US Patent 5,965,581: Scope, Claim Boundaries, and US Patent Landscape for a pH-Buffered IV Platelet Aggregation Inhibitor
US Patent 5,965,581 covers a specific intravenous (IV) formulation of a substituted propionic acid derivative (2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propionic acid) plus defined concentrations of common ionic excipients (NaCl, sodium citrate dihydrate, citric acid anhydrous), constrained by osmolality and pH windows. The patent also claims two IV methods for inhibiting blood platelet aggregation by administering a pharmaceutically effective amount of the claimed compositions.
What are the core claim pillars?
The patent is built on three layers of constraints:
-
Active ingredient identity and form
- The active is a single, highly specified chemical entity:
2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propionic acid.
- Dependent composition claims recite hydrochloride monohydrate as the administered/contained form (claims 3, 4, 7, 8), tying scope to specific salt form and hydration state.
-
Exact excipient concentration sets
- Each composition claim pins down a narrow excipient recipe in mg/mL terms:
- Sodium chloride
- Sodium citrate dihydrate
- Citric acid anhydrous
-
Physicochemical target ranges
- Each composition constrains:
- Osmolality window (two distinct bands appear)
- pH window (common to all, 5.5 to 6.5)
How do claim 1 and claim 2 define the composition scope?
Claim 1 scope (higher active concentration; lower citrate)
Composition (mg/mL):
- Active: 0.25 mg/mL 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propionic acid
- NaCl: 8 mg/mL
- Sodium citrate dihydrate: 2.7 mg/mL
- Citric acid anhydrous: 0.16 mg/mL
Constrained properties:
- Osmolality: 250 to 310 mOsmol/kg
- pH: 5.5 to 6.5
Claim 2 scope (lower active concentration; higher NaCl; lower citrate)
Composition (mg/mL):
- Active: 0.05 mg/mL
- NaCl: 9 mg/mL
- Sodium citrate dihydrate: 0.54 mg/mL
- Citric acid anhydrous: 0.032 mg/mL
Constrained properties:
- Osmolality: 255 to 345 mOsmol/kg
- pH: 5.5 to 6.5
Business implication for design-arounds
- The claims are not “any buffered isotonic IV.” They lock in two specific quantitative recipes (claim 1 and claim 2) with specific osmolality windows. A reformulation that keeps pH but materially changes citrate/NaCl ratios risks falling outside the literal concentration recitations and osmolality bands.
What do claims 3, 4, 7, and 8 add?
Claims 3 and 4 use the hydrochloride monohydrate form and recite essentially the same excipient classes but at different active concentrations and excipient concentrations, again with osmolality and pH limits.
Claim 3 scope (salt form; “claim 1-style” recipe)
Composition formed by combining (mg/mL):
- Active: 0.28 mg/mL 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propionic hydrochloride monohydrate
- NaCl: 8 mg/mL
- Sodium citrate dihydrate: 2.7 mg/mL
- Citric acid anhydrous: 0.16 mg/mL
Constrained properties:
- Osmolality: 250 to 310 mOsmol/kg
- pH: 5.5 to 6.5
Claim 4 scope (salt form; “claim 2-style” recipe)
- Active: 0.056 mg/mL hydrochloride monohydrate
- NaCl: 9 mg/mL
- Sodium citrate dihydrate: 0.54 mg/mL
- Citric acid anhydrous: 0.032 mg/mL
- Osmolality: 255 to 345 mOsmol/kg
- pH: 5.5 to 6.5
Claims 7 and 8: same targets with pH-adjusting-agent language
Claims 7 and 8 are closely aligned with claims 3 and 4 but add a functional statement:
- pH is within 5.5 to 6.5, with the note that pH may be adjusted if necessary using one or more pH adjusting agents.
Claim 7:
- Active: 0.28 mg/mL hydrochloride monohydrate
- NaCl: 8 mg/mL
- Sodium citrate dihydrate: 2.7 mg/mL
- Citric acid anhydrous: 0.16 mg/mL
- Osmolality: 250 to 310 mOsmol/kg
- pH: 5.5 to 6.5 (adjusted if necessary)
Claim 8:
- Active: 0.056 mg/mL hydrochloride monohydrate
- NaCl: 9 mg/mL
- Sodium citrate dihydrate: 0.54 mg/mL
- Citric acid anhydrous: 0.032 mg/mL
- Osmolality: 255 to 345 mOsmol/kg
- pH: 5.5 to 6.5 (adjusted if necessary)
Business implication
- The pH-adjusting-agent phrasing widens practical manufacturing flexibility but does not broaden the core excipient concentrations. It mostly addresses the reality that pH may drift during compounding while still claiming the recipe and target pH.
What is the method-of-use claim scope?
Claim 5 and claim 6
Both claims recite:
- A method for inhibiting aggregation of blood platelets in a patient
- IV administration of a pharmaceutically effective amount of the composition of claim 1 (claim 5) or claim 2 (claim 6)
Scope notes
- These are use claims tied to the formulations of claims 1 and 2, not to the salt-formulation claims (3, 4, 7, 8) in your provided text.
- Even if a salt-formulation could function similarly, literal coverage depends on whether that formulation is the one “of claim 1” or “of claim 2.”
Claim map: numerical boundaries and what changes break coverage
| Claim |
Active form in claim |
Active (mg/mL) |
NaCl (mg/mL) |
Na-citrate (mg/mL) |
Citric acid (mg/mL) |
Osmolality (mOsm/kg) |
pH range |
| 1 |
Acid |
0.25 |
8 |
2.7 |
0.16 |
250-310 |
5.5-6.5 |
| 2 |
Acid |
0.05 |
9 |
0.54 |
0.032 |
255-345 |
5.5-6.5 |
| 3 |
HCl monohydrate |
0.28 |
8 |
2.7 |
0.16 |
250-310 |
5.5-6.5 |
| 4 |
HCl monohydrate |
0.056 |
9 |
0.54 |
0.032 |
255-345 |
5.5-6.5 |
| 7 |
HCl monohydrate + pH adjust language |
0.28 |
8 |
2.7 |
0.16 |
250-310 |
5.5-6.5 |
| 8 |
HCl monohydrate + pH adjust language |
0.056 |
9 |
0.54 |
0.032 |
255-345 |
5.5-6.5 |
What most likely drives non-infringement (literal)
- Changing the active concentration away from the claim’s numeric recitations.
- Shifting NaCl or citrate/citric acid ratios such that you no longer match the mg/mL recitations.
- Achieving a pH outside 5.5-6.5 or osmolality outside the specified bands.
Where is the “patent moat” in this document?
The patent moat is not the active compound identity alone. It is the combination of:
- A fixed quantitative formulation recipe (specific mg/mL excipients),
- A tight pH window,
- A defined osmolality band, and
- A salt/hydrate-specific version for certain composition claims,
- Plus IV method-of-use claims for the claim 1 and claim 2 recipes.
That construction means competitive risk is concentrated around:
- Direct line extensions of the same IV product format,
- Alternate salt form strategies that still land within the same recipe and property windows,
- And patient-facing product profiles where osmolality and pH are engineered to meet the same targets.
How this claim structure affects the US patent landscape (practical view)
Within a US landscape, this type of filing typically clusters around:
- Formulation patents (buffers, tonicity, stability),
- Salt form patents (hydrates/hydrochloride),
- And method-of-use claims (platelet aggregation inhibition).
For business planning, the key question is less “does the active drug exist” and more “what formulation and salt are being sold and under what pH/osmolality specification.”
Coverage sensitivity by design choice
-
Salt/hydrate selection
- If competitors use a different salt form (or a different hydrate state), they can potentially avoid claims 3, 4, 7, 8 while still using a buffer system. But they still risk claims 1 and 2 if they use the free acid and match the recipe windows.
-
Buffer system
- The claims specifically require sodium citrate dihydrate and citric acid anhydrous at the recited mg/mL levels. Substituting other buffers (even if pH-equivalent) can break literal scope.
-
Tonicity strategy
- Osmolality bounds are part of the claim. A company that changes tonicity agent(s) to hit a different osmolality band can aim to fall outside the stated osmolality range.
-
Dosage form linkage
- The method claims in your provided text are tied to claim 1 and claim 2 compositions and specifically state intravenous treating.
Risk framing for investors and R&D teams
If you are developing an IV platelet aggregation inhibitor
- Treat this as a formulation-with-property constraint patent.
- A product that meets therapeutic function but uses a materially different mg/mL excipient recipe and hits different osmolality/pH likely avoids literal coverage of the listed claims.
If you are evaluating freedom-to-operate (FTO) for formulation changes
Focus diligence on:
- Exact mg/mL excipient levels (NaCl, sodium citrate dihydrate, citric acid anhydrous),
- Documented osmolality test results and pH measurement methods,
- The active form in the final drug product (acid vs hydrochloride monohydrate),
- Whether the clinical protocol is written as “IV platelet aggregation inhibition” and references a pharmaceutically effective dose derived from the claim 1 or claim 2 recipe.
What is missing for a full patent landscape mapping?
A complete US landscape for US 5,965,581 requires bibliographic data and citation trees (file history, family members, examiner citations, and later re-issues/reexams), which are not provided in your input. Without those, a full enumeration of related US application publications, continuation patents, and patent families cannot be produced accurately.
Accordingly, the analysis above is limited to the claim scope you provided and the practical coverage boundaries implied by the claim language.
Key Takeaways
- US 5,965,581 covers IV compositions of a specific substituted propionic acid derivative with hard numeric excipient concentrations and hard property limits (osmolality and pH).
- Claims split into two main formulation recipes (claim 1 and claim 2) and two salt-form variations (claims 3, 4, 7, 8), with osmolality bands: 250-310 and 255-345 mOsmol/kg, and a shared pH 5.5-6.5 window.
- The method claims cover IV platelet aggregation inhibition by administering a pharmaceutically effective amount of the claim 1 or claim 2 composition.
- Literal non-infringement is most plausibly achieved by moving off the recited mg/mL excipient recipe and/or the osmolality/pH windows, and (for certain claims) by using a different active salt/hydrate form.
FAQs
1) Does the patent claim any IV platelet aggregation inhibitor generally?
No. The method claims are tied to administering the specific compositions recited in claims 1 and 2 for inhibiting platelet aggregation.
2) Are osmolality and pH required in every composition claim?
Yes. Each composition claim requires the composition to have osmolality within the stated range and pH within 5.5 to 6.5.
3) What excipients are locked by concentration?
NaCl, sodium citrate dihydrate, and citric acid anhydrous are each recited at specific mg/mL levels for each composition claim set.
4) Does the salt form matter?
Yes. Claims 3, 4, 7, and 8 specify the active as hydrochloride monohydrate, while claims 1 and 2 recite the free acid form.
5) Can pH be adjusted using other agents?
Claims 7 and 8 explicitly allow pH adjustment “if necessary” using one or more pH adjusting agents, but pH still must remain within 5.5 to 6.5 and the other concentration and osmolality requirements remain in place.
References
[1] US Patent No. 5,965,581 (claim text as provided by user).
