Executive summary US Drug Patent 12,472,194 is directed to methods of treating and/or preventing HFpEF in non-diabetic humans with structural heart disease using a compound of Formula (I) (and prodrugs) with tight eligibility screens based on BMI <50 kg/m², HbA1c <5.7%, defined HFpEF-associated comorbid phenotypes, and detailed exclusion criteria (recent IV HF therapy, recent SGLT2 use, renal function, BP thresholds, recent CV events, and major alternative HF causes). The claims are structured to capture: (i) the patient population (non-diabetic, structural disease, biomarker thresholds), (ii) the indication/clinical endpoints (CV death, HF hospitalization, urgent HF, QoL instruments), and (iii) trial-like stability filters (timing windows and comorbidity exclusions). This is a method-of-treatment patent set with broad disease coverage but narrower patient gating, increasing enforceability against “same drug + same screened phenotype” generic/label-lean entrants while leaving room for design-around via different responder populations, different glycemic-status cutoffs, or different endpoint framing.

What is the scope of U.S. Patent 12,472,194 claims for HFpEF treatment?

Core claim coverage (Claim 1). The patent covers a method of treating and/or preventing HFpEF (and/or “at least one disease…associated therewith”) by administering a therapeutically effective amount of at least one Formula (I) compound and prodrugs to a non-diabetic human patient with structural heart disease, under the following defining constraints:

Non-diabetic eligibility
- BMI <50 kg/m²
- Hemoglobin A1c <5.7%
Disease scope
- HFpEF
- HFpEF-associated conditions specifically enumerated in Claim 1:
  - skeletal muscle dysfunction
  - vascular dysfunction
  - hypertension
  - pulmonary hypertension
  - renal failure
  - anemia
  - atrial fibrillation
  - major adverse cardiovascular events (MACE)
Structural heart disease requirement
- Structural heart disease is later tied to objective echo criteria in dependent claims (Claims 8–10).

What the claim does not explicitly cover

It does not claim a standalone composition product in Claim 1; the composition is framed as the pharmaceutical formulation containing Formula (I).
It does not claim diabetic patients as a category; Claim 1 is gated by HbA1c and “non-diabetic.”

Claim structure and how it changes scope

Dependent claims expand scope by:
- narrowing to treating HFpEF (Claim 2)
- adding combination therapy (Claim 3)
- specifying MACE constituents and hospitalization subtypes (Claims 4–5)
- expanding inclusion criteria by age, symptomatic HF history, NYHA class, duration, diuretic exposure, and NT-proBNP thresholds (Claim 6)
- defining objective HF signs/symptoms and measurement thresholds (Claim 7)
- tightening structural heart disease phenotypes (Claims 8–10)
- adding extensive exclusion criteria (Claim 11) and an “all conditions” narrowing version (Claim 12)
- gating by LVEF bands (Claims 13–15)
- adding outcome-based efficacy statements (Claims 16–25, 30)
- adding functional and health status endpoints (Claims 21, 25, 26)
- adding physiologic endpoints (Claims 27–29)
- combination with standard of care (Claims 31–33)

Practical enforcement consequence

A method infringement theory is likely to track the patient screening logic. If a generic or alternative label targets a different population (diabetic; HbA1c cutoffs; BMI upper bound; LVEF band outside 40–49/≥50/≥45 definitions; different structural disease criteria; different endpoint scheme), the claim mapping weakens.

Which patient eligibility criteria are built into U.S. Patent 12,472,194?

Non-diabetic gate: how tight is it?

Claim 1 requires:

BMI <50 kg/m²
HbA1c <5.7%
“non-diabetic human patient”

Dependent claim language later compounds exclusion logic (Claim 11), but the HbA1c cutoff is the primary glycemic-status discriminator.

HFpEF population enrichment: what inclusion filters exist?

Claim 6 offers multiple alternate inclusion routes. The method covers a patient satisfying at least one:

age ≥40
documented symptomatic HF (NYHA II-IV) before treatment
symptoms/signs for ≥6 weeks with at least intermittent need for diuretic
NT-proBNP thresholds:
- NT-proBNP ≥300 μg/ml (without ongoing AF/flutter)
- NT-proBNP ≥600 μg/ml (with ongoing AF/flutter)

Objective structural heart disease: echo and dimension thresholds

Claim 8 defines structural heart disease as:

LV hypertrophy and/or LA enlargement.

Claim 9 defines LV hypertrophy:

septal thickness or posterior wall thickness ≥1.1 cm

Claim 10 defines LA enlargement via one or more measures:

LA width (diameter) ≥3.8 cm
LA length >5.0 cm
LA area ≥20 cm²
LA volume ≥55 mL
LA volume index ≥29 mL/m²

This materially narrows the structural heart disease requirement to quantifiable measurements, aiding claim charting.

LVEF windows: what does the patent say HFpEF means here?

Dependent claims carve out:

Claim 13: LVEF ≥45%
Claim 14: LVEF ≥50%
Claim 15: LVEF 40–49% (about 40 to about 49)

Even though HFpEF is typically LVEF-preserved, the patent expressly claims multiple bands, which can support flexibility in clinical program targeting while still remaining within a defined LVEF universe.

Clinical sign/symptom list

Claim 7 enumerates signs/symptoms including dyspnea/orthopnea/PND, reduced exercise tolerance, fatigue, edema, JVP, hepatomegaly/ascites, respiratory findings, tachycardia/irregular pulse, Cheyne-Stokes, and others. The claim is broad because it says the symptom/sign is “chosen from” the list.

How do the exclusion criteria in Claim 11 limit the protected method?

Claim 11 contains a long exclusion bundle. The method is for patients who do not have these conditions. Key categories:

Recent therapy exclusions

no IV HF therapy including diuretics for at least 12 hours
no SGLT2 inhibitor within 4 weeks

Renal and BP stability exclusions

no eGFR <25 mL/min/1.73 m²
systolic BP not <95 mmHg on two consecutive measurements 5 minutes apart
systolic BP not too high depending on baseline therapy:
- if not on ≥3 BP-lowering meds: no systolic BP ≥160 mmHg on two consecutive measurements
- or if ≥180 mmHg irrespective of treatment: excluded on two consecutive measurements

Recent CV events and planned procedures

Excluded if within 12 weeks prior:

myocardial infarction
unstable angina
coronary revascularization
ablation of atrial flutter/fibrillation
valve repair/replacement Also excludes planned coronary revascularization or planned ablations or valve repair/replacement.

Recent stroke/TIA

no stroke or TIA within 12 weeks

Alternative/concomitant diagnoses

no “probable alternative or concomitant diagnoses” accounting for HF symptoms in the treating physician’s opinion

Primary pulmonary causes

no primary pulmonary hypertension, chronic pulmonary embolism, or severe pulmonary disease

Other structural/cardiomyopathy etiologies

no infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, tamponade
no genetic HCM or obstructive HCM
no arrhythmogenic right ventricular cardiomyopathy/dysplasia
no uncorrected primary valvular disease

Prognosis and malignancy

no life expectancy <2 years due to non-cardiovascular condition
no active malignancy requiring treatment except basal/squamous skin cancers

Severe hepatic impairment

no acute/chronic liver disease with severe impairment

Claim 12 tightens further: the patient must satisfy each condition (a) through (n) in Claim 11.

Enforcement implication: If an accused use targets patients with recent MI/stroke, recent diuretic/IV therapy, or SGLT2 exposure, infringement of Claim 1 is still possible unless the claims require Claim 11 gating. But Claims 11 and 12 create a protected “trial-optimized” use profile.

What endpoints and patient reported outcomes are claimed (efficacy scope)?

Several dependent claims recite comparative efficacy “compared to placebo” and also specify measured instruments.

Clinical endpoints (comparative to placebo)

Claim 16: reduces CV death
Claim 17: reduces HF hospitalization
Claim 18: reduces urgent HF visit
Claim 19: reduces total HF hospitalizations and CV death
Claim 20: total hospitalizations include first and/or recurrent hospitalizations
Claim 23: reduces death from any cause
Claim 24: reduces hospitalization from any cause

Patient-reported outcomes and QoL tools

Claim 21: improves KCCQ (one or more of patient reported outcomes)
Claim 25: improves health status via EQ-5D-5L
Claim 26: improves health status via PGIS
Claim 30: improves KCCQ summary score, overall summary score, TSS, and/or QoL score

Physiologic endpoints

Claim 27: improves systolic BP
Claim 28: improves body weight
Claim 29: does not reduce eGFR (from baseline)

Litigation utility: Endpoint-based method claims can be used to anchor infringement in clinical evidence (trial results, post-marketing outcomes) and strengthen damages arguments if an accused product is marketed/used in line with those endpoints.

How is combination therapy handled in U.S. Patent 12,472,194?

Two dependent structures matter:

General add-on therapy (Claim 3)
- pharmaceutical composition further comprises at least one other therapeutic agent.
Standard of care contextualization (Claims 31–33)
- Claim 31: method comprises administration in addition to standard of care therapy.
- Claim 32: standard of care comprises treatments to control comorbidities and/or reduce composite of CV death and heart failure events.
- Claim 33: heart failure events are hospitalization for HF and/or urgent HF visits.

Enforcement consequence: The patent is built to avoid straightforward non-infringement arguments that an accused regimen differs only by adding other agents. It also anticipates the standard HF background of diuretics and guideline care, at least within the exclusion constraints.

What is covered under “major adverse cardiovascular events” in the claim set?

Claim 4 narrows “major adverse cardiovascular event” to:

myocardial infarction
stroke
cardiovascular death
cardiovascular hospitalization

Claim 5 further defines cardiovascular hospitalization as related to:

unstable or stable angina pectoris
heart failure
coronary revascularization

This supports a mapping between HFpEF event reduction and broader cardiovascular risk reduction, but still within the HFpEF method frame.

What does the claim set imply about the underlying Formula (I) compound strategy?

The claim text does not include the chemical identity of Formula (I), so direct claim-to-structure analysis is limited to scope mechanics. However, the patent is drafted to cover:

at least one Formula (I) compound
prodrugs thereof
a therapeutically effective amount for HFpEF prevention/treatment
administration to non-diabetic structural heart disease patients

From an IP strategy standpoint, this suggests the core value is the indication plus patient-phenotype selection, not only the chemical moiety. That makes label and clinical practice alignment central to enforceability.

How strong is the patent estate implied by this single claim set?

Based only on the claim text provided, the strongest aspects are:

Hard, measurable eligibility gates (HbA1c <5.7%, BMI <50, NT-proBNP thresholds, echo dimensions, LVEF ranges)
Large, detailed exclusion list (timing from IV diuretics, SGLT2 washout, recent MI/stroke/procedures, alternative diagnoses, pulmonary causes, infiltrative/constrictive etiologies)
Multiple dependent claims on endpoints and QoL (KCCQ, EQ-5D-5L, PGIS; CV death/HF hospitalization/urgent visits)
Combination and standard-of-care framing that reduces “different regimen” escape routes

The primary vulnerability, as drafted, is that the method is tethered to a very specific patient subpopulation and specific parameter thresholds. If an accused product is used in:

diabetic populations,
patients with HbA1c above 5.7%,
patients outside the structural echo criteria,
patients with recent IV HF therapy within 12 hours or SGLT2 within 4 weeks,
patients with recent MI/stroke/revascularization/valve events inside 12 weeks, then the claim mapping to dependent claims (Claims 11–12 and structural definitions) weakens.

What generic entry risks exist for competing HFpEF therapies under this patent?

Risk is highest when:

the competitor’s product is the same active (or a legally substituted equivalent) and
clinical use targets non-diabetic, structural heart disease HFpEF patients with the thresholds and exclusions described.

Risk decreases when:

clinical programs target broader HF populations without these biomarker cutoffs,
diabetic HFpEF populations are included,
different LVEF inclusion ranges are emphasized such that the exact dependent LVEF claims are not satisfied,
washout windows or inclusion logic differ materially from the Claim 11 exclusion list.

Because this is method-of-treatment language, “label carve-outs” and “population targeting” can become litigation leverage even when the active ingredient overlaps.

Orange Book status, FDA pathway, and Paragraph IV litigation: what can be concluded from the provided record?

No Orange Book entries, NDA/BLA references, patent listing history, FDA approval pathway, or litigation docket information are provided in the prompt. Without those, no accurate statement can be made about:

whether 12,472,194 is listed in the Orange Book,
any specific FDA label language that corresponds to the claim elements,
whether any Paragraph IV or district court cases are tied to this patent.

No such content is included here.

Timeline and claim landscape summary tied to the method’s gating logic

Below is a structured view of the “gate then measure” architecture embedded in the claims:

Layer	Claim(s)	Gate/Definition	Practical role in infringement
Glycemic status	1	non-diabetic; HbA1c <5.7%	narrows to non-diabetic phenotype
Body size	1	BMI <50 kg/m²	narrows inclusion
HF diagnosis frame	1, 2	HFpEF; treatment/prevention	anchors indication
Structural disease	8–10	LVH (septal/posterior ≥1.1 cm) and/or LA enlargement (width ≥3.8 cm etc.)	ties to objective echo thresholds
HF severity enrichment	6–7	age/NYHA II-IV/6+ weeks with diuretic/NT-proBNP thresholds; symptom list	supports clinical trial-like selection
Stability exclusions	11–12	IV HF therapy window; SGLT2 washout; eGFR/BP windows; recent CV events/stroke; alternative diagnosis; pulmonary/other cardiomyopathy etiologies; prognosis/malignancy/hepatic exclusions	creates a “clean” treated cohort
LVEF bands	13–15	≥45%, ≥50%, or 40–49%	adds additional dependent coverage hooks
Outcomes	16–20, 23–24, 21, 25–26, 30	CV death, HF hospitalization, urgent visits, any-cause death, QoL tools, KCCQ, EQ-5D-5L/PGIS	enables results-based infringement theories
Background therapy	3, 31–33	combination therapy and standard of care context	reduces avoidance via co-therapy

Key Takeaways

U.S. Patent 12,472,194 protects a method of treating and/or preventing HFpEF with Formula (I) compounds and prodrugs in a non-diabetic patient population defined by HbA1c <5.7% and BMI <50 kg/m² plus structural heart disease.
The claims are drafted with clinical-trial grade selection and exclusion logic (including SGLT2 washout, recent IV HF therapy window, BP/eGFR thresholds, 12-week CV event exclusions, and detailed cardiopulmonary differential diagnosis constraints).
Dependent claims broaden enforceability by adding echo-defined structural thresholds, LVEF band definitions, and endpoint claims tied to CV death, HF hospitalization, urgent HF, all-cause outcomes, and PRO/QoL instruments (KCCQ, EQ-5D-5L, PGIS).
Combination therapy and standard of care are incorporated, making “co-administered regimen” a weaker non-infringement pathway.
Design-around is most plausible through population selection deviations (diabetes/HbA1c; echo structural criteria; timing washouts; excluded recent CV events) rather than through minor formulation changes.

FAQs

1. What is the main patient eligibility trigger in U.S. Patent 12,472,194?
The method is for non-diabetic humans with structural heart disease, specifically requiring HbA1c <5.7% and BMI <50 kg/m².

2. How does the patent define structural heart disease for HFpEF?
It requires LV hypertrophy (septal/posterior wall thickness ≥1.1 cm) and/or left atrial enlargement (e.g., width ≥3.8 cm, volume ≥55 mL, or volume index ≥29 mL/m²).

3. What washout and timing exclusions could reduce infringement risk?
Patients with IV HF therapy (including diuretics) within 12 hours, or SGLT2 inhibitor within 4 weeks, or major CV events/procedures within 12 weeks fall outside key dependent claim gating.

4. Does the patent cover HFpEF patients across multiple LVEF ranges?
Yes. Dependent claims cover LVEF ≥45%, LVEF ≥50%, and LVEF about 40–49%.

5. What patient-reported outcome instruments are referenced in the claims?
The patent references KCCQ, EQ-5D-5L, and PGIS.

References

No external sources were cited because none were provided beyond the claim text in the prompt.

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	12,472,194*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
Australia	2019304032	⤷ Start Trial
Australia	2022201294	⤷ Start Trial
Australia	2024201641	⤷ Start Trial
Australia	2025279598	⤷ Start Trial
Brazil	112021000139	⤷ Start Trial
Canada	3105626	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 12,472,194

Which drugs does patent 12,472,194 protect, and when does it expire?

Summary for Patent: 12,472,194