Details for Patent: 10,596,178

Which drugs does patent 10,596,178 protect, and when does it expire?

Patent 10,596,178 protects TABRECTA and is included in one NDA.

This patent has fifty-one patent family members in thirty-two countries.

Summary for Patent: 10,596,178

Title:	Tablet formulation of 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl) imidazo [1,2-B] [1,2,4] triazin-2-yl] benzamide
Abstract:	The present invention is related to tablets comprising of 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,-2-b][1,2,4]triazin-2-yl]benzamide, processes for the production thereof, and uses in the treatment of certain cancers.
Inventor(s):	Elisabete Goncalves, Christin Tauchmann, Shau-Fong Yen, Sudha Vippagunta, Zhixin Zong
Assignee:	Novartis AG
Application Number:	US16/134,162
Patent Claim Types: see list of patent claims	Compound; Dosage form;

US Patent 10,596,178: Scope, Claim Construction, and Patent Landscape for the Specified Imidazotriazine Tablet

US Patent 10,596,178 is directed to a highly specific tablet formulation containing the dihydrochloride salt of 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide. Claim 1 is a formulation claim, not a broad composition-of-matter claim. It requires a tablet with defined intragranular and extragranular phases and substantially fixed percentages for nine excipient or active-ingredient components.

The claim can block a generic or follow-on product only if that product practices every material limitation, including the two-phase manufacturing architecture, the specified dihydrochloride salt, and the claimed ingredient percentages. The patent does not, based on the supplied claim, cover every dosage form, every salt, every formulation, or every use of the active compound.

What does US Patent 10,596,178 claim?

Claim 1 requires all of the following:

1. A tablet.
2. The active ingredient identified by its full chemical name, or a pharmaceutically acceptable salt.
3. An intragranular phase.
4. An extragranular phase.
5. The specified ingredient set in each phase.
6. Approximately the stated percentage of each ingredient relative to total tablet weight.
7. The active ingredient in the intragranular phase as its dihydrochloride salt.

The claim is reproduced structurally below.

Claim element	Required limitation
Dosage form	Tablet
Active compound	2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide
Salt limitation	Dihydrochloride acid salt is specified in the intragranular phase
Intragranular active	About 23.54 wt%
Intragranular mannitol	About 20 wt%
Intragranular microcrystalline cellulose	About 20.26 wt%
Intragranular sodium dodecyl sulfate	About 0.2 wt%
Intragranular crospovidone	About 5 wt%
Intragranular povidone	About 4 wt%
Extragranular microcrystalline cellulose	About 20.75 wt%
Extragranular colloidal silicon dioxide	About 0.5 wt%
Extragranular crospovidone	About 5 wt%
Extragranular magnesium stearate	About 0.75 wt%

The listed percentages total 100%:

• Intragranular phase: 73.00%
• Extragranular phase: 27.00%

That numerical structure supports an interpretation that the claim describes a complete tablet composition rather than a partial formulation.

How broad is the active-ingredient limitation?

The active-ingredient limitation is chemically narrow despite the reference to a pharmaceutically acceptable salt.

The claim identifies one specific molecular scaffold:

• a fluoro-substituted benzamide;
• an N-methyl amide;
• an imidazo[1,2-b][1,2,4]triazine core;
• a quinolin-6-ylmethyl substituent.

A competitor using a materially different active compound would not ordinarily fall within the claim, even if it used the same excipients and manufacturing process.

The salt language requires closer construction. Claim 1 begins with the active compound "or a pharmaceutically acceptable salt thereof," but the formulation limitation then specifies approximately 23.54% of the dihydrochloride acid salt. The narrower ingredient limitation is likely to control the practical scope of the claim. A formulation using the free base, a monohydrochloride, a sulfate, a mesylate, or another salt could present a noninfringement position unless another claim independently covers that form.

What is the significance of the dihydrochloride salt?

The dihydrochloride limitation creates a material design-around axis. A competing product could potentially avoid literal infringement by using:

• the free base;
• a different pharmaceutically acceptable salt;
• a solvate or hydrate with a different claimed composition;
• a different active loading that falls outside the applicable "about" range.

That approach would not eliminate risk under the doctrine of equivalents. Equivalence would depend on whether the substituted salt performs substantially the same function in substantially the same way to achieve substantially the same result, and whether prosecution history limits that argument. The supplied claim alone does not establish the prosecution-history record.

What formulation architecture does the patent protect?

The claim protects a two-phase tablet architecture.

Intragranular phase

The intragranular phase contains the active salt, mannitol, microcrystalline cellulose, sodium dodecyl sulfate, crospovidone, and povidone. This indicates that the active ingredient is incorporated into a granulated intermediate with binders, disintegrant, filler, and surfactant.

Extragranular phase

The extragranular phase contains additional microcrystalline cellulose, colloidal silicon dioxide, crospovidone, and magnesium stearate. These materials are added after granulation and are likely associated with flow, lubrication, compression, and disintegration performance.

The phase allocation is legally important. A tablet containing the same ingredients at similar overall percentages may avoid literal infringement if the ingredients are assigned to different manufacturing phases. Conversely, a manufacturer may infringe even if it uses a different tablet weight, because the percentages are measured against total tablet weight rather than absolute milligram quantities.

How do the percentage limitations affect infringement risk?

The word "about" introduces tolerance, but it does not make the composition unrestricted. Courts generally interpret "about" in light of the specification, prosecution history, measurement methods, manufacturing variability, and the technology involved.

A quantitative infringement analysis would require:

1. The actual percentage of each component by total tablet weight.
2. The identity and form of the active salt.
3. The manufacturing records showing which components were intragranular and extragranular.
4. The analytical method used to calculate composition.
5. The patent specification and prosecution history defining the scope of "about."

The highest-risk formulation is one that reproduces the listed percentages and phase assignments substantially exactly. The risk decreases as a product departs from the claimed numerical profile, but there is no automatic safe harbor at a particular percentage deviation.

Formulation comparison

Product characteristic	High claim risk	Lower claim risk
Active form	Dihydrochloride salt	Free base or different salt
Dosage form	Tablet	Capsule, suspension, granule, or solution
Manufacturing phases	Same intragranular/extragranular allocation	Single-phase blend or different allocation
Active loading	Approximately 23.54 wt%	Materially different loading
Filler system	Mannitol plus specified microcrystalline cellulose levels	Different filler or materially different ratio
Surfactant	Approximately 0.2% sodium dodecyl sulfate intragranularly	No sodium dodecyl sulfate or different location
Lubricant	Approximately 0.75% magnesium stearate extragranularly	Different lubricant or materially different level
Disintegrant	Crospovidone in both phases at approximately 5% each	Crospovidone only in one phase or different level

Does the patent cover the active compound itself?

Not on the basis of the supplied claim.

Claim 1 is not a conventional composition-of-matter claim to the active molecule. It requires the molecule to be present in a particular tablet. A separate patent could protect:

• the active compound;
• a genus containing the compound;
• specific salts;
• crystalline or polymorphic forms;
• solvates and hydrates;
• intermediates;
• synthetic processes;
• therapeutic uses;
• dosing regimens;
• combination therapies;
• formulations different from the one claimed in US 10,596,178.

Those rights would form the broader patent estate. US 10,596,178 would occupy the formulation segment of that estate.

What patent families and related rights should be compared?

A complete freedom-to-operate review should separate the estate into distinct patent categories.

Patent category	Potential scope	Relevance to this tablet
Composition of matter	The active compound and close analogues	May block the active ingredient regardless of formulation
Salt and solid-state patents	Dihydrochloride, hydrates, polymorphs, crystallinity	May independently cover the claimed API form
Formulation patents	Excipients, ratios, release profile, tablet structure	US 10,596,178 falls in this category
Manufacturing patents	Granulation, blending, compression, coating, scale-up	May create process infringement risk
Method-of-use patents	Treatment of a disease or patient population	May affect labeling and induced infringement
Dosing patents	Dose, schedule, titration, treatment duration	Relevant to prescribing and label design
Combination patents	Use with another active agent	Relevant to combination products
Device or delivery patents	Specialized delivery systems	Less relevant to a conventional tablet

A patent landscape cannot be inferred from the formulation claim alone. The formulation patent may be only one member of a larger family, and its commercial significance depends on whether separate composition-of-matter or salt patents remain in force.

When does US Patent 10,596,178 lose exclusivity?

The patent's statutory expiration date cannot be calculated reliably from the grant number alone. US patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent term adjustment, terminal disclaimers, patent term extension, and other statutory adjustments.[2]

The relevant expiration analysis is:

Term component	Effect
Earliest effective nonprovisional filing date	Establishes the basic 20-year term
Patent term adjustment	Can extend the term for certain USPTO delays
Terminal disclaimer	Can limit the patent to the expiration of another patent
Patent term extension	May extend eligible regulatory patents under 35 U.S.C. § 156
Reexamination or post-grant proceedings	Can alter enforceability or claim scope, but do not automatically create a new term
Maintenance fees	Nonpayment can cause expiration before the statutory term

The grant date, March 24, 2020, is not the expiration date. A later-issued patent can expire based on an earlier priority or nonprovisional filing date.

What is the FDA Orange Book status of this patent?

A formulation patent is Orange Book-listable only if it claims an approved drug substance, drug product, or method of use as defined by the Hatch-Waxman framework. FDA listing depends on the NDA holder's submission and FDA's determination, not merely on the existence of a US patent.[3]

The claim could potentially qualify as a drug-product patent if the claimed tablet corresponds to an approved product. The supplied information does not establish:

• the associated NDA;
• the approved product name;
• whether the patent is listed in the Orange Book;
• the listed patent use code;
• the date of any Orange Book listing;
• whether the patent has been delisted or challenged.

A formulation patent that is not listed in the Orange Book may still be enforceable in ordinary patent litigation, but it may not generate the same Paragraph IV certification or 30-month-stay consequences under the ANDA process.

How do Paragraph IV challenges apply?

An ANDA applicant seeking approval before expiration of an Orange Book-listed patent may submit a Paragraph IV certification alleging that the patent is invalid, unenforceable, or will not be infringed.[4]

For this claim, a Paragraph IV challenge could target:

• lack of written description or enablement;
• indefiniteness of "about";
• anticipation by a prior tablet formulation;
• obviousness based on known excipient combinations and routine optimization;
• lack of novelty in the phase-specific composition;
• noninfringement based on a different salt, phase allocation, dosage form, or composition.

The most plausible technical defenses would focus on whether the exact combination of ingredients, phase assignments, and concentrations was disclosed or rendered obvious before the relevant filing date. The unusually precise percentages may support patentability if they produce unexpected dissolution, stability, bioavailability, manufacturability, or tablet-performance results. Those same percentages can create vulnerability if they reflect routine formulation optimization without demonstrated unexpected results.

A Paragraph IV filing does not itself invalidate the patent. Litigation, settlement, or a court decision determines the commercial outcome.

What litigation and settlement issues affect the patent?

The supplied information does not establish a filed infringement action, ANDA challenge, settlement agreement, stipulated judgment, or post-grant proceeding involving US 10,596,178. The patent number alone does not prove that litigation has occurred.

If an ANDA dispute exists, the key documents would include:

• the Paragraph IV notice letter;
• the patent owner's complaint;
• the ANDA applicant's proposed formulation;
• claim-construction orders;
• infringement and invalidity opinions;
• any consent judgment;
• any settlement and license terms;
• FDA's approval date and any agreed launch date.

A settlement could provide a generic license before patent expiration, an authorized-generic arrangement, a delayed launch date, or restrictions tied to specific strengths or formulations. The economic effect depends on whether the settlement covers only this formulation patent or also broader compound and salt patents.

How strong is the patent estate based on claim 1?

Strengths

Claim 1 has several features that may make it commercially useful:

• It is directed to a finished dosage form rather than a broad laboratory composition.
• It defines both intragranular and extragranular phases.
• It specifies the API salt.
• It claims a complete quantitative formulation.
• It may capture the commercial tablet closely if the product uses the claimed formulation.

These limitations can make design-around more difficult for a manufacturer seeking to reproduce the reference product exactly.

Weaknesses

The same limitations narrow the enforceable perimeter:

• A capsule or non-tablet product falls outside the claim.
• A different salt may avoid literal infringement.
• A different manufacturing sequence may avoid the phase limitations.
• A materially different excipient ratio may avoid the quantitative limitations.
• The term "about" may create claim-construction disputes.
• A prior-art formulation may challenge novelty or obviousness.
• The claim may have limited value if the commercial product changes formulation.

The claim is therefore potentially strong against an exact-copy tablet but weak against products deliberately designed around its salt, phase allocation, or quantitative profile.

What generic launch scenarios exist?

Scenario	Likely result
Generic duplicates the reference tablet	High infringement exposure if the patent is enforceable and unexpired
Generic uses the same active but a different salt	Potentially lower risk, subject to salt and compound patents
Generic uses the free base with a different formulation	May avoid claim 1, but broader API rights may remain
Generic uses a capsule	Outside claim 1, subject to other patent claims
Generic uses the same ingredients but a different phase allocation	Possible noninfringement position
Generic obtains a license	Launch timing depends on negotiated rights
Patent is not Orange Book-listed	No automatic Paragraph IV pathway for this patent, although litigation remains possible
Patent is invalidated or expires	Launch remains subject to other unexpired patents and regulatory exclusivity

A successful design-around of this formulation claim does not necessarily create freedom to launch. Composition-of-matter, salt, polymorph, method-of-use, and manufacturing patents may independently delay entry.

What regulatory exclusivity is separate from patent protection?

FDA exclusivity is distinct from patent rights. Depending on the approved product and regulatory pathway, relevant periods could include:

• five-year new chemical entity exclusivity;
• three-year exclusivity for certain new clinical investigations;
• orphan-drug exclusivity;
• pediatric exclusivity;
• other product-specific statutory protections.

The claim supplied does not identify the approved product, NDA, active ingredient status, or FDA exclusivity category. No regulatory exclusivity period can be assigned from the patent claim alone. FDA's Orange Book records and the applicable approval documents control the regulatory analysis.[3]

What manufacturing and intellectual-property barriers remain?

The principal manufacturing barrier is reproduction of the claimed phase structure with the claimed quantitative composition. A generic manufacturer would need to assess:

• whether the active dihydrochloride salt is commercially available;
• whether the claimed salt has a protected crystal form;
• whether the granulation process is separately patented;
• whether the target dissolution profile requires the claimed excipient system;
• whether sodium dodecyl sulfate is necessary for wetting or dissolution;
• whether the specified povidone and crospovidone levels are necessary for tablet integrity;
• whether the tablet can be redesigned without compromising bioequivalence.

The patent may have greater practical value if the formulation is necessary to achieve bioequivalence or acceptable stability. It may have less value if multiple alternative formulations can satisfy FDA's bioequivalence requirements.

How does this patent compare with compound and method-of-use patents?

Right type	Breadth	Typical commercial effect
Compound patent	Broadest, if it covers the active molecule	Can block nearly all products containing the molecule
Salt or polymorph patent	Intermediate	Can block a specific commercial API form
Formulation patent	Narrower	Blocks only products practicing the claimed dosage form or composition
Method-of-use patent	Depends on claim language and label	Can affect labeled indications and induced infringement
Manufacturing patent	Process-specific	Can restrict production methods even where product claims are avoided

US 10,596,178 should be valued as a product-formulation asset. It should not be treated as a substitute for a composition-of-matter patent.

Key Takeaways

• US 10,596,178 claim 1 is a narrow tablet formulation claim.
• The claim requires the specified imidazotriazine active, with the dihydrochloride salt expressly identified in the intragranular phase.
• It requires an intragranular phase totaling approximately 73% of the tablet and an extragranular phase totaling approximately 27%.
• The claim covers specific excipients, percentages, and phase assignments.
• A product using a different dosage form, salt, manufacturing phase allocation, or materially different composition may have a noninfringement position.
• The patent does not, from the supplied claim, independently establish coverage of the active compound, a particular polymorph, a therapeutic use, or a manufacturing process.
• The grant date is not the expiration date. Expiration requires the earliest effective nonprovisional filing date and any applicable term adjustments.
• Orange Book listing, Paragraph IV exposure, litigation, settlement terms, and FDA exclusivity cannot be established from the claim text alone.
• The patent is most commercially significant against an exact-copy tablet and less significant against a well-designed alternative formulation.
• Any launch analysis must evaluate the full compound, salt, solid-state, formulation, method-of-use, manufacturing, and regulatory estate.

FAQs

Can a generic avoid US 10,596,178 by changing only the tablet weight?

Usually not if the percentages remain substantially the same. Because the claim expresses the ingredients as percentages of total tablet weight, changing the tablet's absolute weight while preserving the claimed percentages may still practice the claim.

Does using a different brand of microcrystalline cellulose avoid the patent?

Not necessarily. The claim identifies microcrystalline cellulose by material type, not by supplier. A different manufacturer may still supply the same claimed excipient.

Can a manufacturer avoid infringement by mixing all ingredients together?

Potentially, but the result depends on whether the claim requires the claimed intragranular and extragranular phase allocation and whether the actual process and product satisfy those limitations. A single-phase blend presents a stronger design-around argument than a process reproducing the claimed phase structure.

Does FDA approval of an alternative formulation eliminate patent risk?

No. FDA approval addresses regulatory requirements. It does not determine whether the formulation infringes an unexpired patent or whether other patents cover the active ingredient or its use.

Can the patent block a product using the same active compound in a capsule?

Claim 1 is limited to a tablet. A capsule would ordinarily fall outside that claim, but separate claims in the patent or other patents could cover the active compound, salt, formulation, method of use, or manufacturing process.

References

1. United States Patent No. 10,596,178, claim 1 (2020).
2. 35 U.S.C. § 154 (2023). Patent term.
3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations (Orange Book).
4. 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (2023). Paragraph IV patent certification.
5. Manual of Patent Examining Procedure, §§ 2111, 2111.03, 2111.04 (U.S. Patent and Trademark Office, 2024). Claim construction and relative terminology.

Drugs Protected by US Patent 10,596,178

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis Pharm	TABRECTA	capmatinib hydrochloride	TABLET;ORAL	213591-001	May 6, 2020		RX	Yes	No			Y
Novartis Pharm	TABRECTA	capmatinib hydrochloride	TABLET;ORAL	213591-002	May 6, 2020		RX	Yes	Yes			Y

International Family Members for US Patent 10,596,178

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3172209		301208	Netherlands
European Patent Office	3172209		CA 2022 00056	Denmark
European Patent Office	3172209		2022C/558	Belgium
European Patent Office	3172209		122022000076	Germany
European Patent Office	3172209		51/2022	Austria
European Patent Office	3172209		22C1058	France