Scope and Claims Analysis for US Patent 11,918,622 (Bivalirudin Ready-to-Use IV Liquid for HIT/PCI)
US 11,918,622 claims a tightly defined intravenous (IV) ready-to-use liquid bivalirudin formulation and a method of inhibiting blood clots using that formulation. Claim scope centers on (i) a specific composition recipe (bivalirudin concentration, PEG 400, sodium acetate level and identity, and water), (ii) pH tightly constrained to >5.0–5.7 (with dependent claims narrowing to ~5.25 and ranges 5.1–5.4), (iii) stability/impurity growth over 12 months at refrigerated temperatures (with a “no more than ~9%” total impurity increase measured by HPLC at 215 nm), (iv) storage at 2–8°C, and (v) specific formulation exclusions (no reconstitution from lyophilized product and no dilution from concentrate; in narrower claims, no sodium chloride and no dextrose). The patent is framed as a method claim, but the limitations are product-defining, making it enforceable primarily against manufacture and use of an infringing ready-to-use liquid.
What is the scope of US Patent 11,918,622 and what do its claims actually cover?
Short answer: The patent covers IV administration of a ready-to-use bivalirudin liquid with a specific excipient system (PEG 400 + sodium acetate) and tightly controlled pH and stability, including constraints on impurities over refrigerated storage and product format (not reconstituted or diluted from a concentrate).
Core claim architecture
Independent claims are drafted as “method of inhibiting blood clots” claims where the method steps are primarily supplying the infringing composition:
- Intravenously administer a therapeutically effective amount.
- Composition must be a “ready-to-use liquid” meeting multiple parameters.
- The composition must be prepared by mixing specified ingredients.
- The composition must be stored at 2–8°C prior to administration.
- The composition must have pH in the range >5.0 to 5.7.
- Several dependent claims narrow to excipient identity, pH sub-ranges, impurity growth during storage, salt form, osmolality, and clinical use setting (HIT/HITTS undergoing PCI).
Claim scope is “product-by-process + use” in practice
While the claims are “method” claims, the infringement hook is the composition composition and its defining parameters. The “prepared by mixing …” language operates as a product-by-process constraint. Practically, a manufacturer could still infringe if the final product matches claim requirements even if process steps are not identical, but in US litigation, process limitations can matter depending on how courts interpret product-by-process and whether the process step is treated as a distinct limitation vs. merely describing the manufacturing result.
What are the independent claim limitations (Claim 1, Claim 9, Claim 16) that control infringement risk?
Claim 1 (broadest in your excerpt)
Infringing composition must be:
- Ready-to-use liquid for IV administration.
- Contains:
- ~5 mg/mL bivalirudin or a salt thereof
- ~0.8 mg/mL sodium acetate
- ~100 mg/mL PEG 400
- water
- optional glacial acetic acid and/or sodium hydroxide
- Composition preparation:
- prepared by mixing bivalirudin (or salt), sodium acetate, PEG 400, and water
- optionally with glacial acetic acid and/or sodium hydroxide
- Storage:
- stored at 2–8°C prior to administration
- pH:
Key scope takeaways for freedom-to-operate (FTO):
- Concentrations are not recited as wide “about” ranges beyond “about” for drug and key excipients; enforcement typically still focuses on whether the accused product meets the numeric boundaries as construed.
- The salt of bivalirudin is flexible in Claim 1 (“or a salt thereof”), widening scope.
- pH and stability are the strongest differentiators vs. many generic or reformulation attempts.
Claim 9 (excludes certain excipients and narrows product recipe)
Claim 9 limits the sodium acetate identity and adds excipient exclusions:
- Sodium acetate is sodium acetate trihydrate.
- Composition does not comprise sodium chloride or dextrose.
- Still requires pH >5.0 to 5.7.
- Prepared by mixing bivalirudin (salt), sodium acetate, PEG 400, and water (no optional acids/bases stated in this claim as in Claim 1).
- Still requires ready-to-use liquid and implied IV administration method.
Practical effect: If an accused product uses NaCl or dextrose, it may avoid Claim 9 while potentially still falling within Claim 1 depending on whether NaCl/dextrose are present and whether Claim 1 has no exclusion (your Claim 1 excerpt does not exclude NaCl/dextrose).
Claim 16 (free of NaCl/dextrose + bivalirudin trifluoroacetate + impurity growth requirement)
Claim 16 is the narrowest “recipe lock” in your excerpt:
- Ready-to-use liquid.
- bivalirudin in the form of trifluoroacetate (explicit).
- ~5 mg/mL bivalirudin trifluoroacetate (free base basis).
- ~0.8 mg/mL sodium acetate trihydrate.
- ~100 mg/mL PEG 400.
- water.
- Composition is free of sodium chloride and dextrose.
- pH >5.0 to 5.7.
- Stability constraint: percentage of total impurities increases by no more than about 9% from manufacture up to 12 months storage at 5°C as determined by HPLC at 215 nm.
- Composition prepared by mixing bivalirudin trifluoroacetate, sodium acetate, PEG 400, and water.
- Also includes “not reconstituted” style product-format limitation via Claim 16 (“not reconstituted from a lyophilized composition or diluted from a liquid concentrate” is included in Claim 20 in your list, while Claim 16 text includes the “composition has not been reconstituted…” element in the method chain you provided as part of Claim 16’s limitations set).
Practical effect: Claim 16 is harder to design around because it binds salt identity (trifluoroacetate), excipient exclusions (NaCl/dextrose), and a quantified impurity growth metric.
Which formulation parameters are “must-have” versus “optional” in US 11,918,622?
Must-have parameters (high infringement relevance)
Across your excerpt, these repeatedly appear as required:
- Ready-to-use liquid dosage form (format requirement).
- IV administration for inhibiting blood clots.
- bivalirudin concentration: about 5 mg/mL (free base basis depending on claim).
- PEG 400: about 100 mg/mL.
- Sodium acetate: about 0.8 mg/mL (tri-hydrate in claims 2/9/16).
- Water as solvent.
- Storage at 2–8°C prior to administration.
- pH: >5.0 to 5.7.
- Impurity growth metric in claims that include it (Claim 4, Claim 11, Claim 16):
- no more than about 9% total impurity increase at 5°C over 12 months, measured by HPLC at 215 nm.
- Clinical usage setting in HIT/HITTS with PCI (claims 7, 14, 19).
Optional parameters (narrower control)
- In Claim 1, glacial acetic acid and/or sodium hydroxide are optional for adjusting pH or formulation behavior. In other claims, those optionality statements are absent.
Exclusion constraints (designed to carve out alternative vehicles)
- Claim 9: no sodium chloride; no dextrose.
- Claim 16: free of sodium chloride and dextrose.
- Claims 8/15/20 (product format): composition has not been reconstituted from a lyophilized composition or diluted from a liquid concentrate.
These exclusion and format limitations can be decisive against alternative commercial supply models (lyophilized, concentrate + dilution).
How do the dependent claims narrow pH, impurities, osmolality, and bivalirudin salt form?
pH narrowing
- Claim 3: pH 5.1 to 5.4.
- Claim 10: pH about 5.25.
- Claim 21: pH about 5.25.
- Claim 1 baseline: pH >5.0 to 5.7.
Why it matters: Many formulation alternatives can still be “buffers” but miss the specific pH corridor. If an accused product targets pH 6.0 or 4.8, it likely avoids these dependent pH claims, but may still fall under the independent “>5.0 to 5.7” claim if within that corridor.
Impurity stability metric
- Claim 4: total impurities increase by no more than about 9% after 12 months at 5°C; measured by HPLC at 215 nm.
- Claim 11 mirrors the same in the claim-10 context.
- Claim 16 includes the same impurity growth constraint.
Why it matters: This is a quantitative stability/performance limitation. It can force an accused formulation into objective testing territory, using manufacturing timepoints and a defined analytical method/wavelength.
Bivalirudin salt form
- Claim 5: bivalirudin is trifluoroacetate salt (adds salt specificity).
- Claim 13: same in claim-10 context.
- Claim 16: trifluoroacetate is explicit and tied to the full recipe and stability requirement.
Why it matters: If an accused product uses bivalirudin acetate, sulfate, or free base basis with a different salt counterion, it can avoid trifluoroacetate-dependent claims while still potentially implicating broader “salt thereof” language in Claim 1.
Osmolality
- Claim 6: osmolality about 200 to about 600 mOsm/kg.
Why it matters: This can be used to distinguish formulations with different tonicity modifiers or different effective molecular contributions. Osmolality is not always controlled by simple recipe substitution, especially when PEG 400 dominates and water content shifts.
Target patient population and procedure
- Claim 7: HIT and/or HITTS undergoing PCI.
- Claim 14 and Claim 19: same patient/procedure context tied to narrower composition claims.
Why it matters: Method-of-use claims can be asserted based on who receives the drug and for what clinical scenario. For branded manufacturer enforcement, these claims can also align with indications and how prescribers administer the IV bivalirudin.
What do claims say about “ready-to-use” format and reconstitution/concentration models?
Your excerpt includes a format-limitation cluster:
- Claim 8: composition has not been reconstituted from a lyophilized composition or diluted from a liquid concentrate.
- Claim 15: similar limitation tied to claim 10.
- Claim 20: similar limitation tied to claim 16.
Scope impact:
- This can exclude infringement by reformulation strategies that provide the drug as lyophilized powder or as a concentrate requiring dilution to reach the final parameters.
- If a product is a concentrate but is diluted to yield the claimed final composition, infringement may hinge on whether the accused process is considered “diluted from a liquid concentrate” even if the final diluted solution matches the claimed pH/impurity/osmolality. The claims, as written, appear to bar that supply model.
How strong is the patent estate for this chemistry and what are the most likely design-arounds?
Based on claim content alone, US 11,918,622 is strongest where the accused product matches:
- the exact formulation architecture (bivalirudin ~5 mg/mL, Na acetate ~0.8 mg/mL, PEG 400 ~100 mg/mL, water),
- pH corridor (>5.0 to 5.7 and potentially ~5.25),
- storage at 2–8°C prior to administration, and
- stability requirement (<= ~9% total impurity growth after 12 months at 5°C, HPLC 215 nm), and
- product supply format (ready-to-use vs reconstitution/dilution),
- and in narrow claim sets, bivalirudin trifluoroacetate and absence of NaCl/dextrose.
Most plausible design-arounds (derived from claim limitations)
- Change pH outside >5.0–5.7 or outside the ~5.25 target.
- Swap excipient system: alter sodium acetate form/amount or replace PEG 400 with a different polymer or different concentration.
- Change salt form: avoid trifluoroacetate where trifluoroacetate-dependent claims are asserted.
- Introduce NaCl or dextrose to step around NaCl/dextrose-free dependent claims (note: this may still fall under Claim 1 if Claim 1 does not exclude those excipients).
- Use a different supply format: lyophilized or concentrate models to avoid the “not reconstituted/diluted from concentrate” limitation.
- Stability/impurity divergence: adjust formulation and manufacturing controls to produce a total impurity increase that exceeds the “no more than ~9%” criterion (this avoids specific stability-dependent claims).
Enforcement risk shifts depending on which claim is asserted. If asserted on Claim 1, NaCl/dextrose additions might not be enough if other limitations still match. If asserted on Claim 9 or Claim 16, the NaCl/dextrose-free and trifluoroacetate + impurity constraints become decisive.
What is the likely patent claim coverage relative to alternative bivalirudin liquid IV products?
Comparison matrix: claim-driven “match” logic
| Feature |
Matches Claim 1 |
Matches Claim 9 |
Matches Claim 16 |
| Ready-to-use IV liquid |
Required |
Required |
Required |
| Bivalirudin ~5 mg/mL (salt acceptable in Claim 1) |
Yes |
Yes |
Must be trifluoroacetate |
| Sodium acetate ~0.8 mg/mL |
Yes |
Na acetate trihydrate required |
Na acetate trihydrate required |
| PEG 400 ~100 mg/mL |
Yes |
Yes |
Yes |
| Water solvent |
Yes |
Yes |
Yes |
| pH >5.0 to 5.7 |
Yes |
Yes |
Yes |
| Storage 2–8°C prior to admin |
Yes |
Yes (via claim chain) |
Yes |
| HPLC total impurity increase ≤ ~9% after 12 months at 5°C |
Not in your excerpt of Claim 1 |
Not in your excerpt of Claim 9 |
Required |
| No sodium chloride |
Not excluded in Claim 1 (based on your excerpt) |
Excluded |
Excluded |
| No dextrose |
Not excluded in Claim 1 (based on your excerpt) |
Excluded |
Excluded |
| Not reconstituted/diluted from concentrate |
Included in dependent claims (noted in claims 8/15/20) |
Included in dependent chain (claims 15/20) |
Included in dependent chain (claims 20) |
This matrix shows why the patent can still reach a range of formulations under Claim 1, but how narrower claims (9/16) meaningfully limit the viable market segment for safe design-around.
Where would patent litigation and FDA/Orange Book strategy typically focus for US 11,918,622-type claims?
Litigation focus points (claim construction hotspots)
- “ready-to-use” and “not reconstituted/diluted from concentrate”
- pH measurement at specification conditions
- “about” numerical tolerances for concentrations and osmolality
- the HPLC 215 nm impurity growth methodology and how “total impurities” is defined and calculated
- whether a different manufacturing path still satisfies the “prepared by mixing …” limitations (product-by-process)
Regulatory and commercial focus points
- If the drug is marketed as an IV bivalirudin liquid, challengers and generic developers would evaluate whether their formulation is positioned as:
- a ready-to-use product vs a concentrate or lyophilized product
- a Na acetate/PEG-based system with pH in the 5.1–5.4 or ~5.25 corridor
- trifluoroacetate vs other salts
- impurity performance aligned to the “<= ~9%” criterion
Key Takeaways
- US 11,918,622 is a method-of-use patent that is effectively enforced through a product-definition strategy: an IV ready-to-use bivalirudin liquid with PEG 400 and sodium acetate, refrigerated storage, and a strict pH corridor (>5.0 to 5.7).
- The most enforceable differentiators are: pH (often narrowed to ~5.25), impurity stability after 12 months at 5°C measured by HPLC at 215 nm (<= ~9% total impurity increase), ready-to-use format (not reconstituted/diluted from lyophilized/concentrate models), and in narrower claims, absence of sodium chloride/dextrose and use of bivalirudin trifluoroacetate.
- Design-around risk is highest if an accused product matches the PEG 400 + sodium acetate + pH + storage profile. Risk drops if it changes supply format (lyo/concentrate), removes the NaCl/dextrose-free architecture, alters salt form away from trifluoroacetate, or fails the specific stability metric.
FAQs
1) What pH range does US 11,918,622 require for infringement?
Claim 1 requires pH greater than 5.0 to 5.7. Dependent claims narrow to 5.1–5.4 and “about 5.25.”
2) Does the patent require bivalirudin to be trifluoroacetate?
Not in Claim 1 (it covers bivalirudin or a salt thereof). It is required in the trifluoroacetate-dependent claims including Claim 5/13 and is explicit in Claim 16.
3) What stability test is claimed in US 11,918,622?
Total impurities must increase by no more than about 9% after 12 months storage at 5°C, measured by HPLC at 215 nm (appearing in the dependent claims and included in Claim 16).
4) Can a reconstituted lyophilized product infringe?
Claims in your excerpt require that the composition “has not been reconstituted from a lyophilized composition or diluted from a liquid concentrate,” which is designed to exclude those supply formats.
5) Which excipients are excluded in narrower claims?
Claim 9 and Claim 16 exclude sodium chloride and dextrose.
References
[No external sources were cited because the user provided only the claim text and did not provide prosecution history, publication dates, assignee, related patents, Orange Book listings, or litigation records.]
