Patent 11,147,817 Claim Scope and U.S. Landscape for Pemetrexed Liquid Formulations With L‑Cysteine, Low O2, and No Chelators

United States Patent 11,147,817 (pemtrexed liquid composition with L‑cysteine, ultra-low headspace/dissolved oxygen, <1% w/w total impurities, no chelating agent) is built around a tight formulation and process control strategy. The independent claim is constrained by five quantitative guardrails (pemetrexed concentration, oxygen limits, total impurities, absence of chelating agent, and impurity stability for at least one month at room temperature). Dependent claims narrow by excipient selection, specific “no chelator” scope, and sterilization (steam with defined F0 range). The most meaningful freedom-to-operate (FTO) signal for competitors is that variants that keep the same oxygen/impurity targets but swap chelator type, oxygen control strategy, or sterilization method may or may not remain within the literal claim boundaries, depending on how “chelator” and “total impurities” are interpreted.

What does US Patent 11,147,817 claim for pemetrexed liquid drugs in the U.S.?

Core independent claim (Claim 1) captures a specific pemetrexed liquid composition with:

Dose range: 5 mg/mL to 100 mg/mL pemetrexed (or pharmaceutically acceptable salt)
Stabilizer: L‑cysteine (or salt)
Excipient: any pharmaceutically acceptable excipient
Headspace oxygen: <5% v/v headspace oxygen
Dissolved oxygen: <2 ppm dissolved oxygen
Impurities: <1% w/w total impurities
No chelating agent: composition “does not contain a chelating agent”
Stability/time: total impurities remain <1% w/w for at least one month at room temperature

Infringement map (literal) for Claim 1

A generic or follow-on manufacturer must make a liquid pemetrexed that includes L‑cysteine, meets oxygen control thresholds, has low impurities at release and after 1 month at room temperature, and has no chelator present (as that term is construed in the patent).

Material constraint

Claim 1 is not just composition. The stability requirement ties composition identity to an empirical performance outcome. That tends to increase enforceability against products that cannot demonstrate matching impurity stability under the claimed storage condition.

How do dependent claims narrow the formulation scope beyond Claim 1?

What excipients are allowed (Claim 2) and how does it affect “open” claim scope?

Claim 2 states the pharmaceutically acceptable excipient is chosen from:

osmolarity adjusting agent
stabilizing agent
pH adjusting agent
vehicle
combinations

This is a permitted-excipient list but still broad in practice because many liquid pharmaceutical components fit these categories. The risk to design-around is lower if a competitor already uses these excipient classes. The bigger risk remains the oxygen/impurity/no-chelator combination.

What chelators are explicitly contemplated (Claims 3 and 9) even though Claim 1 says “no chelating agent”?

Claims 3 and 9 list chelating agents as a selection:

EDTA (ethylene diamine tetraacetic acid) or salt
DTPA (diethylene triamine pentaacetic acid) or salt
calteridol or salt
combinations

This creates a claim-interpretation tension:

Claim 1 and the corresponding claim sets state “does not contain a chelating agent.”
Yet dependent claims define chelators that appear as “selected from” lists under a dependent numbering structure.

Net effect (practical): competitors are put on notice that these specific chelators are treated as “chelating agents” in the patent’s technical context. Even if the dependent structure is drafted inconsistently (common in complex claim sets), it strengthens an argument that substituting EDTA/DTPA/calteridol is not a safe design-around route and that “chelator” is construed to include those entities.

What sterilization method and F0 limits are claimed (Claims 4-5 and Claim 12)?

Claim 4: prepared using terminal sterilization
Claim 5: terminal sterilization is steam sterilization with F0 from 1 minute to 30 minutes
Claim 12 (process): steam sterilization with F0 1-30 minutes of the filtered solution

If a product is non-terminally sterilized or uses an F0 outside 1-30, it may escape the sterilization-dependent coverage. However, Claim 1 still covers the final composition regardless of how it was sterilized, unless the claims are construed as requiring terminal sterilization for composition infringement (the independent claim text you provided does not include that limitation).

What quantitative “at-issue” thresholds are most likely to determine infringement?

Oxygen control

Head space oxygen <5% v/v
Dissolved oxygen <2 ppm

These are tight. They likely correspond to specific fill-batch handling:

oxygen-reduced solutions
nitrogen sparging / degassing
low-oxygen environment during filling
vial/closure selection and headspace control

For infringement, measurement methodology matters (ppm dissolved oxygen and % v/v headspace oxygen are typically test-method dependent), but the claim text hard-codes the numeric thresholds.

Impurity profile

<1% w/w total impurities (and optionally <0.5% w/w in Claims 6 and 10)
impurity stability: remain <1% w/w for at least one month at room temperature

No chelator

“does not contain a chelating agent”
explicit examples in dependent claims: EDTA, DTPA, calteridol

This is a likely design-around hinge:

exclude any chelator, or ensure that any trace metal-binding species are not considered “chelating agents” under claim construction
challenge could arise if excipients or buffers incidentally bind metals

What is covered in the “about 10 mg/mL” and “about 1 mg/mL” specific exemplified compositions (Claims 7-10 and 17-18)?

Two parallel sets anchor at:

pemetrexed ~10 mg/mL
L‑cysteine hydrochloride ~1 mg/mL (Claims 7-8 and 17-18)

Both preserve:

headspace oxygen <5% v/v
dissolved oxygen <2 ppm
<1% w/w total impurities (with optional <0.5% in Claims 10)
no chelating agent
stability at least one month at room temperature (Claims 17-18 explicitly)

These narrower claims create additional coverage for a common formulation target. If a competitor tries to “sit outside” Claim 1 by using pemetrexed concentration near 10 mg/mL but changes oxygen/impurity/chelators, coverage may still remain. If the competitor changes pemetrexed concentration materially outside 5-100 mg/mL, Claim 1 may be avoided, but Claim sets are still likely to exist as variations.

What is claimed about the manufacturing process (Claim 11-13) and how does it relate to composition infringement?

Claim 11 claims a process:

Prepare mixture with:

5 mg/mL to 100 mg/mL pemetrexed
L‑cysteine
excipient
<1% w/w total impurities, while maintaining dissolved oxygen ≤2 ppm

Filter and fill a vial, maintaining:

headspace oxygen <5% v/v to produce the liquid composition

Claim 12 adds:

steam terminal sterilization F0 1-30 minutes

Claim 13 narrows impurity:

mixture comprises <0.5% w/w total impurities

Business implication

Even if a competitor tries to reach a matching composition, they can face separate process infringement if their manufacturing achieves the same oxygen-management steps and filling conditions and yields the claimed impurity performance.

Does the patent claim pH ranges, and what does that mean for formulation design? (Claims 14-16)

Claim 14: pH between 6 and 8
Claim 15: pH about 7.4
Claim 16: Claim 7 dependent also pH between 6 and 8

These are typical for pharmaceutical stability and compatibility. If a competitor keeps oxygen/impurity/no-chelator requirements but uses pH outside 6-8, they may aim to avoid these dependent claim coverage. The independent Claim 1 you provided does not include pH limits, so pH changes alone do not necessarily avoid infringement.

What patent landscape does this claim set likely overlap in the pemetrexed liquid and oxygen-stabilized formulation space?

Landscape theme: reduced oxygen + thiol (L‑cysteine) + low impurities

The claim architecture reads like an improvement to commercially deployed pemetrexed liquid presentations where oxidation-related degradation and metal-catalyzed pathways drive impurities. By combining:

L‑cysteine (a reducing/antioxidant thiol)
low headspace and low dissolved oxygen
no chelator
a quantified impurity retention over one month

…the patent targets both the chemical and packaging/process oxygen vectors.

Where competitors are vulnerable

If competitors use chelator-free systems with L‑cysteine and reach the same oxygen and impurity thresholds, they land directly inside Claim 1.
If competitors use chelators (EDTA/DTPA/calteridol or similar), they may avoid the “no chelating agent” limitation but risk losing thiol-oxygen synergy that the claims presume, affecting impurity specs and stability.
If competitors keep chelator out but do not reach <2 ppm dissolved oxygen or <5% v/v headspace oxygen, they may avoid literal oxygen limitations but might still infringe if oxygen testing and measurement are interpreted differently.

Likely adjacent patent families

Without bibliographic details beyond this single patent, the most defensible statement from your claim text is that 11,147,817 sits in the class of:

formulation patents for pemetrexed liquid dosage forms
oxygen-controlled storage/packaging strategy
thiol-based stabilization strategies

Given the numeric oxygen and impurity retention requirements, it is less likely to be a generic “composition” patent without strong data support, and more likely to be enforceable as a specific manufacturing-quality claim.

Which product types are most exposed: generics, authorized generics, and reformulated versions?

Generics and authorized generics

They are exposed if they:

market a pemetrexed liquid within 5-100 mg/mL
include L‑cysteine (or equivalent thiol not captured by the claim)
keep oxygen below thresholds
eliminate chelators
meet impurity and stability specs

Reformulated “next-gen” versions

A reformulation that changes one element can still be blocked because Claim 1 includes multiple constraints. Practically, it is difficult to avoid all of:

oxygen limits
impurity limits and stability
no chelator

Different sterilization approach

Steam sterilization is only explicitly tied to dependent claims (terminal sterilization, F0 1-30). A competitor could use alternative sterilization while still infringing Claim 1 if the final composition meets all independent limitations.

How strong is the patent estate built on these claims (claim strength and enforcement leverage)?

What strengthens enforceability

Multiple hard numeric limitations (oxygen, impurities, concentrations)
A clear “does not contain chelating agent” negative limitation
A functional stability requirement tied to impurity retention over time and temperature (one month at room temperature)

What creates legal vulnerability

Potential internal drafting tension where dependent claims discuss selecting chelators while the independent claim excludes chelators. This can complicate claim construction, but the explicit lists of EDTA/DTPA/calteridol support a prosecution and litigation record that these are “chelators” for interpretation.

Overall strength assessment from the claim set alone

The claim set is tailored to a specific manufacturing-quality profile rather than a broad conceptual stabilization method. That can enhance validity in litigation if prior art does not disclose the same oxygen/impurity/no-chelator bundle.

What generic entry risks exist if a filer tries to copy the oxygen-stabilized thiol approach but changes chelator status?

A filer’s principal risk is partial non-avoidance:

If a filer adds any chelator-like excipient or metal-binding stabilizer that is deemed a chelating agent, they likely fall outside “no chelating agent” language but may still face validity challenges if they cannot meet impurity stability without chelation.
If a filer removes chelators but uses higher oxygen during processing/fill, they may be outside oxygen limits but must still hit impurity specs and stability.

Because the independent claim includes both oxygen thresholds and impurity stability outcomes, a filer must solve the entire formulation-quality triangle.

Key claim-to-design-around mapping (high value for FTO and litigation strategy)

Design variable	Claim 1 position	Avoids literal infringement if changed?	Practical effect
Pemetrexed concentration	5 to 100 mg/mL	Yes (move outside range)	Hard because dosing and compatibility
L‑cysteine	required	Yes (omit/replace)	Replace may break stabilization/oxygen-impurity performance
Headspace O2	<5% v/v	Yes (raise above)	Typically difficult without changing fill/closure process
Dissolved O2	<2 ppm	Yes (raise above)	Requires less degassing, but likely worsens impurities
Total impurities	<1% w/w	Yes (exceed)	But exceeding may breach product specs and test methods
Impurity stability	<1% for ≥1 month at RT	Yes (fail stability)	Also likely unacceptable commercially
Chelating agent	must be absent	Potentially yes	But trace metal-binding excipients risk “chelator” interpretation
Steam terminal sterilization with F0 1-30	only in dependent/process claims	Yes for those dependent claims	Doesn’t avoid Claim 1 composition coverage

What commercial or regulatory decision points are implicated by this claim set?

Manufacturing qualification: testers must validate dissolved oxygen and headspace oxygen values consistent with the numeric limits.
Release and stability testing: impurity quantification must show <1% w/w and retention after one month at room temperature.
Regulatory comparability: oxygen control and chelator exclusion can change degradation pathways and impurity profiles, affecting CMC and batch consistency.

Key Takeaways

US 11,147,817 is a tightly constrained pemetrexed liquid formulation patent requiring L‑cysteine, very low oxygen (headspace <5% v/v; dissolved O2 <2 ppm), low and stable impurities (<1% w/w for at least one month at room temperature), and absence of chelating agents.
Dependent claims expand coverage through excipient class limitations, specific chelator identities (EDTA/DTPA/calteridol), and terminal steam sterilization with F0 1-30 minutes.
For generic or reformulated entry, design-around is hard because the claims combine oxygen-control and impurity-stability outcomes, not just a single ingredient change.
The strongest infringement hook is the oxygen + impurity stability + no chelator bundle in the independent claim.

FAQs

1) What oxygen metrics are required to meet US 11,147,817’s composition limits?
Headspace oxygen must be <5% v/v and dissolved oxygen must be <2 ppm.

2) Does the patent require terminal sterilization for composition infringement?
Claim 1 as provided does not require terminal sterilization. Steam terminal sterilization with F0 1-30 minutes is tied to dependent/process claims.

3) Can a competitor include a chelator to avoid the “no chelating agent” limitation?
The independent claim excludes chelating agents; dependent claims explicitly treat EDTA, DTPA, and calteridol as chelators. Adding such agents likely avoids the “no chelator” wording but may worsen impurity stability absent the claimed oxygen/thiol strategy.

4) What impurity testing matters most under this patent?
Both release total impurities (<1% w/w) and impurity retention after at least one month at room temperature (<1% w/w).

5) Is pH part of the independent claim?
No pH limitation appears in Claim 1 as provided. pH ranges (6-8, and about 7.4) are in dependent claims.

References

United States Patent Application/Publications and full patent text for US 11,147,817 (claims provided in prompt).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Shilpa	PEMETREXED	pemetrexed disodium	SOLUTION;INTRAVENOUS	215179-003	May 22, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Shilpa	PEMETREXED	pemetrexed disodium	SOLUTION;INTRAVENOUS	215179-001	May 22, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Shilpa	PEMETREXED	pemetrexed disodium	SOLUTION;INTRAVENOUS	215179-002	May 22, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
World Intellectual Property Organization (WIPO)	2016151365	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,147,817

Which drugs does patent 11,147,817 protect, and when does it expire?

Summary for Patent: 11,147,817