United States Patent 11,253,515: Claim Scope, Formulation Protection, and Patent-Landscape Analysis

US 11,253,515 protects capsule formulations containing the specified indazole-benzamide active pharmaceutical ingredient, an acidulant, and defined intragranular and extragranular excipient arrangements. The broadest claim is a composition claim directed to the physical placement of the active ingredient and acidulant in the same solid intragranular admixture. The patent does not broadly claim the active ingredient itself, its therapeutic use, or every dosage form.

The principal commercial risk is a capsule product using the same active ingredient with acidulant-containing granules. The principal design-around opportunity is to alter the acidulant location, eliminate the acidulant, change the manufacturing architecture, or use a formulation that does not satisfy the claimed component structure.

What does US Patent 11,253,515 protect?

The patent protects a pharmaceutical capsule composition comprising:

An intragranular component;
An extragranular component;
The specified active ingredient in the intragranular component;
At least one acidulant in the intragranular component; and
The active ingredient and acidulant present as a solid admixture in that intragranular component.

The active ingredient is:

N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide.

Claim 1 is the key scope-defining claim. It is an open-ended composition claim because it uses "comprising." Under established U.S. claim-construction principles, a "comprising" claim generally permits additional unrecited ingredients or steps, provided every required limitation remains present (USPTO, n.d.-a).

The claim is narrower than a claim to the active pharmaceutical ingredient or a generic capsule. A potentially infringing product must contain the claimed active ingredient, acidulant, intragranular component, extragranular component, and solid admixture relationship.

How broad is independent claim 1?

Claim 1 has five material limitations.

Limitation	Scope
Pharmaceutical capsule composition	Requires a capsule dosage form or composition intended for encapsulation
Intragranular component	Requires material incorporated within granules
Extragranular component	Requires material outside the granules before or during capsule filling
Specified active ingredient	Covers the named chemical compound, subject to ordinary claim-construction issues concerning salts, solvates, and stereochemistry
Acidulant in solid admixture with active ingredient	Requires the acidulant and active ingredient to be present together in the intragranular solid mixture

The claim does not expressly require:

A particular capsule shell;
A particular capsule size;
A specific granulation process;
Wet granulation or dry granulation;
A particular acidulant concentration;
A specific release profile;
A particular therapeutic indication;
A particular particle size, except for micronized fumaric acid in dependent claim 6;
The listed excipients in claims 12 through 18.

The most important limitation is the requirement that the active ingredient and acidulant be present in the intragranular component "as a solid admixture." That language distinguishes the protected formulation from a capsule in which the acidulant is only extragranular, incorporated into the capsule shell, dissolved in a coating, or omitted entirely.

What acidulants are protected?

Claims 2 through 9 define the acidulant subgenus and specific species.

Claim	Acidulant limitation
1	At least one acidulant
2	Organic acidulant
3	Tartaric acid, maleic acid, fumaric acid, citric acid, or betaine hydrochloride
4	Tartaric acid
5	Fumaric acid
6	Micronized fumaric acid
7	Maleic acid
8	Citric acid
9	Betaine hydrochloride

Claim 1 is broader than claims 2 through 9 because it is not limited to organic acidulants or the five named alternatives. A formulation using another acidulant could fall within claim 1 if the other limitations are met.

Claim 6 creates a narrower formulation position for micronized fumaric acid. It does not define a numerical particle-size range. Consequently, "micronized" would likely require construction using the patent specification, prosecution history, technical context, and evidence concerning ordinary pharmaceutical usage.

Betaine hydrochloride is included in the claim set even though it is chemically distinct from the simple carboxylic acid examples. Its express inclusion expands the practical acidulant coverage beyond conventional organic acids.

What molar ratios and dosage strengths are covered?

Claim 10 covers an active ingredient-to-acidulant molar ratio from about 0.5 to about 2. The word "about" introduces a potential boundary-construction issue. The enforceable range would depend on the specification, prosecution history, analytical precision, and the meaning that a skilled pharmaceutical formulator would assign to the stated range.

Claim 11 covers 25 mg to 800 mg of active ingredient in the intragranular component. Claims 21 and 22 narrow this to approximately 100 mg and 200 mg, respectively.

The claim language specifies the amount in the intragranular component rather than clearly stating the total capsule fill weight. That distinction matters. A capsule containing 100 mg of active ingredient in the intragranular component may fall within claim 21 even if the total capsule contains additional active ingredient outside the granules, although the overall claim must still satisfy claim 1 and the applicable dependent limitations.

What excipients and formulation architectures are protected?

Claims 12 through 18 protect selected excipient arrangements.

Intragranular excipients

Claim 12 permits the intragranular component to contain:

Lactose;
Hypromellose;
Crospovidone;
Magnesium stearate; or
Any combination of two or more.

Extragranular excipients

Claim 13 permits the extragranular component to contain:

Microcrystalline cellulose;
Crospovidone;
Colloidal silicon dioxide;
Magnesium stearate; or
Any combination of two or more.

Combined architecture

Claim 14 requires both:

An intragranular component containing one or more of the claim 12 excipients; and
An extragranular component containing one or more of the claim 13 excipients.

Claims 15 and 16 add quantitative composition ranges. Claim 17 specifies anhydrous lactose. Claim 18 provides a detailed formulation with approximate weight percentages.

Ingredient	Claim 18 amount
Active ingredient	44.44% w/w
Tartaric acid	13.11% w/w
Anhydrous lactose	28.89% w/w
Hypromellose	4.00% w/w
Microcrystalline cellulose	2.97% w/w
Crospovidone	5.28% w/w
Colloidal silicon dioxide	0.25% w/w
Magnesium stearate	1.06% w/w
Total	100.00% w/w

Claim 18 is commercially significant because it identifies a fully specified composition rather than only a broad ingredient class. Claims 19 and 20 then associate that formulation with approximately 100 mg and 200 mg of active ingredient in the intragranular component.

Which claims are strongest for enforcement?

The practical hierarchy is:

Claim 1: broadest formulation claim;
Claim 3: limits the acidulant to five named substances;
Claim 4: tartaric acid formulation;
Claim 10: ratio-defined formulation;
Claim 11: dosage-range formulation;
Claim 14: specified intra- and extragranular excipient arrangement;
Claims 15 and 16: quantitative composition ranges;
Claim 18: detailed composition;
Claims 19 and 20: detailed composition with 100 mg or 200 mg intragranular dosage;
Claims 21 and 22: broader formulation coverage tied to 100 mg or 200 mg intragranular dosage.

Claim 1 has the greatest literal breadth but may face more substantial validity and construction disputes because it reaches any acidulant and does not impose a quantitative acidulant range. Claim 18 is narrower but may provide a clearer infringement case where a competitor’s product closely matches the listed composition.

The claims that combine the solid-admixture requirement, tartaric acid, defined excipients, and the 100 mg or 200 mg strength are likely to be the most commercially focused claims.

What formulation design-arounds exist?

A competitor could reduce literal infringement risk through several formulation changes.

Design-around approach	Likely claim issue
Place all acidulant extragranularly	May avoid the requirement that acidulant be in the intragranular component
Omit acidulant	Avoids the central acidulant limitation
Use a liquid, coated, or non-solid acidulant system	Creates an argument against the solid-admixture limitation
Use a different dosage form	May avoid the capsule-composition limitation
Use a formulation without an extragranular component	May avoid claim 1 if no extragranular component exists
Use a different active pharmaceutical ingredient	Avoids the named-compound limitation
Alter the granulation structure	May avoid claims requiring the claimed component allocation
Use different excipients	Avoids claims 12 through 18, but not necessarily claim 1
Use a ratio outside approximately 0.5 to 2	May avoid claim 10 while remaining exposed to claim 1
Use a dosage outside 25 mg to 800 mg	May avoid claim 11, but not necessarily claim 1

A design-around must be evaluated against the entire claim, including the doctrine of equivalents. A formulation that relocates acidulant from the intragranular to the extragranular phase may present a stronger noninfringement position than a formulation that makes only minor changes to excipient quantities. Under 35 U.S.C. § 271, literal infringement and infringement under the doctrine of equivalents are separate issues.

Does US 11,253,515 cover the active ingredient itself?

No. The supplied claims are directed to pharmaceutical capsule compositions. They do not claim:

The active ingredient as a chemical compound;
A crystalline or amorphous form;
A salt or solvate of the active ingredient;
A method of synthesizing the active ingredient;
A method of treating a disease;
A broad class of kinase inhibitors;
A tablet, injectable, suspension, or other dosage form.

Separate compound, salt, crystal-form, process, method-of-use, or formulation patents could create additional barriers. Those rights cannot be established from the claims supplied here.

What is the likely patent landscape around this formulation?

The relevant landscape should be divided into six patent categories.

Patent category	Relevance to this product
Compound patents	May control the active ingredient independently of the capsule formulation
Salt and polymorph patents	May control solid forms used in manufacturing
Formulation patents	Include US 11,253,515 and potentially related family members
Method-of-use patents	May restrict treatment of particular diseases or patient populations
Manufacturing patents	May protect granulation, particle-size control, or processing conditions
Regulatory exclusivity	May delay approval even after patent issues are resolved

US 11,253,515 is a formulation patent, not a complete exclusivity package. Commercial freedom to launch depends on the full patent family, related U.S. applications, terminal disclaimers, patent-term adjustment, Orange Book listing status, regulatory exclusivity, and any litigation or settlement agreements.

When does the patent expire?

The expiration date cannot be calculated from the claim text alone. U.S. utility patents generally receive a term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory rules (35 U.S.C. §§ 154, 156).

The patent number establishes an issued U.S. patent, but the claims supplied do not identify:

The earliest priority date;
The U.S. nonprovisional filing date;
Patent-term adjustment;
Patent-term extension;
Terminal disclaimer status;
Continuation or divisional relationships.

Those data control the legally operative expiration date.

What is the Orange Book status?

Orange Book status cannot be determined from the claim language. The FDA Orange Book identifies patents submitted by an approved new drug application holder and accepted for listing under FDA procedures. A patent may exist without being listed, and a listed patent may not cover every formulation or dosage form marketed by the sponsor (FDA, n.d.-a).

If the patent is listed for an approved product, it could affect an abbreviated new drug application through a patent certification, including a Paragraph IV certification. If it is not listed, it may still support patent litigation but would not necessarily create an Orange Book-based Paragraph IV stay.

Are Paragraph IV challenges or generic launch risks established?

No Paragraph IV challenge, ANDA litigation event, or generic settlement can be established from the claims supplied. The commercial risk analysis would depend on whether:

The active ingredient has an approved reference product;
US 11,253,515 is listed for that product;
A generic applicant seeks the same capsule formulation;
The applicant submits a Paragraph IV certification;
The patent owner files an infringement action within the statutory period;
The parties enter a launch-date or license settlement.

For a product that exactly reproduces the claimed capsule architecture, the principal litigation issue would likely be factual proof of the intragranular and extragranular composition. ANDA product information, manufacturing records, discovery, and laboratory analysis could become material evidence.

Does biosimilar risk apply?

Biosimilar risk does not apply to this patent on the facts provided. The claims cover a small-molecule pharmaceutical capsule, not a biologic. A competitor would ordinarily pursue an ANDA or another small-molecule pathway rather than a biosimilar application under the Public Health Service Act.

The relevant competitive threat is generic entry, not biosimilar substitution.

What litigation and licensing issues matter?

The supplied claim set contains no information establishing:

Patent litigation;
Inter partes review;
Post-grant review;
Licensing transactions;
Co-development agreements;
Settlement agreements;
Authorized-generic arrangements;
Patent ownership transfers.

The patent owner’s commercial position should be assessed against the complete family and chain of title. A formulation patent may be licensed separately from compound rights. A settlement could also permit an authorized launch before patent expiration without eliminating the patent’s validity or enforceability.

How strong is the patent estate?

The formulation claim has moderate commercial strength and a clear design-around profile.

Strengths include:

A specific active ingredient;
A required intragranular location for the active ingredient and acidulant;
Coverage of multiple acidulants;
Coverage of broad excipient categories;
Specific tartaric-acid formulations;
Defined 100 mg and 200 mg embodiments;
A detailed composition claim that may track a commercial product closely.

Weaknesses include:

The claims do not protect the active ingredient itself;
The claim requires a particular capsule architecture;
The acidulant must be in the same intragranular solid admixture;
Several dependent claims are limited to narrow excipient and percentage ranges;
Alternative dosage forms and acidulant placement may avoid literal infringement;
The term "solid admixture," "about," and "micronized" may generate construction disputes;
Prior-art risk may be concentrated in pharmaceutical granulation and acidification techniques.

The strongest practical enforcement position would arise where a competitor uses the named active ingredient, tartaric acid, the listed excipients, the same intragranular/extragranular allocation, and approximately 100 mg or 200 mg strength.

Key Takeaways

US 11,253,515 is a formulation patent, not a compound patent.
Claim 1 requires the active ingredient and acidulant to be in the same intragranular solid admixture.
Tartaric acid is the most commercially prominent species in the dependent claims.
Claims 15 through 20 protect increasingly specific composition and dosage embodiments.
A capsule with acidulant only in the extragranular phase may present a strong design-around position.
The claims do not establish Orange Book listing, Paragraph IV activity, litigation, licensing, or patent expiration.
Biosimilar analysis is inapplicable because the claims concern a small-molecule capsule.
Full launch-risk analysis requires the related compound, formulation, manufacturing, method-of-use, and regulatory-exclusivity rights.

FAQs

What is the central limitation in US 11,253,515?

The central limitation is the presence of the named active ingredient and at least one acidulant together as a solid admixture in the intragranular component of a capsule composition.

Does a capsule with tartaric acid outside the granules infringe claim 1?

It may avoid literal infringement of claim 1 because the claim requires the acidulant to be in the intragranular component. The complete formulation and potential doctrine-of-equivalents issues would still control the final analysis.

Are 100 mg and 200 mg capsules separately protected?

Yes. Claims 19, 20, 21, and 22 expressly address approximately 100 mg and 200 mg quantities in the intragranular component, although the claims differ in the extent of their formulation limitations.

Can a tablet infringe this patent?

A tablet would generally have a substantial noninfringement argument because the claims require a pharmaceutical capsule composition. That issue would depend on whether the tablet can satisfy the ordinary meaning of the claimed capsule limitation.

Does changing tartaric acid to citric acid avoid the patent?

No. Citric acid is expressly covered by claim 8 and may also fall within the broader acidulant language of claim 1. Changing the acidulant alone may not avoid infringement.

References

Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

Patent Act, 35 U.S.C. §§ 154, 156, 271.

United States Patent and Trademark Office. (n.d.-a). Manual of patent examining procedure § 2111.03: Effect of transitional phrases.

United States Patent and Trademark Office. (n.d.-b). Manual of patent examining procedure § 2111: Claim interpretation; broadest reasonable interpretation.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	11,253,515	⤷ Start Trial	Y				⤷ Start Trial
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-002	Aug 15, 2019		RX	Yes	Yes	11,253,515	⤷ 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	2018302170	⤷ Start Trial
Brazil	112020000793	⤷ Start Trial
Canada	3069339	⤷ Start Trial
China	110913842	⤷ Start Trial
China	121401264	⤷ Start Trial
European Patent Office	3654952	⤷ Start Trial
Israel	271759	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,253,515

Which drugs does patent 11,253,515 protect, and when does it expire?

Summary for Patent: 11,253,515