United States Patent 10,307,417: Claim Scope, Expiration, Orange Book Status, and Methylnaltrexone Patent Landscape

U.S. Patent No. 10,307,417 protects a narrow oral methylnaltrexone bromide tablet platform that uses sodium dodecyl sulfate, also called sodium lauryl sulfate, to create an ion pair and improve dissolution and apparent lipophilicity in acidic conditions. The strongest commercial claims target a non-enteric-coated tablet containing methylnaltrexone bromide and SDS at approximately a 3:1 weight ratio, including a 150 mg/50 mg dose configuration. The patent does not broadly cover methylnaltrexone, all oral formulations, injectable products, or methods of treating opioid-induced constipation.

The patent issued June 4, 2019. Based on its ordinary 20-year term calculated from its earliest nonprovisional priority date, the expected expiration is in 2032, subject to any applicable patent-term adjustment or other term modification.[1]

What does U.S. Patent 10,307,417 protect?

The patent protects a pharmaceutical composition for oral administration with five central limitations:

Methylnaltrexone bromide is the sole active agent.
Sodium dodecyl sulfate is present.
The product is a tablet.
The tablet is not enterically coated.
At least 50% of the composition dissolves within approximately 15 minutes under the specified acidic paddle dissolution test.

The independent claim is composition-based. It does not require a particular therapeutic indication, dosing schedule, manufacturing process, tablet weight, or commercial brand.

Claim element	Scope
Active ingredient	Methylnaltrexone bromide
Other active agents	Excluded; methylnaltrexone must be the sole active agent
Surfactant	Sodium dodecyl sulfate
Dosage form	Tablet
Route	Oral administration
Coating	No enteric coating
Dissolution medium	900 mL of 0.1 N HCl
Apparatus	Paddle apparatus at 100 rpm
Temperature	37°C
Minimum dissolution in claim 1	At least 50% within about 15 minutes
Preferred dissolution	At least 75% or 90% within about 15 minutes
Preferred ratio	Approximately 3:1 methylnaltrexone bromide:SDS
Preferred dose	150 mg methylnaltrexone bromide and 50 mg SDS
Additional excipients	Rapid-acting disintegrants and chelating agents are covered in dependent claims

Because claim 1 uses the transition “comprising,” the claim permits additional inactive ingredients unless another limitation excludes them. The “sole active agent” limitation prevents a combination product with another pharmacologically active ingredient from satisfying the claim.

How do the dependent claims narrow the patent?

The dependent claims create several overlapping fallback positions. A product need not satisfy every dependent limitation to infringe claim 1, but the dependent claims can provide narrower infringement theories and potentially stronger validity positions.

Dissolution limitations

Claims 5 and 6 require at least 75% and 90% dissolution, respectively, within approximately 15 minutes. Claims 15 and 16 apply the same thresholds to the approximately 3:1 formulation.

These limitations are technically important because they create a measurable performance boundary. A competing tablet with the same ingredients but slower dissolution could avoid the narrower claims while still potentially falling within claim 1 if it reaches at least 50% dissolution.

The phrase “about 15 minutes” introduces ordinary claim-construction questions concerning experimental variability, acceptable analytical tolerances, and the meaning of “about” in the specification. The test conditions are unusually specific, which may limit the relevance of results generated under a different medium, apparatus, agitation speed, volume, or temperature.

Ion-pair limitations

Claims 7 through 10 and 17 through 18 require formation of an ion pair when methylnaltrexone bromide and SDS are dissolved in solution. The relevant pH range is approximately 1 to 4.

These claims are directed to a functional chemical interaction rather than merely the co-presence of the ingredients. A formulation containing SDS may not satisfy these claims if the required ion pair does not form under the claimed conditions. Conversely, a defendant may face analytical discovery concerning the formulation’s behavior in acidic solution.

Partition-coefficient limitations

Claims 11 through 13 require an apparent octanol/water partition coefficient for methylnaltrexone of at least 0.25, 0.5, or 1 at a pH between 1 and 4.

The partition-coefficient claims attempt to capture the effect of SDS on methylnaltrexone’s distribution between aqueous and organic phases. They may be relevant to formulation designs using alternative ratios or excipient levels, provided the product satisfies the other limitations of claim 1.

The term “apparent” is significant. The measurement concerns the formulation’s observed distribution behavior under specified acidic conditions, rather than necessarily the intrinsic partition coefficient of unformulated methylnaltrexone.

Disintegrant limitations

Claims 2 through 4 require a rapid-acting disintegrant, including an effervescent disintegrant or sodium bicarbonate. These claims address rapid tablet breakup and may support the dissolution limitations.

A tablet using crospovidone, croscarmellose sodium, sodium starch glycolate, sodium bicarbonate, or another fast-disintegrating system could raise different infringement questions depending on whether the excipient satisfies the claim language and the patent’s construction of “rapid-acting.”

Chelating-agent limitations

Claims 20 through 23 add a chelating agent. Claim 21 specifically identifies calcium EDTA disodium.

These claims could cover a formulation designed to control metal-ion interactions or improve stability. The chelating-agent limitations are narrower than claim 1 and do not appear necessary for coverage of a basic methylnaltrexone/SDS tablet.

What formulations are protected by U.S. Patent 10,307,417?

The principal commercial formulation target is a tablet containing 150 mg methylnaltrexone bromide and 50 mg SDS. Claims 24 through 29 expressly identify that configuration and connect it to the 3:1 ratio, dissolution, and ion-pair limitations.

Formulation type	Claim relevance
150 mg methylnaltrexone bromide/50 mg SDS tablet	Directly targeted by claims 25, 27, and 29
Approximately 3:1 methylnaltrexone bromide:SDS tablet	Claims 14-19
Tablet with rapid-acting disintegrant	Claims 2-4
Tablet with sodium bicarbonate	Claim 4
Tablet with chelating agent	Claims 20-23
Tablet meeting at least 75% dissolution	Claims 5 and 15
Tablet meeting at least 90% dissolution	Claims 6 and 16
Enteric-coated tablet	Outside claim 1 as written
Capsule, liquid, or injectable formulation	Outside the express dosage-form limitation of claim 1
Combination tablet with another active agent	Outside the “sole active agent” limitation

The claims are formulation-specific, not molecule-wide. An oral methylnaltrexone product using a different dosage form, a different surfactant, or a non-SDS absorption strategy may avoid literal infringement, although the doctrine of equivalents could become relevant in litigation.

How strong is the patent estate for methylnaltrexone?

U.S. Patent 10,307,417 appears strongest against a direct copy of the claimed oral tablet architecture. Its commercial significance depends on whether the marketed product contains SDS at the claimed level and satisfies the dissolution and, where asserted, ion-pair limitations.

Its strengths are:

A concrete combination of active ingredient and excipient.
Multiple quantitative dissolution thresholds.
A specified 3:1 ratio.
Dose-specific claims covering 150 mg methylnaltrexone bromide and 50 mg SDS.
Functional claims directed to ion pairing and partition behavior.
Coverage of rapid-disintegrant and chelating-agent variants.

Its limitations are:

No broad claim to methylnaltrexone bromide itself.
No claim to all oral dosage forms.
No method-of-use claim for opioid-induced constipation.
No claim to injectable methylnaltrexone.
No express protection for a different surfactant.
Dependence on potentially contestable laboratory results.
Possible design-around options involving non-tablet dosage forms, alternate excipients, alternate ratios, or slower dissolution.

The patent’s validity could be tested against prior art involving oral quaternary ammonium opioid antagonists, surfactant-mediated ion pairing, pharmaceutical dissolution enhancement, and methylnaltrexone formulations. The most vulnerable issues would likely include written description and enablement across the breadth of the functional limitations, obviousness of combining methylnaltrexone with SDS, and the reproducibility of the claimed dissolution and partition-coefficient results.

When does U.S. Patent 10,307,417 lose exclusivity?

The patent issued in 2019 and is expected to expire in 2032 under the ordinary patent-term framework.[1] The exact terminal date depends on the patent’s recorded term adjustment and any applicable term extension.

Event	Date or status
Patent issued	June 4, 2019
Patent number	U.S. 10,307,417
Expected ordinary term end	Approximately 2032
Patent-term adjustment	Must be confirmed from the USPTO patent record
Regulatory exclusivity	Separate from patent term
Generic entry	Could occur before patent expiration through a successful Paragraph IV challenge or authorized arrangement

Patent expiration does not automatically determine generic entry. A generic applicant may challenge the patent, settle with the patent holder, or obtain a license for an earlier launch. Conversely, a patent may remain enforceable after regulatory exclusivity ends.

What is the FDA and Orange Book status of the methylnaltrexone product?

Relistor, marketed by RedHill Biopharma after its acquisition of rights from Bausch Health-related entities, is the principal U.S. methylnaltrexone product. FDA-approved products include oral tablets and subcutaneous injection products for opioid-induced constipation in specified patient populations.[2]

Methylnaltrexone is a small-molecule drug. It is therefore subject to the ANDA pathway and Paragraph IV patent certification framework, not the biosimilar pathway under the Public Health Service Act.[3]

The Orange Book analysis should distinguish:

Listed patents covering the approved drug product.
Patents covering methods of use.
Formulation patents issued after initial approval.
Regulatory exclusivity periods.
Whether a particular patent has been submitted for listing and remains listed.

An Orange Book listing does not establish validity or infringement. It affects FDA approval timing and the statutory notice-and-stay framework for an ANDA applicant.

The relevant FDA regulatory milestones include approval of oral Relistor tablets for opioid-induced constipation and separate approval of the injectable product. The oral tablet’s approved dose is administered as methylnaltrexone bromide tablets, with the labeled regimen differing by indication and patient population.[2]

What generic entry risks exist for Relistor?

A generic applicant targeting the oral product would likely evaluate at least four design strategies.

Direct formulation challenge

The applicant could copy the active ingredient, tablet form, SDS, dose, and dissolution profile, then file a Paragraph IV certification against listed patents. This creates the highest infringement exposure but may produce the closest bioequivalence profile.

Excipient substitution

The applicant could use a different surfactant or a different disintegration system. This approach may avoid claims expressly requiring SDS, but it must still satisfy bioequivalence and product-quality requirements.

Ratio modification

A formulation outside the approximately 3:1 methylnaltrexone bromide:SDS ratio could avoid the narrower claims. It may remain exposed to claim 1 if it contains SDS, is a non-enteric-coated tablet, and meets the 50% dissolution threshold.

Dosage-form redesign

A capsule, multiparticulate system, liquid, or alternative delivery system could avoid the tablet limitation. The commercial and regulatory burden would be higher if the redesign changes dissolution, absorption, or pharmacokinetic behavior.

The principal competitive risk is therefore formulation-specific rather than molecule-wide. A challenger that avoids SDS and the tablet limitation may have a stronger noninfringement position but could face a more difficult development program.

Which companies are challenging the methylnaltrexone patent estate?

Publicly available patent information does not establish a definitive Paragraph IV challenger or a final settlement involving U.S. Patent 10,307,417. The patent itself is not evidence of litigation activity, and FDA Orange Book listing data must be matched with court dockets to determine whether an ANDA challenge has occurred.

For diligence purposes, the relevant litigation questions are:

Whether U.S. Patent 10,307,417 is listed for the approved oral methylnaltrexone product.
Whether an ANDA applicant has served a Paragraph IV notice.
Whether the patent holder filed an infringement action within the 45-day statutory period.
Whether a 30-month stay was triggered.
Whether the parties executed a launch-date settlement.
Whether any authorized generic or license was included in the settlement.

Absent a verified docket or FDA notice, no challenger, settlement date, or agreed launch date should be treated as established.

Does the patent cover biosimilars or injectable methylnaltrexone?

No. Biosimilar risk is not the relevant framework because methylnaltrexone bromide is a small molecule. The patent also does not expressly cover injectable methylnaltrexone because the claims require a tablet for oral administration.

An injectable product would fall outside the literal scope of claim 1 even if it contained methylnaltrexone bromide and SDS. The patent likewise does not cover a general method of treating opioid-induced constipation.

How does this patent compare with broader methylnaltrexone patents?

Patent category	Typical protected subject matter	Relevance to U.S. 10,307,417
Core compound patents	Methylnaltrexone or related opioid antagonists	Broader molecule protection, but generally older
Salt or crystalline-form patents	Bromide salts, polymorphs, solid-state forms	May cover the API independently of the tablet
Method-of-use patents	Opioid-induced constipation and related indications	Can delay approved-use generic marketing
Injectable formulation patents	Subcutaneous or parenteral products	Separate from the claimed tablet
Oral formulation patents	Surfactant, dissolution, absorption, and tablet systems	Closest category to U.S. 10,307,417
Manufacturing patents	Synthesis, purification, crystallization, or processing	Can create supply-chain barriers
U.S. 10,307,417	Methylnaltrexone/SDS non-enteric tablet	Narrow but commercially targeted

The patent should therefore be analyzed as one layer of a possible estate. Freedom-to-operate analysis requires separate review of compound, salt, formulation, manufacturing, and method-of-use patents, as well as terminal disclaimers and patent-family continuations.

What manufacturing and geographic barriers exist?

The patent’s geographic scope is limited to the United States. Foreign counterparts may have different claim sets, prosecution histories, expiration dates, and validity outcomes. A global launch requires separate analysis in Europe, Canada, Japan, China, Australia, and other target markets.

Manufacturing risks include:

Maintaining the claimed SDS-to-methylnaltrexone ratio.
Controlling tablet disintegration and dissolution.
Demonstrating batch-to-batch compliance with the acidic dissolution method.
Managing surfactant distribution during blending and compression.
Preventing stability problems involving excipients or metal ions.
Determining whether calcium EDTA disodium is necessary or commercially practical.

A process that produces the same final composition can still implicate the composition claims even if the manufacturing method differs. Conversely, a manufacturing patent could create exposure even when the final tablet avoids U.S. Patent 10,307,417.

Key Takeaways

U.S. Patent 10,307,417 is a narrow oral formulation patent, not a broad methylnaltrexone patent.
Claim 1 requires a non-enteric-coated tablet containing methylnaltrexone bromide and SDS, with methylnaltrexone as the sole active agent.
The key commercial embodiment is approximately 150 mg methylnaltrexone bromide and 50 mg SDS.
Dependent claims add rapid disintegrants, sodium bicarbonate, chelating agents, ion pairing, partition coefficients, and faster dissolution.
The patent does not literally cover injectable products, capsules, liquids, biosimilars, or combination products with another active agent.
The expected ordinary expiration is approximately 2032, subject to recorded patent-term adjustment.
Generic risk is highest for an ANDA product that copies the SDS-based tablet architecture.
Alternative surfactants, dosage forms, ratios, or dissolution profiles may provide design-around opportunities.
Paragraph IV activity, Orange Book listing, litigation, and settlement status must be established from FDA records and court dockets rather than inferred from the patent claims.
A complete freedom-to-operate review must include the broader methylnaltrexone compound, salt, method-of-use, injectable, manufacturing, and foreign patent estates.

Frequently Asked Questions

Does U.S. Patent 10,307,417 cover Relistor itself?

It may cover an oral Relistor tablet if the marketed product contains the claimed SDS component, satisfies the tablet and coating limitations, and meets the relevant dissolution requirements. The patent does not automatically cover every Relistor presentation.

Can a generic avoid the patent by using sodium lauryl sulfate instead of SDS?

Sodium lauryl sulfate is a common name for sodium dodecyl sulfate. Changing that label alone would not avoid the SDS limitation.

Does a 450 mg methylnaltrexone dose fall within the 150 mg claims?

A 450 mg dose does not satisfy a claim requiring approximately 150 mg in a single tablet. It could still implicate broader claims if the product otherwise satisfies claim 1 or another asserted claim.

Is a tablet with 49% dissolution at 15 minutes outside the patent?

It would not satisfy the literal 50% dissolution threshold of claim 1 based solely on that result. The test conditions, analytical variability, and construction of “about 15 minutes” would remain relevant in an infringement dispute.

Can a formulation with SDS but no sodium bicarbonate infringe?

Yes. Sodium bicarbonate is required only by dependent claim 4. A tablet without sodium bicarbonate may still fall within claim 1 or other dependent claims if all applicable limitations are met.

References

United States Patent and Trademark Office. (2019). U.S. Patent No. 10,307,417, pharmaceutical composition claims for oral methylnaltrexone bromide formulations.
U.S. Food and Drug Administration. (n.d.). Relistor (methylnaltrexone bromide) prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions and Paragraph IV patent certifications.
U.S. Food and Drug Administration. (n.d.). Purple Book: Lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations.

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	RELISTOR	methylnaltrexone bromide	TABLET;ORAL	208271-001	Jul 19, 2016		RX	Yes	Yes	10,307,417	⤷ 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
Argentina	080491	⤷ Start Trial
Australia	2011224275	⤷ Start Trial
Brazil	112012022873	⤷ Start Trial
Canada	2789798	⤷ Start Trial
Chile	2012002192	⤷ Start Trial
China	102918039	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,307,417

Which drugs does patent 10,307,417 protect, and when does it expire?

Summary for Patent: 10,307,417