US Patent 10,011,637: Plecanatide Purity, Manufacturing Scope, and Patent Landscape

US Patent No. 10,011,637 protects defined solid-state and impurity characteristics of purified guanylate cyclase-C agonist peptides, including plecanatide, and claims a chromatography, solvent-exchange, and lyophilization process for producing those materials. The patent is materially different from a basic peptide composition patent: its commercial significance depends on whether a competing manufacturer’s plecanatide active pharmaceutical ingredient satisfies every recited purity, density, particle-size, and residual-solvent limitation.

What drug does US Patent 10,011,637 cover?

The patent covers purified GCC agonist peptides. Claim 1 specifically requires the amino acid sequence of SEQ ID NO: 1, which corresponds to plecanatide, the active ingredient in Trulance.

Plecanatide is a 16-amino-acid peptide that activates guanylate cyclase-C receptors in the intestinal epithelium. The FDA approved Trulance for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults. [1]

The patent’s product claims focus on a solid peptide powder with controlled:

Bulk density
Acetamide content
Alpha-Asp-9-plecanatide content
Trifluoroacetic acid content
Stability
Particle-size distribution
Chromatographic purity
Water content
Residual solvents and counterions
Topoisomer and iso-Asp2-plecanatide levels

The process claims extend to a broader group of GCC agonist sequences listed in SEQ ID Nos. 1-54 and 56-251.

What are the key claims of US 10,011,637?

Product claims 1-13

Claim 1 is the principal product claim. A covered peptide must satisfy all four conditions:

Limitation	Threshold
Bulk density	Not greater than 0.1 g/mL
Acetamide	Less than 50 ppm
Alpha-Asp-9-plecanatide	Less than 0.25% by total peptide weight
TFA	Less than 0.05% by total peptide weight

The claim is cumulative. A peptide that meets three limitations but has, for example, 0.08% TFA would not literally satisfy claim 1.

Dependent claims add narrower specifications:

Claim	Added limitation
2	Stability at 25°C for at least three months
3	D10 of about 2-15 μm, D50 of about 15-50 μm, and D90 of about 40-80 μm
4	Bulk density not greater than 0.06 g/mL
5	Chromatographic purity of at least 97%
6	Water content below 10%
7	Less than 0.5% of specified residual impurities
8	Acetonitrile below 300 ppm
9	Isopropanol below 1,000 ppm
10	Isopropanol below 600 ppm
11	Acetate below 0.25%
12	Topoisomers below 2%
13	Iso-Asp2-plecanatide below 2%

Claims 9 and 10 are nested. A product satisfying the 600 ppm isopropanol limitation also satisfies the 1,000 ppm limitation, assuming the other limitations of claim 7 are met.

Process claims 14-24

Claim 14 requires a specific purification sequence:

Providing a peptide solution containing water and acetonitrile.
Loading the solution onto a C18 or polymeric adsorbent column.
Adsorbing the peptide.
Eluting with an aqueous alcohol solution.
Reducing the alcohol content.
Lyophilizing the resulting solution to obtain dry peptide.

The dependent claims narrow the process through:

Isopropanol as the alcohol.
Approximately 40% isopropanol in the elution solution.
Acetamide in the starting solution.
Acetic acid or triethylamine phosphate.
Rotoevaporation.
Reduction of alcohol below 5%.
Redissolution in water.
Addition of ammonium hydroxide or ammonium acetate.
A second lyophilization step.

How strong is the patent scope for plecanatide?

The patent has a specialized but commercially relevant scope. It does not broadly claim every plecanatide molecule. It claims plecanatide in a defined physical and chemical quality state.

Strengths

The product claims combine several independent quality attributes. A competitor would need to avoid at least one limitation to avoid literal infringement. The combination of bulk density, residual acetamide, TFA, and a specific degradation product creates a potentially meaningful barrier where the patented manufacturing process is used to produce the commercial active ingredient.

The process claims also provide a separate infringement route. A manufacturer could avoid a product claim by producing a plecanatide batch with a different impurity profile, but it could still infringe claim 14 if it uses the claimed C18 or polymeric-column purification, alcohol elution, solvent reduction, and lyophilization sequence.

The particle-size limitations in claim 3 may be particularly relevant to powder handling, dose uniformity, dissolution, and downstream formulation. They also create a narrower claim set that may be easier to design around than claim 1.

Limitations

The claims require analytical proof. In an infringement dispute, the patent holder would likely need validated testing for:

Bulk density
Residual acetamide and TFA
Alpha-Asp-9-plecanatide
Particle-size distribution
Water content
Topoisomers and iso-Asp2-plecanatide
Chromatographic purity

The process claims may be difficult to enforce against a foreign manufacturer if the relevant purification steps occur outside the United States. US process-patent remedies are strongest where the claimed process is practiced domestically or where a product made by a patented process is imported under the applicable statutory framework. [2]

When does US Patent 10,011,637 expire?

The patent issued on June 19, 2018. Its effective expiration should be calculated from the earliest claimed nonprovisional priority date, subject to patent-term adjustment, terminal disclaimers, and any patent-term extension.

Public patent records associate the patent with a 2015 priority filing. On that basis, the ordinary twenty-year term would fall in 2035, before any applicable adjustment. The exact enforceable expiration date should be taken from the current USPTO Patent Examination Data System or Patent Center record, not inferred solely from the grant date. [3]

The patent’s expiration is therefore expected to be materially later than the earliest composition patents covering plecanatide. That distinction matters because the patent may continue to affect generic active-ingredient sourcing after earlier composition claims have expired.

What is the Orange Book status of US 10,011,637?

US Patent 10,011,637 is relevant to Trulance because it claims purified plecanatide and manufacturing methods. An Orange Book listing, however, is separate from patent issuance. FDA Orange Book status depends on whether the patent holder submitted the patent for listing and whether FDA accepted it for the relevant approved drug product. [4]

An Orange Book-listed drug patent can support a Paragraph IV certification by an ANDA applicant. A process or active-ingredient patent may create a stronger barrier when the listed patent is tied to the active pharmaceutical ingredient or approved product, but the legal effect depends on the precise listing category and the applicant’s certification.

The patent text alone does not establish:

Whether US 10,011,637 is currently listed against Trulance.
The Orange Book-listed expiration date.
Whether FDA has removed, corrected, or delisted the patent.
Whether the listing is identified as a drug-substance, drug-product, or method-of-use patent.

Those points are regulatory-record questions rather than claim-construction questions.

What Paragraph IV challenges affect plecanatide?

An ANDA applicant seeking to market generic plecanatide would generally address each listed patent through one of four certifications:

Paragraph I: no patent information has been submitted.
Paragraph II: the patent has expired.
Paragraph III: the applicant will wait until expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

For US 10,011,637, likely Paragraph IV strategies would include:

Non-infringement based on impurity levels. The applicant could maintain acetamide, TFA, or alpha-Asp-9-plecanatide above the claimed threshold.
Non-infringement based on density. A bulk density above 0.1 g/mL would avoid claim 1.
Particle-size design-around. A powder could be manufactured outside one or more D10, D50, or D90 ranges.
Alternative purification. A process could use ion exchange, mixed-mode chromatography, preparative HPLC, crystallization, or another adsorbent and avoid claim 14.
Different solvent system. The manufacturer could avoid aqueous isopropanol elution or use a different solvent-reduction method.
Invalidity arguments. Potential grounds would include anticipation, obviousness, lack of written description, enablement, indefiniteness, or claim construction disputes concerning analytical methods.

The strongest design-around opportunity is likely the process claim set. Claim 14 is detailed and requires a particular sequence. A competitor using a materially different purification platform may avoid literal infringement, although the doctrine of equivalents could remain relevant.

What formulation patents protect plecanatide?

US 10,011,637 is principally an active-ingredient quality and manufacturing patent. It does not, on the face of the supplied claims, claim:

A tablet composition.
A coated tablet.
A particular excipient system.
An oral dosage form.
A specific dose.
A treatment regimen.
A pediatric formulation.
A packaging configuration.

Its commercial relevance to formulation is indirect. The claimed powder characteristics can affect blending, flow, content uniformity, dissolution, and stability. A finished dosage form using patented plecanatide API could raise product-patent issues if the API retains the claimed characteristics, but the claims do not automatically cover every finished Trulance tablet.

Method-of-use protection is also absent from the supplied claims. The claims do not recite treating constipation, IBS-C, abdominal pain, or any patient population.

What patent litigation and settlement risks exist?

The claims provided do not identify any litigation, ANDA filer, settlement agreement, or licensing transaction. The patent document itself contains no settlement terms.

For commercial diligence, the relevant litigation questions are:

Issue	Business impact
ANDA Paragraph IV notice	May trigger a 45-day period for filing an infringement action
Litigation filing	Can create a statutory 30-month stay of ANDA approval, subject to statutory exceptions
Claim construction	Determines whether density, impurity, and analytical-method limitations are met
Batch testing	May decide product-claim infringement
Manufacturing discovery	May expose the purification sequence used by a generic
Settlement terms	May establish an agreed generic entry date
License terms	May permit API supply or authorized generic entry

A settlement could allow entry before patent expiration while preserving the patent holder’s commercial position. No such agreement can be inferred from the claims.

Which companies compete around plecanatide?

Plecanatide was developed by Synergy Pharmaceuticals and commercialized in the US under the Trulance brand. Bausch Health acquired Synergy’s assets in 2019 and became associated with Trulance commercialization. [5]

The competitive set includes:

Product	Active ingredient	Category	Competitive relevance
Trulance	Plecanatide	GCC-C agonist	Direct branded reference product
Linzess	Linaclotide	GCC-C agonist	Same constipation and IBS-C market
Amitiza	Lubiprostone	Chloride-channel activator	Alternative prescription mechanism
Motegrity	Prucalopride	5-HT4 agonist	Alternative chronic constipation therapy
OTC products	Multiple ingredients	Laxatives	Price-sensitive substitutes

Plecanatide is a peptide drug, but it is not a biologic requiring a conventional biosimilar pathway. A competing plecanatide product would more commonly proceed through an ANDA or another small-molecule-style abbreviated pathway, depending on FDA’s product-specific regulatory classification. The principal competitive risk is therefore generic or authorized-generic entry, not biosimilar substitution under the Purple Book. [6]

What generic entry risks exist?

Generic entry risk depends on three patent layers:

Earlier plecanatide composition patents.
Later purification and active-ingredient patents such as US 10,011,637.
Any formulation, method-of-use, or regulatory exclusivity protections listed for Trulance.

US 10,011,637 can delay or complicate entry if it is Orange Book-listed and the generic’s API satisfies the product claims or is made using the claimed process. It is less likely to block entry if:

The generic uses a different purification process.
Its API has a different bulk-density profile.
Its residual TFA or acetamide level falls outside the claim.
Its particle-size distribution is outside claim 3.
The patent is not listed against the reference product.
The patent is invalidated or held unenforceable.

The practical risk is highest for an API supplier reproducing the patented purification architecture and targeting the same powder specifications as commercial plecanatide.

How does US 10,011,637 compare with a conventional composition patent?

Attribute	US 10,011,637	Conventional plecanatide composition patent
Primary subject	Purified peptide and manufacturing process	Peptide molecule or sequence
Claim type	Product-by-property and process	Composition of matter
Design-around potential	Relatively high	Usually lower before expiration
Proof of infringement	Requires analytical and process evidence	Often based on chemical identity
Relevance after composition expiry	Potentially significant	Ends with patent expiry
Manufacturing discovery value	High	Often limited
Formulation coverage	Indirect	Usually none unless expressly claimed

Key Takeaways

US 10,011,637 covers purified plecanatide meeting specific density, impurity, stability, particle-size, and moisture specifications.
Claim 1 is cumulative and requires all four principal limitations.
Claims 14-24 cover a defined C18 or polymeric-column purification process followed by alcohol reduction and lyophilization.
The process claims cover multiple GCC agonist sequences, while the principal product claim is directed to SEQ ID NO: 1.
The patent is expected to have an ordinary term extending into approximately 2035, subject to the official USPTO term calculation.
The patent is not a conventional formulation or method-of-use patent.
Generic risk is greatest where the competitor uses the same purification sequence and produces API with the claimed impurity and physical-property profile.
Plecanatide is a peptide drug, but competing products would generally present generic or ANDA risk rather than conventional biosimilar risk.
Current Orange Book listing, Paragraph IV activity, litigation, and settlement status must be determined from the live FDA and court records rather than the patent claims.

FAQs

Can a generic plecanatide avoid US 10,011,637 by changing only particle size?

Potentially. Changing particle size could avoid claim 3, but it would not avoid claim 1 unless the change also alters a required claim 1 limitation, such as bulk density or one of the specified impurity levels.

Does claim 1 cover plecanatide in a finished Trulance tablet?

Not automatically. Claim 1 is directed to a purified peptide with specified properties. A finished tablet could infringe if the claimed peptide is present and the claim is otherwise met, but the claim does not expressly recite the tablet, excipients, coating, or dosage form.

Can a manufacturer use a different alcohol and avoid the process claims?

Possibly. Claim 14 requires elution with an alcohol aqueous solution, while dependent claims specify isopropanol. A different alcohol may avoid the narrower isopropanol claims, but it may still fall within claim 14 depending on claim construction.

Is US 10,011,637 a biosimilar patent?

No. The patent claims a purified GCC agonist peptide and its manufacture. Plecanatide competition is generally analyzed through generic-drug and ANDA principles, not through the standard monoclonal-antibody biosimilar framework.

What evidence would be most important in a Paragraph IV dispute?

The most important evidence would include the generic API specification, batch analytical data, particle-size testing, bulk-density measurements, impurity chromatograms, residual-solvent results, manufacturing batch records, and chromatography and lyophilization procedures.

References

U.S. Food and Drug Administration. (2017). Trulance (plecanatide) prescribing information.
United States Code, 35 U.S.C. §§ 271, 295.
United States Patent and Trademark Office. (2018). U.S. Patent No. 10,011,637, Purified guanylate cyclase C agonist peptides.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations, Orange Book.
Bausch Health Companies Inc. (2019). Bausch Health completes acquisition of Synergy Pharmaceuticals’ assets.
U.S. Food and Drug Administration. (2025). Purple Book: Database of licensed biological products.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Salix	TRULANCE	plecanatide	TABLET;ORAL	208745-001	Jan 19, 2017		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial		Y			⤷ 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	2014274812	⤷ Start Trial
Australia	2018226473	⤷ Start Trial
Australia	2020205349	⤷ Start Trial
Brazil	112015030326	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,011,637

Which drugs does patent 10,011,637 protect, and when does it expire?

Summary for Patent: 10,011,637