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Patent landscape, scope, and claims: |
US 11,723,887: Stable Ambient-Storage Treprostinil Salt Batches and Downstream Product Claims
US Patent 11,723,887 claims pharmaceutical batches and products built around a process that produces a salt of treprostinil (with diethanolamine as a key embodiment) that can be stored at ambient temperature while retaining lower levels of impurities relative to a treprostinil starting material that already contains impurities from prior alkylation and hydrolysis steps. The patent then ties that batch to a finished pharmaceutical product and to a two-stage method where the salt is stored at ambient temperature and only later converted to a drug product.
What does the patent claim in plain terms?
The claims revolve around three linked ideas:
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A composition-batch stability requirement
The batch must be (i) a treprostinil salt, (ii) stable at ambient temperature, (iii) prepared from a treprostinil starting batch with impurities, and (iv) have one or more impurities lower in the pharmaceutical batch than in the starting batch.
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A specific process knob to reduce impurities
Forming a salt by contacting treprostinil solution with a base reduces impurity levels that originate from prior alkylation and hydrolysis steps.
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A downstream product linkage
The ambient-storable batch is incorporated into a final product (carrier + therapeutically effective amount of the salt), and can be used in a method where storage occurs before later product preparation.
These ideas appear across independent claim 1 and independent-style claim 8, with multiple dependent claims specifying salt identity (diethanolamine), drying, manufacturing constraints (no column chromatography; no isolation), and a downstream storage-to-product conversion method.
Scope of Claim 1: stable ambient treprostinil salt batch with impurity reduction
Claim 1 is the core anchor. It covers:
- Product form: “A stable pharmaceutical batch of a salt of treprostinil”
- Stability: “can be stored at ambient temperature”
- Preparation method:
- providing “a starting batch of treprostinil having one or more impurities resulting from prior alkylation and hydrolysis steps”
- forming “a solution comprising treprostinil from said starting batch”
- contacting the solution with “a base to form a salt of treprostinil”
- Impurity reduction: “a level of one or more impurities found in the starting batch … is lower in the pharmaceutical batch”
- Quantity floor: “said pharmaceutical batch being at least 2.9 grams”
Practical read-across (claim scope boundaries)
Claim 1 is not limited to a particular treprostinil salt unless the dependent claims narrow it. As written, “a base” is broad and reads on any base that forms a treprostinil salt meeting the impurity reduction and ambient stability requirements. The key limitations for infringement or claim navigation are:
- the starting material is treprostinil with impurities attributed to alkylation + hydrolysis
- the process proceeds through solution formation then salt formation
- the salt batch shows lower impurity levels compared to the starting batch
- the batch size is >= 2.9 g
- stability at ambient temperature is required
Claim 1 elements in a compliance checklist
| Element |
Requirement in Claim 1 |
Scope impact |
| Batch identity |
“salt of treprostinil” |
Composition limited to salts, not free base |
| Stability |
“can be stored at ambient temperature” |
Enforces stability outcome |
| Starting impurities |
starting treprostinil has impurities “resulting from prior alkylation and hydrolysis steps” |
Ties to impurity origin from upstream chemistry |
| Conversion step |
“solution comprising treprostinil” contacted with “a base” |
Salt formation from solution is mandatory |
| Impurity outcome |
impurity level in starting batch is “lower in the pharmaceutical batch” |
Outcome-driven but measured against the input impurity level |
| Minimum batch size |
“at least 2.9 grams” |
Quantitative threshold for coverage |
How do dependent claims narrow Claim 1?
What do claims 2 and 3 specify about the salt batch?
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Claim 2: “The pharmaceutical batch of claim 1, wherein the pharmaceutical batch has been dried under vacuum.”
This narrows the covered embodiments to those where vacuum drying is used. It does not remove ambient storage stability, impurity reduction, or the salt-batch identity.
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Claim 3: “The pharmaceutical batch of claim 1, wherein the base is diethanolamine.”
This makes the diethanolamine salt explicit as a covered species.
What does claim 9 add about chromatography?
- Claim 9: “A pharmaceutical batch as claimed in claim 1, wherein no purification by column chromatography is performed between steps (a) and (b).”
This is anchored to claim 8’s process steps (a) and (b), not claim 1 alone. It constrains the manufacturing route: for relevant upstream pathways, no column chromatography occurs between alkylation (a) and hydrolysis (b).
Scope of Claim 4 and 5: formulation claims depend on the specific ambient-stable batch
Claim 4:
- “A pharmaceutical product comprising a carrier and a therapeutically effective amount of a salt of treprostinil,”
- where the salt is “from a pharmaceutical batch as claimed in claim 1.”
Claim 5:
- “wherein the salt is the diethanolamine salt of treprostinil.”
Scope implications
- Claim 4 is a formulation claim that is derivative of claim 1. The salt used must come from the claim 1 batch meeting impurity reduction and ambient stability.
- Claim 5 fixes the salt identity as the diethanolamine salt.
This means a product-level competitor cannot avoid claim 4 by changing the carrier, as long as the salt originates from the covered batch concept.
Scope of Claim 6 and 7: a storage-then-convert method
Claim 6:
- “A method of preparing a pharmaceutical product from a pharmaceutical batch as claimed in claim 1,”
- “comprising storing a pharmaceutical batch of a salt of treprostinil as claimed in claim 1 at ambient temperature and preparing a pharmaceutical product from the pharmaceutical batch after said storing.”
Claim 7:
- salt is the diethanolamine salt.
Scope implications
- Claim 6 is a process method that adds an explicit step: ambient-temperature storage before final product preparation.
- It focuses on timing and method sequence, not only on producing the batch.
Scope of Claim 8: manufacturing route with impurity reduction by forming the salt, plus downstream acidification
Claim 8 is the other major pillar. It recites a multi-step preparation and includes explicit route details:
- (a) Alkylating a benzindene triol
- (b) Hydrolyzing the product of step (a) to form a solution comprising treprostinil
- (c) Contacting the solution with a base to form a salt of treprostinil
- (d) Storing the salt at ambient temperature
- Thereafter acidifying the salt to form treprostinil
Impurity reduction limitation:
- “wherein forming the salt of step (c) reduces the amount of one or more impurities resulting from steps (a) and/or (b) in the pharmaceutical batch.”
Key scope points
- Claim 8 is not just “salt batch stability.” It ties the ambient-stable salt step to impurity suppression relative to impurities generated during steps (a) and/or (b).
- It includes a downstream acidification back to treprostinil after ambient storage of the salt.
How do claims 10 and 11 constrain claim 8’s internal handling?
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Claim 10: “wherein treprostinil in (b) is not isolated prior to (c).”
This blocks a route where treprostinil is isolated as a solid prior to salt formation. The treprostinil remains in the solution made by hydrolysis.
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Claim 11: “A pharmaceutical batch of treprostinil prepared by the method of claim 8.”
This creates a product-by-process claim for treprostinil (not only the salt), produced after the claim 8 salt storage and acidification sequence.
What is the patent landscape risk around these claim features?
The landscape question is less about “are salts of treprostinil known” and more about whether the market’s relevant competitors can land outside the specific combinations that 11,723,887 requires:
- Ambient storage stability of the salt
- Impurity reduction tied to salt formation
- Starting treprostinil with impurities from alkylation and hydrolysis
- No column chromatography between alkylation and hydrolysis (for the dependent variant)
- No treprostinil isolation before salt formation
- Diethanolamine salt appears as a clear favored embodiment
- Batch size at least 2.9 grams (for claim 1)
Without the full patent record (e.g., priority dates, prosecution history, claim charting against known treprostinil salt processes, assay definitions for “impurities,” and stability test parameters), an exact landscape map (which patents anticipate or are likely cited, which patents share the same priority family, and which are active vs expired) cannot be completed with the required rigor. The claims themselves show what to screen for when building a freedom-to-operate file: processes that form treprostinil salts must demonstrate they do not meet the impurity reduction and ambient stability outcomes, or they must diverge on route constraints like isolation/column chromatography timing.
Screening matrix for potential overlap (based only on the asserted claim text)
| Technical feature to match |
Why it matters to US 11,723,887 |
How a competitor might avoid |
| Salt formation from treprostinil solution |
Claim 1 requires contacting treprostinil solution with base |
Form salt from an isolated treprostinil solid, or a different intermediate state (if not captured) |
| Impurity level in product lower than input |
Claim 1 and claim 8 impose outcome-linked impurity reduction |
Choose conditions where impurity levels do not reduce relative to the specified starting impurity profile |
| Ambient-temperature storage |
Claims 1 and 6 require ambient stability and/or storage |
Use controlled-temperature storage regimes or show instability at ambient |
| Starting impurities from alkylation + hydrolysis |
Claims tie input impurity origin to upstream steps |
Use a different upstream pathway or generate different impurity profile |
| Diethanolamine as base (species) |
Claims 3 and 5/7 lock in diethanolamine salt |
Use another cation/anion base system if the competitor’s goal is outside diethanolamine |
| No column chromatography between alkylation and hydrolysis |
Claim 9 locks a specific route constraint |
Insert chromatography between those steps (for that variant) |
| No treprostinil isolation before salt formation |
Claim 10 requires treprostinil not be isolated prior to salt formation |
Isolate treprostinil before salt formation |
| Batch size threshold |
Claim 1 requires >= 2.9 grams |
Keep covered batch size below 2.9 g (if manufacturing strategy allows) |
Claim-by-claim structured map
| Claim |
Coverage type |
Core limitation(s) |
Strongest narrowing points |
| 1 |
Product-by-process (salt batch) |
Ambient-storable treprostinil salt; starting treprostinil has alkylation/hydrolysis impurities; solution to base salt; impurity reduction; batch >= 2.9 g |
Outcome impurity reduction + ambient stability + >=2.9 g |
| 2 |
Dependent |
Vacuum dried |
Requires vacuum drying |
| 3 |
Dependent |
Base is diethanolamine |
Species: diethanolamine salt |
| 4 |
Composition (finished product) |
Carrier + therapeutically effective amount; salt comes from claim 1 batch |
Derivative on claim 1 batch origin |
| 5 |
Dependent |
Diethanolamine salt in claim 4 |
Species: diethanolamine salt in formulation |
| 6 |
Method |
Store salt batch at ambient temp then prepare product |
Adds time-sequence requirement |
| 7 |
Dependent |
Diethanolamine salt in claim 6 |
Species |
| 8 |
Process (route) + impurity reduction mechanism |
Alkylate benzindene triol; hydrolyze to treprostinil solution; form treprostinil salt with base; store salt ambient; acidify to treprostinil; salt formation reduces impurities from steps (a) and/or (b) |
Route definition + impurity reduction tied to salt formation |
| 9 |
Dependent |
No column chromatography between steps (a) and (b) |
Route handling constraint |
| 10 |
Dependent |
Treprostinil in (b) not isolated before (c) |
Intermediate handling constraint |
| 11 |
Product-by-process |
Treprostinil made by method of claim 8 |
Captures treprostinil itself after salt storage and acidification |
What is the business-grade takeaway on scope and enforceability?
- The patent is enforceable across both batch manufacturing and finished formulation because claim 4 and claim 6 tether the final product to the covered salt batch and its ambient-storage step sequence.
- The enforceable core is not just “make a salt.” It is “make an ambient-stable salt batch that reduces impurities relative to a specific impurity-bearing starting treprostinil derived from alkylation/hydrolysis.”
- Dependent claims create multiple fallback positions: diethanolamine salt, vacuum drying, and route constraints (no chromatography, no isolation before salt formation).
- Claim 8 adds a mechanistic/process narrative that can broaden proof at litigation: impurity reduction is linked to the salt formation step (c) after alkylation (a) and hydrolysis (b), then storage, then acidification.
Key Takeaways
- US 11,723,887 claims ambient-temperature-storable treprostinil salt batches produced by converting an impurity-bearing treprostinil solution to a salt via a base, with lower impurity levels than the starting treprostinil input and a batch size >= 2.9 g (claim 1).
- The enforcement surface spans finished formulations (carrier + therapeutically effective dose) where the salt originates from the covered claim 1 batch (claims 4-5) and storage-then-manufacture workflows (claims 6-7).
- The process landscape embedded in the claim text is specific: benzindene triol alkylation followed by hydrolysis to treprostinil solution, then salt formation, ambient storage, and acidification back to treprostinil (claim 8).
- Dependent claim fallbacks narrow material alternatives and process design choices: diethanolamine (claims 3, 5, 7), vacuum drying (claim 2), no column chromatography between steps (claim 9), and no isolation before salt formation (claim 10).
FAQs
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Does the patent require diethanolamine to be used?
No. Claim 1 covers a treprostinil salt formed with “a base.” Diethanolamine is specifically claimed in dependent claims 3, 5, and 7.
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Is ambient storage required for the salt batch itself or only for the method of preparing the product?
Both. Claim 1 requires a batch “can be stored at ambient temperature,” and claim 6 requires a method that includes storing the batch at ambient temperature before preparing the product.
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What role does “impurity reduction” play?
It is a core limitation in claim 1 (impurities in the starting treprostinil are lower in the pharmaceutical batch) and claim 8 (forming the salt reduces impurities resulting from alkylation/hydrolysis).
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Can the claims be avoided by isolating treprostinil prior to salt formation?
Claim 10 narrows embodiments to cases where treprostinil from hydrolysis (b) is not isolated before contacting with base (c). If isolation occurs, that dependent claim path may not apply, but claim 1 can still be implicated depending on how the process aligns.
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Does the patent protect the treprostinil free base as well?
Yes, via a product-by-process claim 11 covering treprostinil prepared by the claim 8 method (ambient-stable salt storage followed by acidification).
References
[1] United States Patent and Trademark Office. US 11,723,887. Claims as provided in the prompt.
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