Details for Patent: 10,058,536

Which drugs does patent 10,058,536 protect, and when does it expire?

Patent 10,058,536 protects MYRBETRIQ GRANULES and is included in one NDA.

Protection for MYRBETRIQ GRANULES has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has thirteen patent family members in thirteen countries.

Summary for Patent: 10,058,536

Title:	Pharmaceutical composition containing mirabegron
Abstract:	To provide: (1) a modified release liquid (suspension) containing mirabegron, (2) a ready-to-suspend pharmaceutical composition containing mirabegron, and (3) a mirabegron-containing pharmaceutical composition that does not generate undissolved lumps, even when it is suspended at the time of use. The present invention relates to a pharmaceutical composition containing a complex of mirabegron or a pharmaceutically acceptable salt thereof with sodium polystyrene sulfonate.
Inventor(s):	Seiji Takae, Toshiro Sakai, Yuki Kasashima, Yurina Ansei, Tsuyoshi Kiyota
Assignee:	Astellas Pharma Inc
Application Number:	US15/553,107
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 10,058,536: Mirabegron Suspension Composition Claims, Patent Scope and Generic-Entry Risk

US Patent No. 10,058,536 protects a specific oral mirabegron formulation that uses sodium polystyrene sulfonate, a thickener, and magnesium stearate and/or calcium stearate. The patent is directed primarily to ready-to-suspend or otherwise release-modified formulations, not to mirabegron as an active pharmaceutical ingredient.

The commercial risk is concentrated in liquid or reconstitutable mirabegron products that reproduce the claimed excipient architecture. A conventional mirabegron extended-release tablet would not infringe claim 1 merely because it contains mirabegron.

What does US Patent 10,058,536 claim?

The independent claims establish two different protection categories:

Claim	Claim type	Core protected subject matter
1	Composition	Mirabegron or salt complexed with sodium polystyrene sulfonate, a thickener, and magnesium stearate and/or calcium stearate
9	Method	Administering the same type of composition to modify mirabegron release

Claim 1 is the principal composition claim. It requires every listed component. The claim does not expressly require a particular dose, particle size, release profile, disease indication, or administration route.

Claim 9 is broader in one respect because it is not expressly limited to a particular indication. It is narrower in another respect because it requires administration and a purpose of modifying mirabegron release.

The claim set is therefore formulation-specific rather than molecule-specific.

What is the technical purpose of the patented formulation?

Mirabegron is a beta-3 adrenergic receptor agonist used for overactive bladder. Sodium polystyrene sulfonate is an ion-exchange resin capable of forming a complex with a basic drug. In this formulation, the complex can moderate drug release by controlling the availability of mirabegron in the gastrointestinal environment.

The thickener contributes suspension stability and rheological control. Xanthan gum is the preferred thickener identified in the claims. Magnesium stearate and calcium stearate are hydrophobic excipients that can modify wetting, dispersion, and release from the resin-drug complex.

The combination is technically important because the claims require the resin complex, thickener, and hydrophobic substance together. Omitting any one of those elements generally removes a composition from the literal scope of claim 1.

Claim-element map

Required element	Claim 1 status	Practical significance
Mirabegron or pharmaceutically acceptable salt	Required	A different active ingredient is outside the claim
Complex with sodium polystyrene sulfonate	Required	Mere physical mixing may not satisfy the complex limitation
Thickener	Required	The formulation must contain a qualifying thickening agent
Magnesium stearate and/or calcium stearate	Required	Other hydrophobic excipients alone do not literally satisfy this limitation
Hydrophobic substance content of 0.5% to 35% relative to thickener	Claim 2 only	A product outside this ratio may avoid claim 2 but remain within claim 1
Listed thickener	Claim 3	Dependent narrowing limitation
Xanthan gum	Claim 4	Narrowest expressly preferred thickener claim
Thickener at 1% to 70% of composition weight	Claim 5	Adds a broad quantitative limitation
Ready-to-suspend composition	Claim 6	Relevant to dry suspensions and reconstitutable products
Oral administration	Claim 7	Narrows the claim to oral dosage products
Overactive-bladder treatment	Claim 8	Narrows the therapeutic use
Administration to modify release	Claim 9	Creates method-of-use infringement exposure

How broad is claim 1 of US 10,058,536?

Claim 1 is chemically and functionally constrained but commercially meaningful. It does not require xanthan gum, a ready-to-suspend product, oral administration, or an overactive-bladder indication. Those features appear in dependent claims 4, 6, 7, and 8.

A formulation can therefore fall within claim 1 if it uses a different thickener, provided the thickener is not excluded by claim construction and the formulation still contains the required resin complex and stearate.

The critical limitation is the phrase "a complex of mirabegron ... with sodium polystyrene sulfonate." A product developer could contest infringement by arguing that:

1. Mirabegron is not complexed with sodium polystyrene sulfonate.
2. The resin is present only as an inactive excipient.
3. The product uses a different ion-exchange resin.
4. The product uses a different stearate or hydrophobic excipient.
5. The formulation lacks a qualifying thickener.

The first issue is likely to be the most technically significant. Analytical evidence concerning drug loading, ion exchange, dissolution, resin binding, and release behavior would be relevant to infringement and validity disputes.

What formulations are protected by claims 2 through 8?

Hydrophobic-substance ratio

Claim 2 covers a hydrophobic-substance-to-thickener ratio of 0.5% to 35% by weight, calculated relative to the weight of the thickener.

The ratio is not calculated against the total composition weight. A product with 10% xanthan gum and 1% magnesium stearate would have a hydrophobic-substance-to-thickener ratio of 10%, assuming the percentages are measured on the same weight basis.

The dependent ratio claim creates a potential design-around route. A formulation outside the 0.5% to 35% range may avoid claim 2, although claim 1 would remain relevant.

Covered thickeners

Claim 3 lists the following alternatives:

• Xanthan gum
• Guar gum
• Locust bean gum
• Gellan gum
• Sodium carboxymethyl cellulose
• Gelatin
• Hydroxyethyl cellulose
• Hydroxypropyl cellulose
• Carrageenan
• Methylcellulose
• Sodium alginate
• Hypromellose
• Polyvinyl alcohol

Claim 3 is drafted as a Markush limitation. It narrows the thickener to one or more members of the listed group. Claim 4 narrows that group to xanthan gum.

The presence of xanthan gum is commercially relevant because it is a common suspension stabilizer and is specifically singled out in the claims.

Thickener concentration

Claim 5 requires the thickener to represent 1% to 70% by weight of the pharmaceutical composition. The upper end is unusually broad for many conventional oral dosage forms but may be relevant to dry, ready-to-suspend compositions.

A product below 1% or above 70% may avoid claim 5 while remaining exposed to claim 1 or another dependent claim.

Ready-to-suspend and oral products

Claim 6 covers a ready-to-suspend pharmaceutical composition. This language is relevant to powders or granules that are reconstituted before administration, as well as other dosage forms designed to produce a suspension.

Claim 7 expressly limits the product to oral administration. Claim 1 itself does not include that limitation. An oral product therefore can implicate both the broad composition claim and the narrower oral-use claim.

Overactive-bladder treatment

Claim 8 identifies:

• Urinary urgency
• Urinary frequency
• Urge urinary incontinence
• Neuropathic detrusor overactivity

The claim ties these conditions to overactive bladder. A product labeled for one of those indications could create additional method-of-use exposure if the formulation meets the composition limitations.

What is the likely patent term and expiration date?

US Patent No. 10,058,536 was granted on August 28, 2018. Its enforceable term is generally calculated from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, terminal disclaimers, patent-term extension, and other statutory adjustments.[1]

Public patent records identify the patent as an Astellas-related mirabegron formulation patent. The effective expiration should be confirmed from the USPTO patent file and the patent-term data because the grant date alone does not determine expiration.

A conventional 20-year calculation from an international or US filing date in the mid-2010s would place expiration in the mid-2030s. The operative expiration date may differ because of:

• Patent-term adjustment
• Earlier priority claims
• Continuation or divisional relationships
• Terminal disclaimers
• Patent-term extension
• Any disclaimer or correction recorded by the USPTO

Event	Date or status
Patent grant	August 28, 2018
US patent number	10,058,536
Principal subject	Mirabegron-resin suspension and release-modifying composition
Likely assignee group	Astellas-related
Ordinary term basis	20 years from applicable earliest nonprovisional filing
Confirmed expiration	Requires USPTO term calculation and family-file review

Is US 10,058,536 listed in the FDA Orange Book?

The patent text alone does not establish Orange Book listing. Orange Book listing depends on whether the patent was submitted for an approved drug product and accepted by FDA under the applicable listing rules.[2]

The approved US mirabegron product, Myrbetri, is an extended-release tablet marketed by Astellas. The claims of US 10,058,536 are directed to a resin complex, thickener, and stearate-containing composition, with ready-to-suspend embodiments in the dependent claims. That subject matter is materially different from a conventional extended-release tablet.

This distinction creates three possible regulatory positions:

Scenario	Generic consequence
Patent is not listed for the relevant mirabegron NDA	An ANDA applicant generally has no Orange Book Paragraph IV certification obligation for this patent
Patent is listed for the relevant NDA	An ANDA applicant may need a certification under 21 U.S.C. § 355(j)(2)(A)(vii)
Patent covers an approved product or use but not the proposed generic product	The applicant may use a Paragraph III, Paragraph IV, or section viii strategy depending on the listing and proposed labeling

A Paragraph IV challenge matters only if the patent is listed against the reference drug and the proposed ANDA product falls within the relevant patent listing. A patent can create ordinary infringement risk under 35 U.S.C. § 271 without necessarily creating an Orange Book stay risk.[3]

Does the patent create biosimilar risk?

No meaningful biosimilar risk applies. Mirabegron is a small-molecule drug, not a biologic subject to the Biologics Price Competition and Innovation Act pathway.

Competitive entry would normally occur through the ANDA pathway for a generic drug, not through a biosimilar application under section 351(k) of the Public Health Service Act.

The relevant competitive questions are:

• Whether the generic product is an extended-release tablet or a suspension.
• Whether it contains a sodium polystyrene sulfonate complex.
• Whether it uses magnesium stearate or calcium stearate.
• Whether the patent is listed in the Orange Book.
• Whether an ANDA applicant makes a Paragraph IV certification.
• Whether the applicant launches at risk after the 30-month stay or after litigation resolution.

What generic launch scenarios exist?

Conventional extended-release tablet

A conventional mirabegron extended-release tablet that lacks sodium polystyrene sulfonate, a qualifying thickener, and magnesium or calcium stearate should have a strong noninfringement position against claim 1.

The patent would be less relevant to the ordinary tablet market unless the tablet uses the claimed complex and excipient combination.

Reconstitutable oral suspension

A reconstitutable suspension using mirabegron, sodium polystyrene sulfonate, xanthan gum, and magnesium stearate would present the highest infringement risk. It could potentially meet claims 1, 4, 6, and 7, and possibly claim 2 or claim 5 depending on the formulation ratios.

Liquid suspension prepared by a pharmacist

A liquid product prepared from a powder or granule could implicate claim 6 if it is a ready-to-suspend composition. The final dosage form and manufacturing process would need separate analysis.

Alternative resin formulation

Replacing sodium polystyrene sulfonate with another ion-exchange resin would provide a direct design-around position against the express claim language. The patent holder could still assert equivalents, but the technical and legal case would depend on the identity of the resin, the function it performs, and the prosecution history.

Alternative hydrophobic excipient

Replacing magnesium stearate and calcium stearate with another hydrophobic substance would avoid the literal limitation if the substitute is not legally treated as one of the claimed stearates. The risk of a doctrine-of-equivalents claim would depend on whether the substitute performs substantially the same function in substantially the same way to produce substantially the same result.

How strong is the patent estate?

The patent has moderate formulation protection and limited platform protection.

Strength factor	Assessment
Active ingredient coverage	Weak; it does not claim mirabegron generally
Broad formulation coverage	Moderate; claim 1 covers the required four-part combination
Preferred-formulation coverage	Stronger; xanthan gum and ready-to-suspend embodiments are expressly claimed
Design-around difficulty	Moderate; resin, hydrophobic excipient, and thickener can potentially be changed
Tablet-market relevance	Limited unless the tablet uses the claimed resin complex
Suspension-market relevance	High
Method-of-use coverage	Moderate; claim 9 requires administration and release modification
Biosimilar relevance	None
Orange Book impact	Dependent on listing against an approved NDA

The estate's commercial value is highest if the patented formulation is necessary for a commercially viable liquid or ready-to-suspend mirabegron product. Its value is lower if the market is limited to Myrbetri-type extended-release tablets or if equivalent release control can be achieved with a different resin and excipient system.

What patent litigation or licensing issues should be reviewed?

The patent number and claims do not establish a litigation history, settlement agreement, or license. Those issues require review of:

• USPTO assignment and maintenance records
• PACER and district-court dockets
• FDA Orange Book patent listings
• ANDA litigation complaints
• Astellas licensing and collaboration disclosures
• SEC filings and annual reports
• Patent family members in Japan, Europe, and other commercial jurisdictions

A license covering the underlying mirabegron compound or Myrbetri tablet would not necessarily authorize use of the claimed sodium-polystyrene-sulfonate suspension formulation. Formulation rights must be analyzed separately from active-ingredient rights.

What geographic coverage exists outside the United States?

US Patent 10,058,536 provides rights only in the United States. Foreign protection must be assessed through its patent family. A PCT publication, if applicable, would not itself create enforceable rights in every designated country. National-stage patents must be separately verified.

The most commercially relevant jurisdictions are likely to include:

• Japan
• European Patent Convention states
• Canada
• Australia
• South Korea
• China

Foreign claim scope may differ materially because of national prosecution amendments, unity objections, added-matter standards, claim-support requirements, and local patent-term rules.

Key Takeaways

• US 10,058,536 protects a mirabegron composition containing a sodium polystyrene sulfonate complex, a thickener, and magnesium stearate and/or calcium stearate.
• The patent does not broadly cover mirabegron, Myrbetri, or every mirabegron extended-release tablet.
• The highest-risk products are ready-to-suspend or oral suspension formulations using xanthan gum and one of the claimed stearates.
• Claim 2 covers a hydrophobic-substance-to-thickener ratio of 0.5% to 35%.
• Claim 9 creates method-of-use exposure for administration intended to modify mirabegron release.
• Biosimilar risk is not relevant because mirabegron is a small molecule.
• Paragraph IV exposure depends on whether the patent is listed for the relevant FDA-approved reference product.
• A conventional tablet that lacks the claimed resin complex and thickener combination has a stronger noninfringement position.
• The principal design-around options are changing the ion-exchange resin, replacing the claimed stearate, or eliminating the claimed thickener architecture.
• The operative patent expiration date requires confirmation from USPTO term-adjustment and family records.

FAQs

Does US Patent 10,058,536 cover Myrbetri tablets?

Not automatically. The claims require a sodium polystyrene sulfonate complex, a thickener, and magnesium stearate and/or calcium stearate. A conventional mirabegron extended-release tablet lacking that combination would not literally meet claim 1.

Can a generic avoid the patent by using a different ion-exchange resin?

A different resin may provide a literal noninfringement position because the claims expressly require sodium polystyrene sulfonate. The patent holder could still evaluate an equivalents theory, depending on the technical function and prosecution history.

Does using xanthan gum create infringement by itself?

No. Xanthan gum alone is not enough. Infringement requires the other claim elements, including the mirabegron-sodium-polystyrene-sulfonate complex and magnesium stearate and/or calcium stearate.

Is a Paragraph IV certification required for every generic mirabegron product?

No. Paragraph IV certification obligations depend on the patents listed for the relevant reference drug and the scope of the proposed generic product. An unlisted formulation patent does not automatically create a Paragraph IV certification requirement.

Can the patent block a compounded mirabegron suspension?

Potentially, if the compounded product and manufacturing activity satisfy the claim limitations. The analysis would depend on the composition, preparation method, use, statutory exemptions, and whether the activity is commercial or clinical.

References

1. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-adjustment
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
3. U.S. Code, 21 U.S.C. § 355(j). (2024). Abbreviated applications for new drugs. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section355
4. U.S. Code, 35 U.S.C. § 271. (2024). Infringement of patent. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section271
5. U.S. Patent No. 10,058,536. (2018). Pharmaceutical composition. United States Patent and Trademark Office.

Drugs Protected by US Patent 10,058,536

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Apgdi	MYRBETRIQ GRANULES	mirabegron	FOR SUSPENSION, EXTENDED RELEASE;ORAL	213801-001	Mar 25, 2021	AB	RX	Yes	Yes	10,058,536*PED				Y

Foreign Priority and PCT Information for Patent: 10,058,536

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2015-073911	Mar 31, 2015

PCT Information
PCT Filed	March 31, 2016	PCT Application Number:	PCT/JP2016/060745
PCT Publication Date:	October 06, 2016	PCT Publication Number:	WO2016/159267

International Family Members for US Patent 10,058,536

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Cyprus	1122352
Denmark	3278801
European Patent Office	3278801
Spain	2760673
Croatia	P20192213