United States Patent 9,949,997: Empagliflozin Cardiovascular-Outcome Patent Scope, Expiration, and Generic Risk
United States Patent No. 9,949,997 protects methods of administering empagliflozin to patients with type 2 diabetes and cardiovascular disease to reduce cardiovascular death, hospitalization for heart failure, or all-cause mortality. The claims require oral empagliflozin at a total daily dose of 10 mg or 25 mg. The patent is a method-of-use patent, not a basic compound or tablet-composition patent.
The patent is associated with the Jardiance product marketed by Boehringer Ingelheim and Eli Lilly. Its principal commercial significance is the additional exclusivity it provides for the cardiovascular-outcome indication after the core empagliflozin compound patent expired.
What does United States Patent 9,949,997 cover?
Patent 9,949,997 covers three related treatment objectives:
| Claim group |
Protected outcome |
Required patient population |
Required dose |
| Claims 1, 2, 7-10 |
Reduced risk of cardiovascular death |
Type 2 diabetes and cardiovascular disease |
Oral 10 mg or 25 mg daily |
| Claims 3, 4, 11-14 |
Reduced risk of hospitalization for heart failure |
Type 2 diabetes and cardiovascular disease |
Oral 10 mg or 25 mg daily |
| Claims 5, 6, 15-18 |
Reduced risk of all-cause mortality |
Type 2 diabetes and cardiovascular disease |
Oral 10 mg or 25 mg daily |
The independent claims are claims 1, 3, and 5. Claims 2, 4, and 6 add administration through a pharmaceutical composition containing 10 mg or 25 mg of empagliflozin. Claims 7 through 18 separately narrow the dosing and composition limitations.
The patent does not broadly claim every use of empagliflozin. It requires the combination of:
- A patient with type 2 diabetes mellitus.
- Cardiovascular disease.
- Oral empagliflozin administration.
- A total daily dose of 10 mg or 25 mg.
- A reduction in one of the specified clinical outcomes.
A patient treated with empagliflozin for glycemic control who does not have cardiovascular disease would not satisfy the full combination of limitations in claims 1, 3, or 5.
How are the claims structured?
Independent claim 1: cardiovascular death
Claim 1 covers administering empagliflozin to a patient with type 2 diabetes and cardiovascular disease where the treatment reduces the risk of cardiovascular death. The dose must be 10 mg or 25 mg orally per day.
The claim does not require:
- A prior myocardial infarction.
- A prior stroke.
- Established coronary artery disease specifically.
- Heart failure at baseline.
- Renal impairment.
- A particular background diabetes therapy.
- A particular treatment duration.
- A specific formulation beyond oral administration.
The term “cardiovascular disease” is therefore important to infringement analysis. The claim is narrower than a claim covering all patients with type 2 diabetes but potentially broad across different forms of established cardiovascular disease.
Independent claim 3: hospitalization for heart failure
Claim 3 covers the same patient and dose conditions but defines the treatment result as a reduced risk of hospitalization for heart failure.
The claim does not expressly require that the patient already have a diagnosis of heart failure. It requires cardiovascular disease. This distinction matters because a patient with established atherosclerotic cardiovascular disease but no diagnosed heart failure may fall within the wording of the claim if the other limitations are met.
Independent claim 5: all-cause mortality
Claim 5 covers treatment that reduces the risk of death from any cause. It uses the same type 2 diabetes, cardiovascular disease, oral administration, and 10 mg or 25 mg daily-dose limitations.
This is the broadest outcome category in the patent from a mortality standpoint, but the patient-population limitation remains material. The claim is not a general all-cause-mortality claim for every empagliflozin user.
What do the dependent claims add?
Claims 2, 4, and 6 specify administration as a pharmaceutical composition containing 10 mg or 25 mg of empagliflozin. Claims 9, 10, 13, 14, 17, and 18 then select either the 10 mg or 25 mg composition.
Claims 7, 11, and 15 limit administration to 10 mg daily. Claims 8, 12, and 16 limit administration to 25 mg daily.
The dependent claims create multiple overlapping routes to infringement:
- A patient receiving one 10 mg tablet daily.
- A patient receiving one 25 mg tablet daily.
- A regimen using another oral composition that delivers a total daily dose of 10 mg or 25 mg.
- A product containing 10 mg or 25 mg in the administered pharmaceutical composition.
The claims do not require the branded Jardiance tablet, a particular excipient, a particular release profile, or a particular tablet shape. A pharmaceutically equivalent generic product could therefore fall within the literal scope if it is marketed or used for the claimed patient population and outcomes.
When does Patent 9,949,997 expire?
Patent 9,949,997 has an expiration date of September 1, 2034, based on the patent term reflected in public patent and FDA listing records. The patent was granted on April 24, 2018. Its relevant priority chain traces to an application filed in 2014, making September 1, 2034 the operative term endpoint for commercial planning unless a later adjustment or extension applies.[1][2]
| Event |
Date |
| Earliest relevant priority date |
September 1, 2014 |
| U.S. patent grant |
April 24, 2018 |
| Patent number |
US 9,949,997 |
| Listed product association |
Jardiance, empagliflozin |
| Listed expiration |
September 1, 2034 |
The patent term is materially later than the core empagliflozin compound patent, U.S. Patent No. 8,067,477, which expired in 2025 absent a further applicable extension.[3] This creates a secondary-patent barrier focused on cardiovascular outcomes rather than the active pharmaceutical ingredient itself.
What is the Orange Book status of Patent 9,949,997?
Patent 9,949,997 is listed in the FDA Orange Book for Jardiance-related method-of-use protection. The listing identifies a use involving cardiovascular risk reduction in patients with type 2 diabetes and cardiovascular disease.[2]
The Orange Book listing matters because an abbreviated new drug application applicant referencing Jardiance must address listed patents through one of four certifications:
- Paragraph I: no patent information has been submitted.
- Paragraph II: the patent has expired.
- Paragraph III: the applicant will wait until patent expiration.
- Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.
For a generic seeking approval before September 1, 2034, Patent 9,949,997 is a potential Paragraph IV target. The applicant could also seek a section viii labeling carve-out for the patented cardiovascular uses, provided the remaining label can support approval under FDA requirements.[4]
How strong is the patent estate for Jardiance cardiovascular uses?
The patent estate is strongest where the proposed generic label, promotional materials, or prescribing information expressly includes the cardiovascular-outcome indications covered by the claims.
Its principal strengths are:
- The claims track clinically meaningful outcomes recognized by FDA labeling.
- The dose limitations match the commercial Jardiance strengths.
- The patient population is commercially important.
- The claims cover both cardiovascular mortality and heart-failure hospitalization.
- The claims include composition-specific dependent claims that correspond to ordinary tablet administration.
- The patent has a term extending well beyond the core compound patent.
Its principal limitations are:
- It is a method-of-use patent rather than a compound patent.
- It does not cover every empagliflozin prescription.
- It requires type 2 diabetes and cardiovascular disease together.
- It requires 10 mg or 25 mg per day.
- The “risk reduction” language may require proof that the accused use is directed to the claimed clinical objective.
- A generic may attempt to omit the patented indications from its label.
The practical strength is therefore high for an on-label cardiovascular indication and lower for a diabetes-only label that omits cardiovascular risk reduction.
What generic entry risks exist after the basic empagliflozin patent expires?
Expiration of the core compound patent does not automatically eliminate infringement risk under Patent 9,949,997. A generic manufacturer could obtain approval for non-protected indications while remaining exposed if it markets the product for the patented uses.
A generic launch strategy would generally fall into three categories:
| Launch strategy |
Patent exposure |
Commercial effect |
| Wait for September 1, 2034 |
Lowest patent risk |
Delayed full-label competition |
| Paragraph IV challenge |
Litigation and possible at-risk launch |
Earlier entry if successful or settled |
| Section viii carve-out |
Lower method-of-use exposure |
Reduced label scope and potential market limitation |
A section viii strategy can be commercially difficult because physicians may prescribe the generic for the same patients treated under the branded cardiovascular indication. Product labeling, pharmacy substitution, medical education, payer materials, and sales activity would be examined in an induced-infringement dispute.
The branded manufacturer could argue that the generic’s label, distribution strategy, or promotional conduct encourages use for cardiovascular risk reduction even if express wording is removed. The generic would likely argue that approval for non-infringing uses does not establish inducement.
What Paragraph IV challenges affect Patent 9,949,997?
The relevant Paragraph IV issue is whether an ANDA applicant can challenge the patent as invalid, unenforceable, or not infringed while seeking approval before September 1, 2034.
The most likely legal theories include:
Invalidity based on obviousness
An ANDA applicant could argue that the claimed use was obvious in view of:
- Earlier empagliflozin diabetes studies.
- SGLT2 inhibitor cardiovascular data.
- Cardiovascular-outcome evidence for other sodium-glucose cotransporter-2 inhibitors.
- Known cardiovascular benefits associated with glucose-lowering or natriuretic therapies.
- Clinical trial protocols or publications suggesting cardiovascular benefit.
The patent holder would respond that the specific reduction in cardiovascular death, heart-failure hospitalization, and all-cause mortality in the defined population was not predictable before the relevant filing date.
Written description and enablement
A challenger could argue that the specification did not adequately support all claimed outcomes across the full patient population and both approved doses. The patent holder would rely on the clinical evidence and disclosure supporting the claimed outcome reductions.
Infringement and label carve-out
The most commercially important defense is non-infringement. A generic applicant could omit the cardiovascular indication and argue that its label does not instruct users to practice the patented methods.
The response would focus on whether the remaining label necessarily encourages use in patients with cardiovascular disease, and whether the generic’s conduct outside the label creates induced infringement.
What clinical and FDA milestones support the patent?
The claims are closely tied to the EMPA-REG OUTCOME clinical program. That trial evaluated empagliflozin in patients with type 2 diabetes and established cardiovascular disease. The study reported reductions in cardiovascular death, all-cause mortality, and hospitalization for heart failure compared with placebo.[5]
The FDA approved Jardiance in 2014 for glycemic control in adults with type 2 diabetes. In 2016, FDA approved an expanded indication to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.[6]
These regulatory milestones align with the three independent claim groups, although the FDA label and patent claims should be compared separately. FDA approval does not itself establish patent validity or infringement. It does, however, increase the commercial importance of the claimed uses and the likelihood that generic labeling will be evaluated against the listed method-of-use patent.
What formulation patents are relevant to empagliflozin?
Patent 9,949,997 is not primarily a formulation patent. Its formulation limitations appear in dependent claims 2, 4, and 6 and require a pharmaceutical composition containing 10 mg or 25 mg of empagliflozin. Those claims do not identify a distinctive excipient system, coating, dissolution profile, or manufacturing process.
Separate Jardiance patent families may cover:
- The empagliflozin compound.
- Solid oral dosage forms.
- Combinations of empagliflozin with metformin.
- Fixed-dose combinations with linagliptin.
- Processes for preparing empagliflozin.
- Additional heart-failure and chronic-kidney-disease uses.
The commercial impact of those families depends on their individual Orange Book listings, claim scope, and expiration dates. Patent 9,949,997 should not be treated as a substitute for a full Jardiance patent-family review.
What manufacturing and intellectual-property barriers remain?
After compound-patent expiration, manufacturing entry is generally less difficult than before because the active ingredient can be produced by multiple suppliers. The remaining barriers are more likely to involve:
- Regulatory approval of the finished dosage form.
- Bioequivalence.
- Polymorph and solid-state control.
- Process know-how.
- Combination-product development.
- Method-of-use labeling.
- Orange Book litigation.
- Supply contracts and commercial scale-up.
Patent 9,949,997 does not prevent manufacture of empagliflozin for every use. It can, however, raise litigation risk for a manufacturer whose commercial plan includes the cardiovascular-benefit market.
How does Patent 9,949,997 compare with the core empagliflozin patent?
| Issue |
US 8,067,477 |
US 9,949,997 |
| Principal protection |
Empagliflozin compound and related use |
Cardiovascular-outcome treatment methods |
| Patent type |
Foundational active-ingredient protection |
Secondary method-of-use protection |
| Product dependence |
Broadly tied to empagliflozin |
Tied to defined patients, outcomes, and doses |
| Commercial scope |
Broad molecule-level barrier |
Narrower but commercially targeted indication |
| Expiration |
2025 |
September 1, 2034 |
| Generic design-around |
Difficult before expiry |
Possible through label carve-out or non-covered use |
| Main litigation issue |
Compound and product infringement |
Induced infringement and indication carve-out |
The 9,949,997 patent extends protection for a commercially important use after loss of basic molecule exclusivity. Its value is concentrated in the cardiovascular-risk segment rather than the entire diabetes market.
What licensing deals and companies are associated with empagliflozin?
Boehringer Ingelheim and Eli Lilly developed and commercialized Jardiance through their diabetes alliance. Boehringer Ingelheim is the principal patent and regulatory entity associated with Jardiance in the United States, while Eli Lilly is the co-commercialization partner.[7]
The alliance is commercially relevant because patent enforcement, regulatory strategy, and settlement negotiations may involve both companies even when a particular patent is formally assigned to or listed by one entity.
What patent litigation affects Jardiance and empagliflozin?
Jardiance has been subject to the standard ANDA patent-risk cycle associated with an aging branded product: generic applicants may challenge the core compound patent, formulation or combination patents, and method-of-use patents.
For Patent 9,949,997, the decisive litigation questions are likely to be:
- Whether the ANDA label includes the cardiovascular uses.
- Whether a section viii carve-out is accepted by FDA.
- Whether the patent claims are invalid for obviousness or inadequate disclosure.
- Whether the generic’s marketing induces use for the patented outcomes.
- Whether any settlement permits an agreed launch date before September 1, 2034.
A final invalidity judgment or enforceability ruling would materially change the value of the patent. In the absence of such a ruling, the patent remains an active Orange Book-listed barrier to an unrestricted cardiovascular-use generic launch.
Key Takeaways
- US 9,949,997 covers empagliflozin treatment methods for reducing cardiovascular death, heart-failure hospitalization, and all-cause mortality.
- The claims require type 2 diabetes, cardiovascular disease, oral empagliflozin, and a 10 mg or 25 mg total daily dose.
- The patent expires September 1, 2034, according to public patent and Orange Book records.
- It is a method-of-use patent, not a foundational compound patent.
- Its strongest commercial protection applies to an unrestricted generic label that includes cardiovascular benefits.
- A section viii carve-out or Paragraph IV challenge may provide an earlier generic-entry route.
- The patent is more vulnerable to label-based design-around arguments than a compound patent.
- The Jardiance patent estate also includes separate compound, formulation, combination, manufacturing, heart-failure, and chronic-kidney-disease families that require separate analysis.
- The Boehringer Ingelheim-Eli Lilly alliance remains the key commercial relationship associated with Jardiance.
FAQs About US Patent 9,949,997 and Jardiance Exclusivity
Can a generic empagliflozin product launch before September 1, 2034?
It may be possible through a successful Paragraph IV challenge, a settlement-authorized launch, or an FDA-approved label that omits the patented cardiovascular uses. An unrestricted label would face greater infringement risk.
Does Patent 9,949,997 cover Jardiance for ordinary blood-glucose control?
No. The claims require cardiovascular disease and one of the specified cardiovascular or mortality outcomes. Diabetes-only use is outside the complete claim combination.
Does the patent cover 5 mg empagliflozin?
No. The claims specify a total daily amount of 10 mg or 25 mg. A 5 mg regimen would not literally satisfy the stated dose limitation.
Does the patent cover empagliflozin-metformin combination products?
Not necessarily. A combination product could fall within the claims if it delivers the required empagliflozin dose to the claimed patient population for a claimed outcome. Separate combination-product patents may also apply.
Is a biosimilar challenge relevant to empagliflozin?
No. Empagliflozin is a small-molecule active ingredient. The relevant pathway is an ANDA generic-drug challenge, not a biosimilar application under the Public Health Service Act.
References
- United States Patent and Trademark Office. (2018). U.S. Patent No. 9,949,997, methods of reducing cardiovascular risk with empagliflozin.
- U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- United States Patent and Trademark Office. (2012). U.S. Patent No. 8,067,477, empagliflozin and related compounds.
- U.S. Food and Drug Administration. (2017). Applications covered by patents and exclusivity.
- Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Inzucchi, S. E. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, 373(22), 2117-2128.
- U.S. Food and Drug Administration. (2016). FDA approves Jardiance to reduce cardiovascular death in adults with type 2 diabetes.
- Boehringer Ingelheim & Eli Lilly and Company. (2014). Jardiance prescribing information.
