U.S. Patent 12,213,988: Dapagliflozin Chronic Kidney Disease Claims, Patent Scope and Market Risk

U.S. Patent No. 12,213,988 is a method-of-treatment patent directed to dapagliflozin use in chronic kidney disease patients who do not have type 2 diabetes. Its core protection covers once-daily dapagliflozin administered for at least four months to reduce kidney and cardiovascular outcomes. The patent also contains narrower claims covering defined eGFR and UACR ranges, background ACE inhibitor or ARB therapy, specified clinical hazard ratios, non-dialysis patients, and combination treatment with AZD9977.

The patent does not claim dapagliflozin as a chemical compound, a tablet formulation, or a manufacturing process. Its commercial value therefore depends on enforcement against use of dapagliflozin for the claimed non-diabetic CKD population and on the availability of generic labeling for that indication.

What does U.S. Patent 12,213,988 protect?

The independent claims create two principal claim groups.

Claim group	Core protected subject matter	Main limitations
Claims 1-7, 15-18, 23	Treatment of non-type-2-diabetic CKD patients	Once-daily dapagliflozin, at least four months, reduction of kidney and cardiovascular outcomes
Claims 8-14, 19-22, 24	Treatment of non-type-2-diabetic CKD patients based on a composite endpoint	At least 50% sustained eGFR decline, ESKD, or cardiovascular or renal death
Claims 15-22	Dapagliflozin plus AZD9977	AZD9977 dose of 15-150 mg daily; optional high hyperkalemia-risk population
Claims 23-24	Non-dialysis population	Patient is not receiving chronic dialysis

The independent claims are treatment-method claims. To fall within claim 1, a treatment generally must include:

A patient with chronic kidney disease at risk of progression.
No type 2 diabetes.
Once-daily dapagliflozin.
A dose and duration sufficient to reduce specified clinical risks.
Treatment for at least four months.

Claim 8 uses a separate composite endpoint. It focuses on reducing the risk of a first event consisting of approximately 50% sustained eGFR decline, progression to ESKD, or cardiovascular or renal death.

How do the claims map to the DAPA-CKD clinical population?

The patient-selection limitations closely track the DAPA-CKD trial population. DAPA-CKD enrolled patients with eGFR from 25 to 75 mL/min/1.73 m² and UACR from 200 to 5,000 mg/g. Participants generally received stable background renin-angiotensin system inhibition unless medically contraindicated. The trial included patients with and without type 2 diabetes and reported a hazard ratio of approximately 0.61 for the primary composite kidney and cardiovascular endpoint (Heerspink et al., 2020).

Patent limitation	DAPA-CKD alignment
eGFR 25-75 mL/min/1.73 m²	Matches the principal enrollment range
UACR 200-5,000 mg/g	Matches the principal enrollment range
ACE inhibitor or ARB background therapy	Matches trial treatment practice
No type 2 diabetes	Covers the non-diabetic subgroup
At least four months of therapy	Captures sustained treatment rather than a single prescription
50% eGFR decline, ESKD, or renal/CV death	Reflects the trial’s renal outcome framework
HR approximately 0.61	Tracks the reported primary outcome result

The claims therefore have a narrow clinical focus but a strong factual connection to the pivotal evidence supporting dapagliflozin in CKD.

What outcomes are protected by claims 1 and 8?

Claim 1 protects a broader outcome formulation. It refers to reducing the risk of:

Sustained eGFR decline;
ESKD;
Cardiovascular death; and
Hospitalization for heart failure.

Claim 2 narrows the eGFR component to a decline of at least 50%. Claim 3 defines ESKD through one or more of the following:

Sustained eGFR below 15 mL/min/1.73 m²;
Initiation of chronic dialysis; or
Renal transplantation.

Claim 8 uses a more structured composite endpoint: approximately 50% sustained eGFR decline, ESKD, or cardiovascular or renal death. Claims 9 and 10 further define ESKD and baseline kidney-function criteria.

The wording in claim 8 stating “˜50%” appears to be a typographical or formatting variation of “approximately 50%.” That wording can create claim-construction issues. A court would likely assess the specification, prosecution history, and technical meaning of the symbol before determining whether it means approximately 50%, at least 50%, or another threshold.

What dapagliflozin dose and treatment duration are covered?

The independent claims do not specify a numeric dapagliflozin dose. They require once-daily administration at a dose and duration sufficient to reduce the claimed risks. Claim 18 specifies 10 mg orally once daily for the claim 1 pathway. Claim 22 does the same for the claim 8 pathway.

Claim	Dapagliflozin requirement
1	Once daily; dose and duration sufficient for risk reduction; at least four months
8	Once daily; dose and duration sufficient for composite-endpoint risk reduction; at least four months
18	10 mg orally once daily
22	10 mg orally once daily

The four-month minimum is a meaningful limitation. A short prescription, isolated dose, or treatment course that ends before four months would not satisfy the express duration limitation, although a plaintiff could argue that an ongoing prescription is intended to continue beyond that period.

The phrase “sufficient to reduce the risk” creates a functional limitation. It does not necessarily require the treating physician to know that the individual patient will experience a benefit. It may instead require that the regimen be one capable of producing the claimed population-level clinical effect. The interpretation would depend on the patent specification and prosecution record.

What ACE inhibitor and ARB combinations are covered?

Claims 5-7 and 11-13 cover patients receiving specified background renin-angiotensin system therapy.

Category	Listed drugs
ACE inhibitors	Captopril, enalapril, lisinopril
ARBs	Valsartan, losartan, irbesartan

The claims cover either:

A patient who was receiving an ACE inhibitor or ARB before dapagliflozin treatment; or
A patient who receives the ACE inhibitor or ARB during dapagliflozin treatment.

This language extends beyond simultaneous administration. A patient with prior ACE inhibitor or ARB exposure may satisfy the first alternative even if the background drug is later discontinued, depending on claim construction and the temporal relationship established by the evidence.

The limitation narrows infringement risk for patients outside the trial-like background-therapy setting, while preserving a substantial commercial population because ACE inhibitors and ARBs are standard CKD treatments.

What AZD9977 combination treatment is protected?

Claims 15-22 add AZD9977 to the dapagliflozin regimen. AZD9977 is an investigational mineralocorticoid receptor pathway drug associated with AstraZeneca’s cardiorenal development programs. These claims require a pharmaceutical composition containing a therapeutically effective amount of AZD9977 or a pharmaceutically acceptable salt.

Claims 16 and 20 narrow the population to patients at high risk for hyperkalemia. Claims 17 and 21 specify an AZD9977 dose of 15-150 mg daily. Claims 18 and 22 specify dapagliflozin at 10 mg orally once daily.

These claims are commercially dependent on AZD9977 regulatory development. They are not practical barriers to ordinary generic dapagliflozin monotherapy unless a generic product is used together with AZD9977 in the claimed CKD population.

How strong is the patent estate based on the claim language?

The patent has several strengths:

It targets the non-diabetic CKD use that expanded dapagliflozin’s therapeutic market.
Its clinical criteria closely correspond to a major outcomes trial.
It includes both broad outcome language and narrower patient-selection claims.
It covers the 10 mg dose used in commercial practice.
It includes non-dialysis and combination-treatment fallback positions.

The principal vulnerabilities are claim construction and validity.

Functional treatment language

“Dose and duration sufficient to reduce risk” may be challenged as indefinite or insufficiently objective if the specification does not provide a workable standard for determining compliance. The same issue applies to “at risk of progression.”

Obviousness

Dapagliflozin was known before the relevant patent filings. The central validity question is whether the claimed use in non-type-2-diabetic CKD, for the stated duration and outcomes, would have been obvious in view of earlier SGLT2 inhibitor data, CKD treatment guidelines, and clinical trial disclosures. The DAPA-CKD results support patentability as evidence of a clinically meaningful result, but the prior-art record remains decisive.

Outcome-based limitations

Claims 8 and 14 require clinical outcomes or statistical relationships. Claims 14(c), 14(d), 14(h), and 14(i) recite approximate hazard ratios and confidence intervals. These provisions may be useful as narrow fallback claims, but they can complicate infringement proof because the relevant result may require aggregate clinical data rather than patient-level prescribing evidence.

Written description and enablement

The claims cover a broad CKD population but include defined eGFR and UACR boundaries. A validity challenge could examine whether the disclosure supports the full scope, including all combinations of kidney function, albuminuria, background therapy, diabetes status, and AZD9977 use.

What is the Orange Book status of U.S. Patent 12,213,988?

The claims supplied are eligible in subject matter for consideration as method-of-use patent claims associated with an approved dapagliflozin product, but the claim text alone does not establish whether Patent No. 12,213,988 is listed in the FDA Orange Book.

Orange Book listing depends on submission by the NDA holder and FDA acceptance under the applicable listing rules. FDA listing status is separate from patent validity and enforceability. A patent can be enforceable without being listed, and an Orange Book listing can be challenged or removed.

For generic applicants, a listed method-of-use patent may trigger a Paragraph IV certification or a section viii statement that the generic label will omit the patented use under the Hatch-Waxman framework (FDA, 2024; 21 U.S.C. § 355).

When does dapagliflozin lose exclusivity?

Dapagliflozin’s original compound and product exclusivity are separate from the term of the ’988 patent. The original Farxiga compound patent expired before the current CKD method-of-use patent landscape became commercially decisive. Generic dapagliflozin entry can therefore occur while later method-of-use claims remain in force.

The exact expiration date of Patent No. 12,213,988 cannot be calculated from the claims provided. It requires the patent’s earliest effective nonprovisional priority date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension. The statutory baseline is generally 20 years from the earliest effective U.S. nonprovisional filing date, subject to those adjustments (35 U.S.C. § 154).

Which companies are challenging dapagliflozin exclusivity?

Generic manufacturers can challenge dapagliflozin exclusivity through:

Paragraph IV certifications against listed patents;
Section viii carve-outs for unpatented indications;
Declaratory-judgment actions;
Non-infringement and invalidity defenses in patent litigation; and
Launch at risk after regulatory approval.

The supplied claims do not identify a specific Paragraph IV filer, ANDA number, district-court case, settlement agreement, or launch date. No company, litigation date, or settlement term should be attributed to the ’988 patent solely from the claim text.

A generic label that omits the non-diabetic CKD indication may reduce direct induced-infringement exposure. It does not eliminate all risk if the product is actively promoted for the patented use or if substantial evidence supports inducement.

What litigation and settlement risks affect generic launch?

The highest-risk scenario is a generic dapagliflozin product marketed for CKD with a label that includes the claimed non-diabetic population, 10 mg once-daily dose, or the relevant renal-outcome indication. The risk is lower for a label limited to non-patented indications, but actual prescribing and promotional conduct remain relevant.

Potential litigation issues include:

Issue	Relevance
Direct infringement	Physicians or providers administer dapagliflozin for the claimed method
Induced infringement	Generic manufacturer promotes or instructs use for non-diabetic CKD
Divided infringement	Multiple actors perform separate claim steps
Claim construction	Meaning of “sufficient,” “at risk,” “approximately,” and “nominally significant”
Validity	Obviousness, written description, enablement, and indefiniteness
Regulatory carve-out	Whether the approved generic label omits the patented CKD use
Settlement	Potential delayed entry, licensed entry, or no-agreement outcome

No settlement agreement or litigation status is established by the supplied information.

How does the ’988 patent compare with formulation and manufacturing patents?

The ’988 patent is weaker against ordinary product substitution than a composition or formulation patent because it does not claim:

Dapagliflozin’s chemical structure;
A specific tablet composition;
An extended-release dosage form;
A combination tablet;
A crystalline form;
A process for manufacturing dapagliflozin; or
Packaging or delivery technology.

Its value is concentrated in use enforcement. Formulation and manufacturing patents can block sale of a product regardless of indication. The ’988 patent instead requires proof that the product is used in a defined patient population and treatment setting.

What geographic coverage does the patent provide?

Patent No. 12,213,988 provides U.S. rights only. It does not directly block dapagliflozin use in Europe, Japan, Canada, China, or other markets. Foreign counterparts would require separate patent rights, different claim language, and country-specific validity and enforcement analysis.

The clinical evidence underlying the claims may support foreign patent families, but the existence, status, and expiration of those counterparts cannot be inferred from the U.S. claims.

What is the commercial exposure for Farxiga and generic dapagliflozin?

The patent is most relevant to the CKD portion of the dapagliflozin market, particularly patients without type 2 diabetes. Its revenue impact depends on four factors:

Whether the patent is listed in the Orange Book.
Whether generic labels include or omit the CKD indication.
Whether AstraZeneca enforces the patent against generic promotion or use.
Whether physicians prescribe generic dapagliflozin for the patented population despite a carve-out.

Because dapagliflozin is already used across diabetes, heart failure, and CKD, the patent does not protect all product sales. It protects a specific use segment.

Key Takeaways

U.S. Patent 12,213,988 is a method-of-treatment patent, not a compound, formulation, or manufacturing patent.
Its core population is non-type-2-diabetic CKD patients at risk of progression.
The main regimen is once-daily dapagliflozin for at least four months, with claim 18 and claim 22 specifying 10 mg orally once daily.
The patient-selection criteria mirror DAPA-CKD: eGFR of 25-75 mL/min/1.73 m² and UACR of 200-5,000 mg/g.
Claims 15-22 add AZD9977 and target patients at high risk for hyperkalemia.
Main legal vulnerabilities include obviousness, indefiniteness of functional terms, and proof of outcome-based limitations.
Generic entry may remain possible through a section viii carve-out, subject to label content and promotional conduct.
The claims alone do not establish Orange Book listing, Paragraph IV litigation, a settlement, licensing terms, or the patent’s precise expiration date.
Geographic protection is limited to the United States unless corresponding foreign patents exist.

FAQs

Does Patent 12,213,988 cover all dapagliflozin prescriptions?

No. It covers specified treatment of non-type-2-diabetic CKD patients, primarily once-daily treatment for at least four months and related renal or cardiovascular outcomes.

Does the patent cover dapagliflozin for type 2 diabetes?

No. The claims expressly require that the patient does not have type 2 diabetes.

Can a generic manufacturer sell dapagliflozin for diabetes while this patent remains in force?

Potentially yes, if the generic label and marketing omit the patented CKD use and the manufacturer does not induce that use.

Does AZD9977 make the patent a combination-product patent?

No. Claims 15-22 are combination-treatment method claims. They do not claim a fixed-dose dapagliflozin-AZD9977 pharmaceutical composition.

Is the 0.61 hazard ratio required for every infringement case?

No. The hazard-ratio limitations appear in dependent claim 14. The broader independent claims do not expressly require the 0.61 result, although they contain their own outcome and risk-reduction limitations.

References

AstraZeneca. (n.d.). U.S. Patent No. 12,213,988, claims 1-24. United States Patent and Trademark Office.

Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

Heerspink, H. J. L., Stefansson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F. F., Mann, J. F. E., McMurray, J. J. V., Lindberg, M., Rossing, P., Sjöström, C. D., Toto, R. D., Langkilde, A. M., & Wheeler, D. C. (2020). Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine, 383(15), 1436-1446. https://doi.org/10.1056/NEJMoa2024816

United States Code. (2024). 21 U.S.C. § 355. Abbreviated applications and patent certifications.

United States Code. (2024). 35 U.S.C. § 154. Contents and term of patent; provisional rights.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca Ab	FARXIGA	dapagliflozin	TABLET;ORAL	202293-002	Jan 8, 2014	AB	RX	Yes	Yes	12,213,988*PED	⤷ 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	121738	⤷ Start Trial
Australia	2021202643	⤷ Start Trial
Australia	2023202490	⤷ Start Trial
Australia	2025202409	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 12,213,988

Which drugs does patent 12,213,988 protect, and when does it expire?

Summary for Patent: 12,213,988