United States Patent 10,500,247: Claim Scope, Angiotensin II Exclusivity, and Patent Landscape
U.S. Patent No. 10,500,247 protects dose-regimen methods for treating low blood pressure in patients with acute kidney injury, refractory hypotension, or severe hypotension using angiotensin II. The core limitation is an initial infusion rate of approximately 5 to 20 ng/kg/min. Several claims add upward titration, maximum doses of approximately 30 or 40 ng/kg/min, treatment duration, and human angiotensin II.
The patent is primarily a method-of-use and dosing patent. It does not, based on the supplied claims, claim the angiotensin II molecule, a formulation, a manufacturing process, or a delivery device.
What does U.S. Patent 10,500,247 claim?
The patent has two principal independent claims.
| Claim |
Core subject matter |
Additional limitations |
| 1 |
Treating low blood pressure in a human patient with AKI, refractory hypotension, or severe hypotension by administering angiotensin II at an initial rate of about 5 to 20 ng/kg/min |
None beyond the patient population and initial dose |
| 10 |
Same treatment method and initial dose range |
Upward titration and administration for about 0.25 to 120 hours |
Claims 2 through 9 depend from claim 1. Claims 11 through 18 depend from claim 10. Claims 19 through 22 add titration or duration limitations to the 10 to 20 ng/kg/min range in claim 5.
The claim set creates multiple overlapping protection positions rather than 22 materially distinct inventive concepts.
How broad is the independent claim covering angiotensin II dosing?
Claim 1 is broad within a defined clinical and dosing envelope. A potentially infringing method must include each of the following elements:
- A human patient.
- Low blood pressure.
- Acute kidney injury, refractory hypotension, or severe hypotension.
- Administration of angiotensin II.
- An initial administration rate from about 5 to about 20 ng/kg/min.
The claim does not require:
- A particular blood-pressure target.
- A particular vasopressor background regimen.
- A specific formulation or concentration.
- A particular infusion pump.
- A specified route beyond administration consistent with the claimed dosing method.
- A particular duration.
- Upward titration.
- A specific clinical outcome, such as reduced mortality or improved renal recovery.
The absence of a titration or duration limitation makes claim 1 the principal enforcement claim. A method that starts at 5, 10, 15, or 20 ng/kg/min can fall within its literal scope if the patient and disease-state limitations are satisfied.
Which dependent claims create meaningful additional coverage?
Claims 2, 3, and 4 separately recite initial rates of approximately 5, 10, and 20 ng/kg/min. These claims narrow the range but may provide useful fallback positions if the broader range in claim 1 is challenged.
Claim 5 covers an initial rate of approximately 10 to 20 ng/kg/min. It overlaps claims 3 and 4 and the upper half of claim 1.
Claims 6 through 8 cover upward titration, with claims 7 and 8 specifying titration to approximately 30 and 40 ng/kg/min. These claims target a treatment protocol rather than a single initial dose.
Claim 9 covers administration for approximately 0.25 to 120 hours. The range is unusually broad. It reaches treatment periods from approximately 15 minutes through five days.
Claim 10 combines three limitations:
- An initial rate of approximately 5 to 20 ng/kg/min.
- Upward titration.
- Administration for approximately 0.25 to 120 hours.
Claims 11 through 16 specify the initial dose and titration endpoints under claim 10. Claims 17 and 18 specify human angiotensin II. Claims 19 through 22 provide additional combinations involving the 10 to 20 ng/kg/min starting range.
What is the practical infringement risk for a generic or 505(b)(2) product?
The principal risk arises when a competing product label instructs clinicians to use angiotensin II in the claimed patient population at a starting rate within 5 to 20 ng/kg/min.
A generic or 505(b)(2) applicant could face infringement exposure if its proposed labeling includes:
- A starting dose of 5 ng/kg/min.
- A starting dose of 10 ng/kg/min.
- A starting dose of 20 ng/kg/min.
- A starting-dose range of 5 to 20 ng/kg/min.
- Instructions to increase the dose to 30 or 40 ng/kg/min.
- Treatment instructions covering a period within 15 minutes to five days.
The claim language creates a label-based infringement issue. Even where a product is chemically identical to angiotensin II, liability would depend on the approved labeling, marketing conduct, and whether the claimed clinical use is encouraged or intentionally promoted.
A narrow label that excludes the claimed patient conditions or removes the claimed dosing instructions could reduce risk, but it may also undermine commercial utility because the claimed regimen is closely aligned with the clinical use of intravenous angiotensin II in distributive or vasodilatory shock settings.
How do the claims apply to Giapreza and human angiotensin II?
The claims expressly cover human angiotensin II through claims 17 and 18. The product most closely associated with this patent landscape is Giapreza, whose active ingredient is synthetic human angiotensin II, also known as angiotensin II acetate in the product context.
The patent does not appear, from the supplied claims, to require a particular salt, excipient, concentration, container, or manufacturing method. A competing product using the same active peptide could therefore remain within the method claims even if it used a different formulation or manufacturing process.
The product label is commercially important because dosing instructions can determine whether the marketed use overlaps the patented regimen. FDA labeling for Giapreza identifies intravenous use in adults with septic or other distributive shock and includes dose initiation and titration instructions that are relevant to the claim boundaries. (U.S. Food and Drug Administration, n.d.)
What formulations are protected by U.S. Patent 10,500,247?
The supplied claims do not claim a formulation.
They do not specify:
- Concentration of angiotensin II.
- Buffer system.
- pH.
- Stabilizer.
- Excipient.
- Vial or container.
- Reconstitution solvent.
- Shelf life.
- Freeze-drying or lyophilization.
- Infusion-solution compatibility.
A competitor could potentially use a different formulation and still practice the method claims if it administers angiotensin II at the claimed initial rate to a qualifying patient.
That distinction matters in freedom-to-operate analysis. A formulation patent may be avoided by changing excipients or manufacturing conditions. A dosing method patent is harder to avoid when the clinical protocol naturally uses the protected dose range.
Does the patent cover acute kidney injury treatment?
Yes. Acute kidney injury is one of the expressly identified patient conditions in claims 1 and 10.
The claims do not require that the patient have only acute kidney injury. The wording also reaches patients suffering from refractory hypotension or severe hypotension. The alternatives create separate paths to infringement.
The claim does not state that angiotensin II must improve renal function. It requires treatment of low blood pressure in a patient with the specified condition. A product label or clinical protocol could therefore raise infringement issues even if the therapeutic objective is hemodynamic stabilization rather than direct treatment of renal injury.
What role do the dose ranges and “about” language play?
The central numerical limitation is the initial rate of approximately 5 to 20 ng/kg/min.
The word “about” creates potential claim-construction disputes around the endpoints. It does not necessarily make every dose near 5 or 20 ng/kg/min infringing. Courts generally assess the intrinsic evidence, specification, prosecution history, and technical meaning of the term in context.
The most defensible literal overlap is likely at the expressly recited values:
- 5 ng/kg/min.
- 10 ng/kg/min.
- 20 ng/kg/min.
- Any starting range expressly stated as 5 to 20 ng/kg/min or 10 to 20 ng/kg/min.
A dose below 5 ng/kg/min or above 20 ng/kg/min may avoid literal infringement of claim 1, but other claims, the doctrine of equivalents, or a different patent could remain relevant.
What generic launch scenarios exist?
Launch using a full label
A full-label generic or 505(b)(2) product that reproduces the patented dosing protocol would face the highest risk. A Paragraph IV certification could trigger Hatch-Waxman litigation if the patent is listed in the Orange Book for the relevant reference product. (U.S. Food and Drug Administration, n.d.-b)
Carved-out labeling
A proposed label could omit a patented indication or dosing instruction under the section viii procedure. The effectiveness of that strategy would depend on the precise Orange Book listing, the reference label, the remaining approved uses, and whether the marketed product would still induce use of the patented method.
Delayed commercial entry
The applicant could accept a later launch date, settle litigation, or launch subject to a license or covenant not to sue. The commercial value of that pathway depends on the patent’s enforceable term and any additional patents covering the product.
Non-infringing dosing protocol
A competitor could seek a starting regimen outside the claimed range. This approach would be clinically constrained because dose selection is tied to the approved label, patient severity, blood-pressure response, and safety monitoring.
When does U.S. Patent 10,500,247 lose exclusivity?
The patent issued on December 10, 2019. Patent expiration cannot be calculated accurately from the claim text alone because the controlling term depends on the earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.
The claims supplied do not establish:
- The earliest effective filing date.
- Patent-term adjustment.
- Patent-term extension under 35 U.S.C. § 156.
- A terminal disclaimer.
- Any post-grant disclaimer or disclaimer of individual claims.
Accordingly, the grant date is established, but the enforceable expiration date is not established by the supplied material. A term analysis must use the USPTO patent record and any FDA patent-term-extension determination. (United States Patent and Trademark Office, n.d.)
What is the Orange Book status of U.S. Patent 10,500,247?
The supplied claim text does not establish whether U.S. Patent 10,500,247 is currently listed in the FDA Orange Book, which reference product it covers, or the use code assigned to it.
If listed, its commercial significance would depend on whether the listing identifies:
- The angiotensin II product.
- The treatment of hypotension in the relevant patient population.
- The claimed dosing regimen.
- A method-of-use code broad enough to cover a proposed generic label.
Orange Book listing is not equivalent to ultimate validity or enforceability. A listed patent can be challenged through Paragraph IV litigation, post-grant proceedings, declaratory judgment actions, or later invalidity defenses.
Which companies are relevant to the competitive landscape?
The commercial landscape centers on the holder or licensee of the angiotensin II product rights and potential entrants using:
- Generic human angiotensin II.
- A 505(b)(2) application.
- Hospital-compounded or alternative-source angiotensin II, where legally and commercially viable.
- Other vasopressors, including norepinephrine, vasopressin, epinephrine, and phenylephrine.
Angiotensin II does not face a conventional biosimilar pathway because it is a chemically synthesized peptide drug rather than a biologic licensed under the Public Health Service Act. The relevant entry route is generally an ANDA, 505(b)(2) application, or another applicable abbreviated pathway, not a biosimilar application.
How strong is the patent estate based on these claims?
The claims have meaningful commercial scope but a narrower technical foundation than a composition or formulation patent.
| Strength factor |
Assessment |
| Coverage of core dosing protocol |
Strong |
| Coverage of human angiotensin II |
Expressly included |
| Formulation coverage |
None apparent from supplied claims |
| Manufacturing coverage |
None apparent |
| Device coverage |
None apparent |
| Patient-population coverage |
Broad within AKI, refractory hypotension, and severe hypotension |
| Label-based infringement risk |
Potentially significant |
| Design-around flexibility |
Moderate, but clinically constrained |
| Biosimilar relevance |
Low; product is not a conventional biologic |
| Vulnerability to invalidity attacks |
Dependent on written description, enablement, obviousness, prosecution history, and prior-art dosing disclosures |
The most vulnerable aspects may be the numerical dosing ranges, overlap among dependent claims, and whether the specification supports the full breadth of the claimed patient populations, treatment durations, and titration endpoints. The strongest practical position is likely the combination of a defined patient population with an expressly recited initial dose.
What patent litigation or settlement agreements affect the patent?
No litigation history, Paragraph IV action, settlement agreement, or license can be established from the claim text provided. The claims alone do not show whether the patent has been asserted, challenged, narrowed, invalidated, disclaimed, or licensed.
That absence of information prevents a reliable determination of current litigation risk, enforceability, or market-entry restrictions.
Key Takeaways
- U.S. Patent 10,500,247 is a dosing and method-of-treatment patent for angiotensin II.
- Claim 1 covers an initial rate of approximately 5 to 20 ng/kg/min in human patients with low blood pressure and AKI, refractory hypotension, or severe hypotension.
- Claim 10 adds upward titration and treatment duration of approximately 0.25 to 120 hours.
- Claims 17 and 18 expressly cover human angiotensin II.
- The supplied claims do not cover formulation, manufacturing, container, or delivery-device technology.
- A full-label generic or 505(b)(2) product using the claimed starting dose would face the highest infringement exposure.
- Angiotensin II is not subject to a conventional biosimilar pathway.
- The grant date is December 10, 2019, but the expiration date cannot be determined from the claims alone.
- Current Orange Book listing, Paragraph IV challenges, litigation, licenses, settlements, and enforceability are not established by the supplied material.
Frequently Asked Questions
Does Patent 10,500,247 cover all angiotensin II use?
No. It covers specified treatment methods involving low blood pressure, defined patient conditions, and an initial dosing range of approximately 5 to 20 ng/kg/min.
Does changing the angiotensin II formulation avoid the patent?
Not necessarily. The supplied claims are formulation-neutral. A different formulation could still infringe if the claimed treatment method is practiced.
Is a 10 ng/kg/min starting dose specifically covered?
Yes. Claim 3 expressly recites an initial rate of approximately 10 ng/kg/min, and claim 12 recites the same starting rate with titration and duration limitations.
Can a competitor avoid the patent by using a starting dose below 5 ng/kg/min?
That may avoid literal infringement of the stated initial-rate range, but infringement depends on the complete protocol, claim construction, equivalents, other patents, and the marketed label.
Does the patent protect renal recovery outcomes?
No. The supplied claims require treatment of low blood pressure in a patient with acute kidney injury or another specified condition. They do not require improved renal function as a claim element.
References
U.S. Food and Drug Administration. (n.d.-a). Giapreza (angiotensin II) injection prescribing information.
U.S. Food and Drug Administration. (n.d.-b). Approved drug products with therapeutic equivalence evaluations: Orange Book.
United States Patent and Trademark Office. (n.d.). U.S. Patent No. 10,500,247, Patent Center and patent term information.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
U.S. Congress. (2010). Patient Protection and Affordable Care Act, Biologics Price Competition and Innovation Act, 42 U.S.C. § 262.
