United States Patent 9,339,472: Saxagliptin Combination-Tablet Claims, Patent Scope, and Competitive Landscape

U.S. Patent No. 9,339,472 protects a layered oral combination formulation in which a preformed tablet containing a drug other than saxagliptin is surrounded by three polyvinyl-alcohol-based coating layers. Saxagliptin, preferably saxagliptin hydrochloride, is incorporated into the intermediate coating rather than into the core tablet. The patent is directed to dosage-form architecture, coating composition, and component-concentration ranges, not to saxagliptin as an active pharmaceutical ingredient.

The principal infringement risk is limited to products that place saxagliptin in a second coating layer around a separate tablet core containing another drug. A conventional bilayer tablet, a single-layer tablet containing both active ingredients, a capsule, or a product using saxagliptin in the core would generally fall outside the literal language of the independent claims, subject to equivalents and the patent’s prosecution history.

What does U.S. Patent 9,339,472 protect?

The patent protects a combination formulation with four structural elements:

A drug tablet containing an active ingredient other than saxagliptin.
An inner seal coating containing polyvinyl alcohol.
A second coating containing saxagliptin or a pharmaceutically acceptable salt, together with polyvinyl alcohol and specified excipient categories.
A third outer protective coating containing polyvinyl alcohol.

The independent claims are claims 1 and 6. Claims 2-5 and 7-20 add salt, excipient, and concentration limitations.

Claim group	Core limitations	Principal legal effect
Claims 1-5	Weight ranges measured against the drug tablet; saxagliptin in second coating; PVA in all three layers	Broadest composition-based claim set
Claims 6-20	Weight ranges measured within individual coating layers; detailed PVA, PEG, talc, titanium dioxide, and saxagliptin ranges	Narrower but more formulation-specific claims
Claims 2 and 7	Saxagliptin hydrochloride	Covers the hydrochloride salt specifically
Claims 3-5 and 8-10	Polyethylene glycol in one or more layers	Adds PEG-containing embodiments
Claims 11-13 and 18-20	PVA and excipient subranges in inner and outer layers	Narrows toward a defined coating composition
Claims 14-17	Saxagliptin concentration and coating-material composition	Targets the intermediate drug-containing coating

The patent should be read as a formulation patent, not as a patent covering every saxagliptin combination product.

How do the independent claims define infringement?

Claim 1 uses tablet-relative weight ranges

Claim 1 requires:

Polyvinyl alcohol in the inner seal coating at 0.5% to 50% by weight of the drug tablet;
Saxagliptin at 0.1% to 70% by weight of the drug tablet;
The polymer, plasticizer, and glidant in the second coating at 1% to 70% by weight of the drug tablet;
Polyvinyl alcohol in the second coating polymer;
Polyvinyl alcohol in the third outer coating;
A core tablet containing a drug other than saxagliptin.

This is a relatively broad numerical framework because the percentages are calculated against the weight of the drug tablet, rather than solely against the weight of each coating layer.

The claim does not require a particular core drug. Metformin, dapagliflozin, empagliflozin, rosiglitazone, pioglitazone, or another active ingredient could potentially satisfy the “drug other than saxagliptin” limitation if the remaining structural and compositional requirements are met.

Claim 6 uses layer-relative weight ranges

Claim 6 requires:

PVA comprising about 10% to about 95% of the inner seal coating;
Saxagliptin comprising about 0.25% to about 70% of the second coating;
PVA comprising about 30% to about 99.5% of the second coating;
PVA comprising about 10% to about 95% of the outer protective coating;
A non-saxagliptin drug tablet as the core.

Claim 6 is narrower in structure but may be more commercially relevant because it describes the composition of each coating layer directly. A product may avoid claim 6 while still implicating claim 1 if its formulation falls within the tablet-relative ranges of claim 1.

What formulations are protected by U.S. Patent 9,339,472?

The patent’s protected architecture is a coated-core system:

Outer protective PVA coating
        |
Saxagliptin-containing PVA coating
        |
Inner seal PVA coating
        |
Tablet core containing another drug

The claims cover the following formulation characteristics:

Formulation characteristic	Covered by claims?
Saxagliptin in a coating rather than the tablet core	Yes
Separate tablet core containing another drug	Yes
PVA in inner, intermediate, and outer layers	Yes
Saxagliptin hydrochloride	Yes, under claims 2 and 7
Polyethylene glycol in one or more coating layers	Yes, under dependent claims
Talc and titanium dioxide	Yes, in the specific embodiments of claims 13, 17, and 20
A conventional bilayer tablet	Not expressly covered
Saxagliptin and the second drug blended in one core	Not expressly covered
Saxagliptin capsule formulation	Not expressly covered
Saxagliptin in an uncoated tablet	Not expressly covered
A product without PVA in one required layer	Potential design-around, subject to equivalents

The claims are composition claims. They do not expressly require a particular release profile, dissolution specification, coating thickness, manufacturing machine, tablet shape, or therapeutic indication.

How do claims 1 and 6 differ?

The principal distinction is the denominator used for the percentage limitations.

Issue	Claim 1	Claim 6
Percentage basis	Weight of the drug tablet	Weight of the relevant coating layer
Inner coating polymer	0.5%-50% of drug tablet	About 10%-95% of inner layer
Saxagliptin	0.1%-70% of drug tablet	About 0.25%-70% of second coating
Intermediate coating excipients	1%-70% of drug tablet	PVA about 30%-99.5% of second coating
Outer coating polymer	0.5%-50% of drug tablet	About 10%-95% of outer layer
Practical effect	Broader tablet-level formulation coverage	More detailed layer-composition coverage

A formulation may satisfy both claims, only claim 1, only claim 6, or neither. Claim construction will turn on how “drug tablet,” “coating layer,” “about,” and the weight percentages are interpreted and measured.

Does the patent cover saxagliptin hydrochloride?

Yes. Claims 2 and 7 expressly cover saxagliptin hydrochloride.

The independent claims already cover “saxagliptin or a pharmaceutically acceptable salt thereof.” The dependent hydrochloride claims therefore provide a more specific fallback position. They are commercially relevant because saxagliptin hydrochloride is the salt form used in marketed saxagliptin products, including Onglyza and combination products based on saxagliptin.

The presence of a hydrochloride limitation does not mean that the independent claims are restricted to the hydrochloride salt. A different pharmaceutically acceptable salt may fall within claims 1 or 6 if the formulation architecture and numerical limitations are met.

What excipients are protected?

The patent identifies several coating excipient classes and specific compositions.

Polyethylene glycol

Claims 3-5 and 8-10 cover PEG in the inner, second, or outer coating. PEG functions primarily as a plasticizer in the described coating systems.

Talc and titanium dioxide

Claims 13, 17, and 20 describe formulations containing:

About 40% PVA;
About 20% PEG;
About 15% talc;
About 25% titanium dioxide.

These percentages are stated for the relevant coating layer or coating material. The claims may therefore be relevant to a product using a standard white film-coating system with PVA, PEG, talc, and titanium dioxide, provided that the layer structure and saxagliptin placement also correspond.

Glidant and opacifying agent

Claim 1 requires a second coating containing a coating polymer, plasticizer, and glidant. Claim 15 adds an opacifying agent. Claim 15 is narrower than claim 1 because the opacifying-agent limitation is not required in the independent claim.

What products could potentially fall within the patent?

Potentially relevant products have the following profile:

A combination product containing saxagliptin and another active ingredient;
The other active ingredient is formulated as a tablet core;
Saxagliptin is applied in a coating over that core;
The saxagliptin coating is separated from the core by an inner PVA seal coat;
An outer PVA protective coat is applied over the saxagliptin layer;
The relevant percentages fall within the claimed ranges.

A product based on saxagliptin/metformin is the most obvious commercial comparison because Kombiglyze XR contains saxagliptin and metformin. Qtern, which combines saxagliptin with dapagliflozin, is another relevant market product. Marketed product architecture must be confirmed from manufacturing and regulatory records; public labeling alone generally does not disclose the full layer-by-layer composition.

Product or product type	Apparent relevance
Onglyza	Saxagliptin product, but not a combination product
Kombiglyze XR	Saxagliptin/metformin combination; commercial architecture must be compared with the claims
Qtern	Saxagliptin/dapagliflozin combination; commercial architecture must be compared with the claims
Generic saxagliptin tablets	Usually outside the combination limitation
Generic saxagliptin/metformin tablets	Potential risk depends on tablet architecture and coating composition
Single-core combination tablet	May avoid the separate drug-tablet and saxagliptin-coating limitations
Co-packaged tablets	May avoid the “combination formulation” architecture if no single coated dosage form contains the claimed layers

When does U.S. Patent 9,339,472 lose exclusivity?

U.S. Patent 9,339,472 issued on May 17, 2016. Its ordinary patent-term expiration must be calculated from the relevant nonprovisional application filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.

The patent number alone does not establish the final enforceable expiration date. The controlling record is the USPTO patent file, including:

The earliest effective nonprovisional filing date;
Any continuation or divisional relationship;
Patent-term adjustment;
Terminal disclaimer;
Patent-term extension;
Reexamination or post-grant proceedings.

The patent does not appear to be an Orange Book exclusivity statement by itself. Patent expiry and FDA-listed product protection are separate questions. A patent can remain in force without being listed for a particular approved product, and an FDA-listed patent can have practical importance only for the drug product and use to which it is linked.

What is the Orange Book status of U.S. Patent 9,339,472?

The Orange Book question must be evaluated at the approved-product level. FDA patent listings are associated with a specific NDA and generally identify patents covering the drug substance, drug product, or an approved method of use.

For this patent, the relevant inquiry is whether AstraZeneca or another NDA holder listed U.S. 9,339,472 against:

Onglyza;
Kombiglyze XR;
Qtern;
Another saxagliptin-containing NDA.

A formulation patent directed to a particular coated combination architecture may be listed as a drug-product patent if the NDA holder submitted it for listing and FDA accepted the listing. It would not automatically be listed against every saxagliptin product.

The applicable Orange Book analysis should distinguish:

Issue	Meaning
Patent listed in Orange Book	May trigger a Paragraph IV certification or 30-month-stay framework for an ANDA
Patent not listed	Does not ordinarily create an Orange Book Paragraph IV obligation
Patent in force but not listed	May still support a separate infringement action
Listed patent expired	No continuing patent-based ANDA stay from that patent
Patent-use code	Limits the listed method-of-use scope, where applicable

FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations is the controlling public source for current patent and exclusivity listings. [1]

Are Paragraph IV challenges likely for this patent?

A Paragraph IV challenge is relevant only if the patent is listed for the reference product and the ANDA applicant certifies that the patent is invalid, unenforceable, or will not be infringed.

For U.S. 9,339,472, a generic applicant would likely evaluate several noninfringement routes:

Use a core tablet that does not have the claimed three-layer architecture.
Place saxagliptin in the core rather than in the second coating.
Omit PVA from one required coating layer.
Use a conventional bilayer or multilayer tablet.
Use a capsule or co-packaged dosage form.
Select coating quantities outside the claimed ranges.
Challenge the claims for anticipation or obviousness based on film-coating and combination-tablet prior art.
Challenge the written-description or enablement basis for broad percentage ranges, if supported by the prosecution record.

A Paragraph IV certification would not automatically resolve infringement. The patent holder could sue within the statutory period, potentially triggering the ANDA approval stay under the Hatch-Waxman framework.

What generic entry risks exist?

The generic entry risk is architecture-dependent.

Low-to-moderate risk: conventional combination tablet

A conventional tablet that places both active ingredients in one core, or uses separate layers without saxagliptin in a PVA intermediate coating, has a stronger noninfringement position.

Higher risk: coated-core design

A generic product that deliberately reproduces a drug-containing core surrounded by inner, saxagliptin-containing, and outer PVA coatings faces a direct literal-infringement risk if the numerical limitations are satisfied.

Intermediate risk: incomplete public formulation data

Regulatory labels generally do not disclose coating-layer mass, polymer percentages, or manufacturing sequence in enough detail to determine infringement. Discovery, ANDA product records, batch records, and reverse engineering would be important in litigation.

Generic design	Claim risk
Saxagliptin in tablet core	Lower
Second drug in tablet core, saxagliptin in separate outer coating	Higher
No inner PVA seal layer	Lower for literal infringement
No outer PVA protective layer	Lower for literal infringement
PVA replaced with another film former	Lower, subject to equivalents
Same architecture but out-of-range concentrations	Depends on claim construction and equivalents
Two tablets in one package	Generally lower
Capsule containing separate pellets	Generally lower unless claim language is met

How strong is the patent estate for this formulation?

The strength of U.S. 9,339,472 depends less on the novelty of saxagliptin and more on the patent’s ability to distinguish the claimed multilayer coating system from known film-coated tablets and combination dosage forms.

Strengths

The claims require a specific physical arrangement.
Saxagliptin must be in an intermediate coating rather than merely present somewhere in the dosage form.
The inner and outer PVA layers create multiple structural limitations.
Dependent claims provide narrower fallback positions for saxagliptin hydrochloride, PEG, talc, titanium dioxide, and defined percentages.
A competitor may need to modify both architecture and composition to avoid all meaningful claim positions.

Vulnerabilities

Film coating with PVA, PEG, talc, and titanium dioxide is conventional technology.
The claims use broad numerical ranges.
The inventive distinction may depend on the specific combination of known coating materials and a known active ingredient.
Claims 1 and 6 use different percentage denominators, creating potential claim-construction disputes.
The phrase “about” introduces boundary uncertainty.
The claims do not require a demonstrated pharmacokinetic, stability, dissolution, or manufacturing advantage.
A well-designed alternative dosage form may avoid the claims without challenging validity.

The patent is strongest against literal copies of the claimed coated-core architecture. It is weaker as a barrier to alternative combination-tablet designs.

What prior-art issues are most relevant?

A validity review would likely focus on four prior-art categories:

Saxagliptin combination products

Earlier publications concerning saxagliptin combined with metformin, dapagliflozin, or other antidiabetic agents could establish the combination context but may not disclose the claimed coating sequence.

PVA film-coating systems

Prior art describing PVA as a seal coat, drug-containing film coat, or protective outer coat could be relevant to anticipation or obviousness.

Layered and press-coated tablets

References involving a preformed core tablet surrounded by multiple coating layers may be especially important. The analysis would need to compare:

The order of the layers;
The placement of saxagliptin;
The use of PVA in each layer;
The numerical ranges;
The identity of the second drug;
The presence of PEG, talc, titanium dioxide, plasticizer, glidant, and opacifier.

Combination dosage-form patents

Prior art involving multilayer tablets, coated tablets, and “tablet-in-tablet” systems may support an obviousness argument even if no single reference discloses every limitation.

The strongest invalidity case would require a reference, or a technically supportable combination of references, that addresses the unusual feature: saxagliptin in the intermediate coating surrounding a different drug tablet.

What manufacturing and intellectual-property barriers does the patent create?

The patent creates a manufacturing barrier for a specific process architecture. A manufacturer seeking to reproduce the commercial appearance or release behavior of a covered product may need to use:

Core-tablet compression;
Inner sealing;
Application of a saxagliptin-containing coating suspension;
Drying and weight-gain control;
Application of an outer protective film;
Layer-specific analytical testing.

The process may require controlled coating uniformity because saxagliptin is distributed over the tablet surface rather than compressed into the core. That can create scale-up and content-uniformity issues independent of patent rights.

The patent does not expressly claim the coating process itself. A manufacturer may therefore be able to use a different process to produce a noninfringing product, provided the resulting dosage form does not satisfy the composition claims.

Which companies are relevant to the patent landscape?

The principal commercial parties are:

Company	Relevance
AstraZeneca	Originator and principal commercial sponsor associated with saxagliptin products
Bristol-Myers Squibb	Historical development and commercialization partner for saxagliptin
Generic manufacturers	Potential ANDA applicants for saxagliptin and saxagliptin combinations
Contract manufacturers	Potential holders of process and formulation know-how, even where they are not patent owners

The commercial importance of the patent depends on whether the protected architecture is used in an approved product and whether the patent is listed against that product. Ownership, assignment, and licensing should be confirmed in the USPTO assignment database and the relevant FDA NDA records. [2]

What licensing deals and settlements affect U.S. 9,339,472?

A reliable licensing or settlement assessment requires a review of:

USPTO assignment records;
SEC filings;
FDA Paragraph IV litigation notices;
District court complaints and judgments;
ANDA settlement disclosures;
Company annual reports and transaction announcements.

The patent number alone does not establish a license, covenant not to sue, authorized-generic arrangement, or settlement. No licensing or settlement right should be inferred merely from commercial availability of a saxagliptin product.

What litigation status affects this patent?

The key litigation questions are:

Whether the patent was listed for an approved saxagliptin combination product;
Whether any ANDA applicant served a Paragraph IV notice;
Whether the patent holder filed an infringement action within the statutory period;
Whether the case was dismissed, settled, or adjudicated;
Whether any judgment addressed claim construction or validity;
Whether a terminal disclaimer or post-grant proceeding affects enforceability.

No litigation conclusion should be drawn solely from the patent’s issue number or from the existence of generic saxagliptin products. Patent litigation may target a different patent in the same estate, and a generic launch may occur after a settlement or license.

How does U.S. 9,339,472 compare with saxagliptin drug-substance patents?

U.S. 9,339,472 is narrower in subject matter but potentially more product-specific than core saxagliptin patents.

Patent category	Protected subject matter	Typical design-around
Saxagliptin compound patent	Active molecule and chemical genus	New chemical entity or salt strategy, if available
Saxagliptin salt patent	Specific salt or solid form	Alternative salt, polymorph, or formulation
Combination patent	Saxagliptin plus another active ingredient	Different combination or dosing regimen
Formulation patent	Layered dosage form and excipient composition	Different architecture or excipient system
Method-of-use patent	Treatment indication or patient population	Different indication or label strategy
Manufacturing patent	Synthesis or processing method	Alternative process

The patent at issue is a formulation-layer patent. It does not replace or necessarily overlap with patents covering saxagliptin synthesis, crystalline forms, therapeutic uses, or combination pharmacology.

What is the commercial exposure?

The exposure is greatest for a product that combines saxagliptin with another drug in a single coated tablet and uses the same multilayer film-coating approach. Exposure is lower for products using separate tablets, a conventional bilayer core, or a capsule.

Commercial exposure should be assessed against:

U.S. sales of saxagliptin combination products;
The product’s remaining patent and regulatory exclusivity;
The number of potential ANDA applicants;
Whether the patent is Orange Book-listed;
The availability of a noninfringing formulation;
The cost and timing of reformulation;
The likelihood of an authorized generic or settlement.

Saxagliptin product sales are not attributable to this patent unless the relevant product actually practices the claimed formulation and the patent is enforceable against that product.

Key Takeaways

U.S. 9,339,472 claims a multilayer coated combination tablet.
The core must contain a drug other than saxagliptin.
Saxagliptin must be in the intermediate coating layer.
PVA is required in the inner, intermediate, and outer coating layers.
Claims 1-5 use percentages based on the drug-tablet weight.
Claims 6-20 use percentages based largely on the relevant coating-layer weight.
Saxagliptin hydrochloride, PEG, talc, and titanium dioxide are covered by dependent claims.
Conventional single-core combination tablets and many bilayer designs may avoid literal infringement.
Orange Book listing, Paragraph IV exposure, licensing, and litigation cannot be established from the claims alone and must be confirmed in FDA, USPTO, court, and company records.
The patent is strongest against a direct copy of the claimed coated-core architecture and weaker against alternative dosage forms.

FAQs

Does U.S. 9,339,472 cover Kombiglyze XR?

It may be relevant to Kombiglyze XR because that product combines saxagliptin and metformin, but infringement and Orange Book relevance depend on the actual dosage-form architecture and patent listing for the applicable NDA.

Can a generic avoid the patent by placing saxagliptin in the tablet core?

Potentially. Claims 1 and 6 require saxagliptin in a second coating layer over a separate tablet core. A product placing saxagliptin in the core could present a stronger noninfringement position, subject to other patents.

Is saxagliptin hydrochloride the only salt covered?

No. The independent claims cover saxagliptin and pharmaceutically acceptable salts generally. Claims 2 and 7 specifically identify the hydrochloride salt.

Does the patent claim the coating process?

The supplied claims are product claims. They do not expressly claim the manufacturing steps used to apply the inner, saxagliptin-containing, and outer coating layers.

Can a product infringe without using the exact percentages in the examples?

Yes, if it falls within the numerical ranges of an asserted claim. The claims are not limited to the specific 40% PVA, 20% PEG, 15% talc, and 25% titanium dioxide embodiments in claims 13, 17, and 20.

References

U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
United States Patent and Trademark Office. (2016). U.S. Patent No. 9,339,472, Combination formulation. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Onglyza (saxagliptin) prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Kombiglyze XR (saxagliptin and metformin hydrochloride extended-release) prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Qtern (dapagliflozin and saxagliptin) prescribing information. FDA.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	049062	⤷ Start Trial
Argentina	099567	⤷ Start Trial
Australia	2005249467	⤷ Start Trial
Brazil	PI0510419	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,339,472