chronic idiopathic constipation in adults	Claims 3, 5, 6, 7 and 8
Functional constipation in pediatric patients ages 6 to 17	Broadly related to claims 3, 5 and 6, subject to claim interpretation
Opioid-induced constipation	Claim 7 expressly identifies the condition, but it is not the original core Linzess FDA indication
Postoperative-ileus constipation	Claim 7 expressly identifies the condition

The patent claims are not limited to the exact approved label. They reach several conditions that were not necessarily part of the original approval.

What is the Orange Book status and expiration date of US 8,110,553?

US Patent 8,110,553 has been listed in the FDA Orange Book for Linzess-related protection. The Orange Book identifies patent protection separately from FDA regulatory exclusivity and includes patent-use codes for approved indications.[3]

The ordinary patent expiration date associated with the principal early Linaclotide patent family is December 15, 2025. Any applicable patent-term adjustment, terminal disclaimer, pediatric exclusivity or later Orange Book listing must be assessed against the particular patent and FDA listing record.

Exclusivity timeline

Event	Date or period
Linaclotide patent-family priority activity	Early 2000s
US Patent 8,110,553 issued	February 2012
Linzess approved for adult IBS-C and CIC	August 30, 2012
Pediatric functional-constipation approval	2023
Core early Linzess patent expiration	December 15, 2025
Later formulation and manufacturing protection	Extends beyond the core sequence/use patents

The expiration of US 8,110,553 does not necessarily create unrestricted generic entry. Later-listed patents may cover specific formulations, particle characteristics, manufacturing processes, dosing regimens or other aspects of a generic product.

What patents protect Linzess and linaclotide?

The Linzess patent estate includes several categories of protection:

1. Linaclotide and related peptide compositions.
2. Treatment of constipation and IBS-C.
3. Pharmaceutical formulations.
4. Dosage forms and delivery characteristics.
5. Manufacturing and purification processes.
6. Later-developed pediatric or administration-related uses.

Representative early patents associated with the Linzess franchise include:

Patent	General subject matter	Commercial significance
US 7,304,036	Linaclotide and related GC-C agonist compositions	Core peptide protection
US 8,110,553	Gastrointestinal motility and gastrointestinal-disorder treatment methods	Core method-of-use protection
US 8,748,573	Additional linaclotide treatment methods	Supplemental use protection
US 9,346,884	Later method or use claims	Additional Orange Book protection
US 10,611,828	Later formulation or product-related protection	Potential post-2025 barrier

Patent scope must be evaluated patent by patent. A product can avoid one method-of-use claim while remaining exposed to a composition, formulation or manufacturing claim.

What formulations are protected by the Linzess patent estate?

The principal commercial product is an oral capsule containing linaclotide. Formulation-related patent claims may address:

• Low-dose peptide delivery.
• Stability of the peptide in a solid oral dosage form.
• Excipient systems.
• Moisture control.
• Particle size or peptide distribution.
• Enteric or delayed-release delivery.
• Capsule composition and manufacturing conditions.

US 8,110,553 itself does not recite a capsule, tablet, solution, excipient or enteric coating. It therefore should not be treated as the principal formulation patent. Its direct value lies in the administered peptide and therapeutic use.

How strong is the patent estate for Linzess?

The estate is strongest where a competitor seeks to market the same linaclotide sequence for IBS-C or chronic constipation before the relevant patent barriers expire.

Strength factors

• Claims 2 and 4 identify the exact linaclotide sequence.
• Claims 1 and 3 cover administration for broad therapeutic outcomes.
• Claims 8 and 10 track the two principal commercial uses.
• The product’s FDA-approved indications align closely with the most commercially important claims.
• The peptide is structurally defined, making sequence identity comparatively straightforward to establish.

Weakness factors

• US 8,110,553 is a method patent rather than a composition patent.
• Direct infringement generally requires proof that the patented method is practiced, induced or otherwise legally attributable.
• Generic labeling may omit, carve out or modify patented uses under the FDA’s section viii pathway.
• The broad “effective amount” and “increasing intestinal motility” language may create validity disputes involving written description, enablement, anticipation or obviousness.
• Competitors may challenge the patent through Paragraph IV certification, district-court litigation or administrative proceedings.

The strongest claim chart for a branded Linzess product would map the approved IBS-C and chronic idiopathic constipation indications to claims 8 and 10, while also evaluating independent claims 1 and 3.

Which companies compete with or challenge Linzess?

The commercial competitive set includes both prescription drugs and nonprescription therapies.

Product	Active ingredient	Mechanism or class	Main overlap
Linzess	Linaclotide	GC-C agonist	IBS-C and chronic constipation
Trulance	Plecanatide	GC-C agonist	IBS-C and chronic idiopathic constipation
Amitiza	Lubiprostone	Chloride-channel activator	CIC and IBS-C
Motegrity	Prucalopride	5-HT4 agonist	Chronic constipation
Ibsrela	Tenapanor	NHE3 inhibitor	IBS-C
Relistor and others	Methylnaltrexone or related agents	Peripherally acting opioid antagonists	Opioid-induced constipation

Plecanatide is the closest pharmacologic competitor, but its peptide sequence and patent estate differ from linaclotide’s. A plecanatide product does not inherently practice a claim requiring SEQ ID NO:125.

Generic competition

A generic linaclotide applicant must address the listed patents through one or more certifications:

• Paragraph I: no patent information listed.
• Paragraph II: patent expired.
• Paragraph III: approval deferred until patent expiration.
• Paragraph IV: patent is invalid, unenforceable or will not be infringed.
• Section viii statement: the applicant will not seek approval for a patented method of use.

A Paragraph IV certification can trigger litigation under the Hatch-Waxman Act. A section viii carve-out can reduce exposure to method-of-use patents, but it does not eliminate risk from composition or formulation patents.

What patent litigation affects linaclotide generic entry?

Generic entry risk depends on the full Linzess Orange Book portfolio rather than US 8,110,553 alone. Litigation may involve:

• The core linaclotide composition patent.
• US 8,110,553 method claims.
• Later use patents.
• Formulation patents.
• Patent-term calculations.
• Whether a generic label induces use for IBS-C or chronic constipation.
• Whether a generic formulation practices later product claims.

The principal patent holders and commercial parties associated with Linzess have included Ironwood Pharmaceuticals and Forest Laboratories, later associated with AbbVie after AbbVie’s acquisition of Allergan. Ironwood has retained a major economic interest in the product through its commercialization arrangements.[4]

Public company disclosures have described Paragraph IV challenges and settlements involving generic applicants. Settlement terms can include delayed authorized or licensed generic entry, launch dates, covenants not to sue and restrictions tied to particular patents. Exact entry dates and license rights should be read from the operative settlement documents and current SEC disclosures, not inferred solely from the expiration date of US 8,110,553.[4]

How does US 8,110,553 compare with competing drug patents?

Issue	Linaclotide, US 8,110,553	Plecanatide	Lubiprostone	Prucalopride
Claim type	Method of treatment	Composition and method patents	Small-molecule composition and use patents	Small-molecule composition and use patents
Core mechanism	GC-C agonism	GC-C agonism	Chloride-channel activation	5-HT4 agonism
Sequence-specific exposure	Yes, SEQ ID NO:125	No, different peptide	No	No
IBS-C relevance	Direct, claim 10	Direct	Direct	Less central
Chronic constipation relevance	Direct, claims 7 and 8	Direct	Direct	Direct
Formulation dependence	Relevant to later estate	Relevant	Relevant	Relevant
Biosimilar risk	None in the biologic sense	None in the biologic sense	None	None

Linzess and Trulance are peptide drugs, but neither is a biosimilar product. FDA generic-drug principles, not the biosimilar pathway under the Public Health Service Act, govern abbreviated applications for chemically defined linaclotide products.

What generic launch scenarios exist for linaclotide?

Three scenarios are commercially material.

Scenario 1: Entry after core patent expiration

A generic applicant launches after December 15, 2025, if no later patent or settlement restriction blocks approval. This is the lowest litigation-risk scenario but does not eliminate formulation or manufacturing patent exposure.

Scenario 2: Earlier licensed entry

A settlement may permit entry before the latest asserted patent expiration. The economic result depends on whether entry is authorized, limited by dosage or indication, or subject to a royalty.

Scenario 3: Carved-out-label entry

A generic applicant may omit patented indications from its label. This strategy can reduce induced-infringement exposure under method-of-use patents, but it creates regulatory and commercial limits. If physicians prescribe the generic for the carved-out indication, litigation risk may still depend on the product label, promotional conduct and surrounding facts.

What manufacturing and intellectual-property barriers remain?

Linaclotide is a synthetic peptide with multiple cysteine residues and disulfide bonds. Manufacturing risks include:

• Correct amino-acid sequence.
• Correct disulfide connectivity.
• Control of oxidation and aggregation.
• Purity and impurity characterization.
• Reproducible folding and refolding.
• Stability in the finished dosage form.
• Analytical methods capable of distinguishing relevant variants.

These technical barriers may not independently prevent generic approval, but they increase development and quality-control costs. Later formulation and manufacturing patents can be more important to launch timing than the expired or expiring sequence patent.

What is the revenue exposure from US 8,110,553?

Linzess is a major commercial product for Ironwood and a significant product for its commercial partner. Ironwood reported more than $1 billion in annual Linzess net product sales in recent reporting periods, with US sales accounting for the principal exposure.[4]

The direct revenue risk from US 8,110,553 is concentrated in:

• Adult IBS-C.
• Chronic idiopathic constipation.
• Generic substitution after loss of exclusivity.
• Price erosion following multiple generic launches.
• Any authorized-generic arrangement.
• Channel inventory reductions before generic entry.

A method patent by itself does not determine the date of generic launch. The relevant commercial date is the earliest enforceable entry date under the entire Orange Book and settlement portfolio.

Key Takeaways

• US Patent 8,110,553 covers methods of treating gastrointestinal disorders with linaclotide, identified as SEQ ID NO:125.
• Claims 1 and 3 are broad independent method claims covering intestinal motility and gastrointestinal-disorder treatment.
• Claims 8 and 10 directly cover the principal Linzess uses: chronic constipation and constipation-predominant IBS.
• The patent does not primarily protect a capsule formulation or manufacturing process.
• The core early Linzess patent protection has been associated with an expiration date of December 15, 2025.
• Generic launch depends on the complete Linzess patent estate, including later formulation and use patents.
• Plecanatide, lubiprostone, prucalopride and tenapanor compete commercially but do not practice the linaclotide sequence claim.
• Linaclotide is not a biosimilar product. Generic-drug and Hatch-Waxman rules apply.
• The commercial exposure is substantial because Linzess generates more than $1 billion in annual product sales.

FAQs About US Patent 8,110,553 and Linaclotide

Is US Patent 8,110,553 a composition-of-matter patent?

No. It is principally a method-of-treatment patent. Separate linaclotide composition patents provide different protection.

Does US 8,110,553 cover Trulance?

No. Trulance contains plecanatide, a different peptide. The sequence-specific claim requires linaclotide’s SEQ ID NO:125.

Does the patent cover opioid-induced constipation?

Yes. Claim 7 expressly identifies constipation caused by opiate use.

Can a generic applicant avoid US 8,110,553 by removing IBS-C from its label?

Potentially, through a section viii carve-out, but the generic applicant must also address composition, formulation and other listed patents.

Does expiration of US 8,110,553 guarantee generic Linzess entry?

No. Generic entry can remain blocked or delayed by other Orange Book patents, patent litigation, settlement agreements, regulatory requirements or formulation barriers.

References

1. U.S. Food and Drug Administration. (2024). Linzess (linaclotide) prescribing information.
2. U.S. Food and Drug Administration. (2012, August 30). FDA approves Linzess to treat certain cases of irritable bowel syndrome and constipation.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Ironwood Pharmaceuticals, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934.
5. U.S. Patent and Trademark Office. (2012). US Patent No. 8,110,553, methods and compositions for treating gastrointestinal disorders.
6. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications under the Hatch-Waxman Act.

Drugs Protected by US Patent 8,110,553

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 8,110,553

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1594517		300593	Netherlands
European Patent Office	1594517		C300593	Netherlands
European Patent Office	1594517		CA 2013 00026	Denmark
European Patent Office	1594517		PA2013013	Lithuania