United States Patent 10,335,451: Claims, Scope, and U.S. Patent Landscape for Angiotensin II Titration in Septic Shock Hypotension
What does US Drug Patent 10,335,451 claim, at the method level?
US 10,335,451 is directed to a method of treating hypotension in a human subject with septic shock using Angiotensin II with a defined initial infusion rate, titration scheme, and target hemodynamic outcome.
Claim architecture (high-level)
- Core clinical objective: treat hypotension in septic shock.
- Drug: Angiotensin II.
- Therapeutic protocol:
- Start at about 20 ng/kg/min.
- Titrate upward to about 30 and/or about 40 ng/kg/min.
- Infuse over a time window (from 0.25 hours up to 120 hours, with dependent narrowing to 1 to 7 hours).
- Titrate to achieve and maintain mean arterial pressure (MAP) of about 65 mmHg (with dependent narrowing on duration).
- Background therapy: method can be practiced during one or more vasopressors, including specified agents (norepinephrine, vasopressin, epinephrine, dopamine).
- Incorporated protocol variants: claims repeat the same Angiotensin II protocol both with and without the vasopressor limitation, via dependent claim sets.
What is the practical claim scope (who is covered and what must be done)?
The claims are drafted as administering methods with quantified infusion parameters. Coverage hinges on matching the protocol steps, not on patient selection biomarkers beyond “septic shock” and “hypotension.”
Step-by-step elements that drive infringement risk
A practicing method falls within the independent method definitions if it meets the following:
- Population: “a human subject having septic shock” (and hypotension).
- Intervention: administering Angiotensin II.
- Dose initiation: initial rate about 20 ng/kg/min (independent claim 1) or rate range 20 to 40 ng/kg/min (independent claim 24).
- Titration:
- Upshift options to about 30 and/or about 40 ng/kg/min (claims 2-4, 15-17).
- “One or more times by about 10 ng/kg/min” (claims 4 and 17).
- Administration duration:
- 0.25 hours to 120 hours (claims 5, 18).
- Or narrower: 1 hour to 7 hours (claims 6, 19).
- Hemodynamic target:
- Titrate to achieve MAP about 65 mmHg (claims 7-8, 20-21).
- Maintain MAP about 65 mmHg for 0.25 to 120 hours or 1 to 7 hours (claims 9-10, 22-23).
- Concomitant vasopressors (only for the dependent chain starting at claim 11 and later):
- One or more vasopressors (claim 11).
- Listed vasopressors (claim 12).
- Individual listing embodiments include norepinephrine (claim 13) and vasopressin (claim 14).
What “about” does to boundary lines
The term “about” wraps most numeric limits:
- Initial: “about 20 ng/kg/min”
- Titration: “about 30” and “about 40”
- Rate steps: “about 10 ng/kg/min”
- Timing: “about 0.25 hours” to “about 120 hours” and “about 1 hour” to “about 7 hours”
- MAP target: “about 65 mmHg” and maintenance of “about 65 mmHg”
From an enforcement standpoint, “about” typically creates a flexible capture zone around the stated numbers rather than a hard exclusion at exact boundaries.
Which dosing and monitoring features create the strongest independent coverage?
Two independent anchors exist: claim 1 and claim 24.
Independent claim 1 (initial rate anchor + titration + duration and/or MAP dependent elements)
Claim 1: treat septic shock hypotension by administering Angiotensin II at an initial rate about 20 ng/kg/min.
Dependent claim coverage narrows protocol details:
- Titrate up to about 30 and/or about 40 ng/kg/min (claims 2-3)
- Titrate “one or more times by about 10 ng/kg/min” (claim 4)
- Administer over 0.25 to 120 hours (claim 5) or 1 to 7 hours (claim 6)
- Titrate to reach MAP about 65 mmHg (claim 7-8)
- Maintain MAP about 65 mmHg for 0.25 to 120 hours (claim 9) or 1 to 7 hours (claim 10)
Practical effect: claim 1 covers the method class where the infusion protocol begins at the “about 20” starting rate. If the protocol then proceeds through any of the dependent-defined features, those dependent claims add narrower capture.
Independent claim 24 (range anchor)
Claim 24: treat septic shock hypotension by administering Angiotensin II at from about 20 ng/kg/min to about 40 ng/kg/min.
Dependent claim coverage:
- Specific fixed embodiments at about 30 and about 40 (claims 25-26)
Practical effect: claim 24 is broader on start conditions because it uses a dose-rate range rather than an initial-rate requirement. If a regimen fits within “about 20 to about 40,” claim 24 is a primary infringement target even if the patient was started elsewhere, depending on how “administering at a rate” is interpreted for multi-step regimens.
How does the vasopressor limitation change scope?
The claim set starting at claim 11 adds a concomitant therapy limitation: “undergoing treatment with one or more vasopressors.”
Claim 11-14 embodiments (vasopressor specificity)
- Claim 11: subject undergoing treatment with one or more vasopressors
- Claim 12: vasopressors selected from:
- norepinephrine
- vasopressin
- epinephrine
- dopamine
- Claim 13: norepinephrine embodiment
- Claim 14: vasopressin embodiment
Then the same Angiotensin II protocol is layered again:
- Titrate up to about 30 and about 40 (claims 15-16)
- Titrate in “about 10 ng/kg/min” steps (claim 17)
- Infusion time windows (claims 18-19)
- MAP titration and maintenance at about 65 mmHg (claims 20-23)
Practical effect: if an operator treats septic shock hypotension using Angiotensin II titration while the patient is on a vasopressor, the method more readily lands within the dependent chain. If no vasopressors are used, only the claim 1/24 line without claim 11’s limitation remains relevant.
What is the operational “protocol fingerprint” of this patent?
Across the claims, the method fingerprint is:
Dose and titration
- Start at about 20 ng/kg/min
- Titrate upward to about 30 and/or about 40 ng/kg/min
- Or titrate in increments of about 10 ng/kg/min
- Independent range: about 20 to about 40 ng/kg/min
Infusion duration
- 0.25 hours to 120 hours
- Narrow dependent: 1 to 7 hours
Hemodynamic targets
- Titrate to achieve MAP about 65 mmHg
- Maintain MAP about 65 mmHg for 0.25 to 120 hours
- Narrow dependent: maintain for 1 to 7 hours
Concomitant agents (dependent chain)
- Any vasopressor among: norepinephrine, vasopressin, epinephrine, dopamine
How does this translate into a design-around problem for generic or alternative Angiotensin II regimens?
Because the claims are protocol-driven with overlapping dose, time, and MAP endpoints, design-around must address at least one of the claim-critical elements:
- Dose-rate out of the range: avoid “about 20 to about 40 ng/kg/min” and avoid “initial about 20 ng/kg/min” (for claim 1).
- Avoid the specific step pattern: avoid a titration scheme “by about 10 ng/kg/min” and avoid moving to “about 30” or “about 40.”
- Avoid MAP target: use a different MAP setpoint than “about 65 mmHg,” including a different maintained MAP duration window.
- Avoid the vasopressor-dependent chain: if relevant, absence of concomitant vasopressors avoids claim 11 and dependent claims, but does not avoid claim 1/24 if Angiotensin II dosing/titration matches.
What does the U.S. patent landscape imply for freedom-to-operate (FTO)?
You asked for a “patent landscape,” but the only concrete inputs provided here are the claims text. No bibliographic data (assignee, filing date, publication number), no citation set, and no connected family members or continuations were provided. Without those, a complete, accurate U.S. landscape cannot be constructed from record-level sources without risking fabrication.
Under strict record-based analysis, the actionable landscape inference available from the claim text alone is limited to what would be expected mechanistically: the most likely closest prior art and competing claims around this domain cluster on:
- Angiotensin II use in septic shock hypotension,
- infusion initiation and titration rate ranges,
- MAP targets and maintenance durations,
- use with standard vasopressors.
But producing a definitive “landscape” (which patents, which claim overlaps, which family members, which likely expiration/term status, which continuations) requires bibliographic and document-level inputs not present in the prompt.
So what coverage does this patent likely control in practice?
Even without a broader family map, the claim set indicates the patent is designed to control a specific bedside protocol for Angiotensin II in septic shock:
The most enforceable set of claim requirements (highest-probability match)
The most likely infringement fact pattern is a hospital protocol that:
- starts Angiotensin II near 20 ng/kg/min,
- titrates upward toward 30 and/or 40 ng/kg/min,
- targets MAP 65 mmHg,
- runs infusion for hours in the range 0.25 to 120 (or 1 to 7 in narrower settings),
- often while patients receive norepinephrine or vasopressin.
Independent claim “dual entry points”
- If the regimen is anchored on starting near 20, claim 1 is the direct hook.
- If the regimen operates anywhere within 20 to 40, claim 24 captures that broader rate-range operation.
Key Takeaways
- US 10,335,451 claims a protocol for Angiotensin II in septic shock hypotension with initial about 20 ng/kg/min (claim 1) and/or about 20 to about 40 ng/kg/min (claim 24).
- The patent narrows further through titration to about 30 and/or about 40, step increases of about 10 ng/kg/min, infusion durations from 0.25 to 120 hours (or 1 to 7 hours), and MAP targeting/maintenance at about 65 mmHg.
- A dependent chain adds concomitant therapy coverage when the subject is on vasopressors, including norepinephrine and vasopressin.
- Practical design-around must shift at least one of the claim-critical variables: starting dose, rate range, titration step pattern, MAP target, or MAP maintenance window; and for the vasopressor-dependent claims, ensure the relevant concomitant therapy condition is not met.
FAQs
1) Does the patent require Angiotensin II to reach exactly 65 mmHg?
No. Claims use “about 65 mmHg” for both achieving and maintaining MAP.
2) Are fixed-dose regimens covered?
Yes. Claim 24 supports regimens within about 20 to about 40 ng/kg/min, and dependent claims specify administration at about 30 (claim 25) and about 40 (claim 26).
3) Is titration mandatory in all independent claims?
Claim 1 is anchored on an initial rate about 20 ng/kg/min and titration appears in dependent claims. Claim 24 is anchored on the administered rate range, which can be practiced with or without a specific titration path depending on how “administering at a rate” is executed.
4) Do the claims apply only when patients are on norepinephrine or vasopressin?
No. The vasopressor-dependent claims include norepinephrine, vasopressin, epinephrine, and dopamine. The protocol also has versions without that vasopressor limitation (via the claim 1 and claim 24 chain).
5) Can a shorter administration duration avoid the time-window limits?
The dependent claims narrow administration windows to about 1 to about 7 hours. If the method avoids those narrower dependent limitations, it may still fall within the broader about 0.25 to about 120 hours depending on actual duration.
References
[No sources were provided or retrievable from the prompt beyond the user-supplied claims text.]
