Details for Patent: 10,010,537

Which drugs does patent 10,010,537 protect, and when does it expire?

Patent 10,010,537 protects CLEVIPREX and is included in one NDA.

This patent has twenty-six patent family members in seventeen countries.

Summary for Patent: 10,010,537

Title:	Clevidipine emulsion formulations containing antimicrobial agents
Abstract:	Pharmaceutical formulations comprising clevidipine and an antimicrobial agent exhibit a reduced propensity for microbial growth and provide increased convenience to health care workers administering clevidipine-containing formulations to patients.
Inventor(s):	Rajeshwar Motheram, Gregory Charles Williams
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US13/270,004
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,010,537
Patent Claim Types: see list of patent claims	Formulation; Compound;

Patent 10,010,537 Claim Scope and US Patent Landscape for Clevidipine Butyrate Injectable Formulations (EDTA/Phospholipid/Oil/Glycerin/Antioxidant Systems)

US Patent 10,010,537 covers specific clevidipine butyrate injectable formulation compositions built around an oil phase (soybean oil), purified egg yolk phospholipids (as a phospholipid emulsifier), glycerin, and chelation plus optional antioxidant and buffer excipients. The independent claim is a formulation-of-ingredients claim with tight concentration bands for each component and a dependent claim set that further narrows pH. A series of dependent claims swap among alternative stabilizers (EDTA always present in the provided claim set; sodium citrate vs sodium ascorbate; oleic acid replacing one of the buffers; with EDTA maintaining the chelation element). The practical IP risk for entrants is that “around” language and relatively broad ranges (for example, soybean oil 4 to 30% w/v; egg yolk phospholipids 0.2 to 2% w/v; clevidipine butyrate 0.01 to 1% w/v) can be read broadly, but the requirement to use purified egg yolk phospholipids plus the specific pH window (about 6 to about 8.8) in dependent claims can force design-around strategies that change the emulsifier class, eliminate EDTA, or move formulation chemistry outside the disclosed ranges.

Because no bibliographic details, prosecution record, claim dependency chart, or Patent Center/USPTO full text were provided for 10,010,537, the analysis below is constrained to the claim language you supplied and to the claim construction implications that follow from that language alone.

What does US Patent 10,010,537 claim for clevidipine butyrate formulations in the US?

Short answer: It claims clevidipine butyrate injectable compositions that combine (1) a defined concentration of clevidipine butyrate, (2) EDTA at defined chelating levels, (3) soybean oil at defined levels, (4) purified egg yolk phospholipids at defined levels, (5) glycerin at defined levels, and (6) water to fill to the stated volume. Dependent claims further limit pH (about 6 to about 8.8, or about 6 to about 8.5) and replace or add specific excipients: sodium citrate, sodium ascorbate, oleic acid, depending on the claim.

Claim 1 core elements and concentration bands (independent claim)

Claim 1 is a composition claim requiring all listed ingredients:

• Clevidipine butyrate: about 0.01 to about 1% w/v
• EDTA: about 0.001 to about 0.1% w/v
• Soybean oil: about 4 to about 30% w/v
• Purified egg yolk phospholipids: about 0.2 to about 2% w/v
• Glycerin: about 2 to about 3% w/v
• Water: up to 100%

Scope implications

• The claim is not limited by particle size, droplet size distribution, emulsification method, sterilization method, or specific isotonicity agents beyond the provided ingredients. That means a formulation can still fall within the claim even if it is prepared by different manufacturing routes, unless those routes necessarily eliminate one of the required components or drive concentrations outside the bands.
• The claim is sensitive to the presence of purified egg yolk phospholipids. A design-around that switches to a different phospholipid source (for example, hydrogenated phosphatidylcholine, soy-derived phospholipids, synthetic phospholipids) can be positioned to argue “not the same ingredient” because the claim expressly requires purified egg yolk phospholipids, not just “phospholipids.”
• The oil phase is specified as soybean oil. This similarly constrains design-around attempts that substitute other triglycerides/neutral oils.

Dependent claims: pH limitations

• Claim 2: formulation of claim 1 with pH about 6 to about 8.8
• Claim 12 (last provided dependent): formulation of claim 11 with pH about 6 to about 8.5

Scope implications

• Dependent claims create a second fence around pH. If a formulation uses the same ingredient package but is adjusted outside the claimed pH window, it can avoid the dependent claim while potentially still infringing independent claim 1 (if claim 1 has no pH requirement). Your provided independent claim 1 contains no pH limitation.

Claims 3–6: alternative excipient modules while preserving the main scaffold

Claim 3 adds sodium citrate at defined levels, replacing the “other excipient” element found in claim 1:

• Sodium citrate: about 0.005 to about 0.5% w/v

• Maintains: clevidipine butyrate (0.01 to 1% w/v), EDTA (0.001 to 0.1% w/v), soybean oil (4 to 30% w/v), purified egg yolk phospholipids (0.2 to 2% w/v), glycerin (2 to 3% w/v), water to 100% w/v.

• Claim 4: claim 3 pH about 6 to about 8.8

Claim 5 swaps sodium citrate for sodium ascorbate:

• Sodium ascorbate: about 0.01 to about 1% w/v

• Maintains the same scaffold: EDTA + soybean oil + purified egg yolk phospholipids + glycerin + water; clevidipine butyrate range unchanged.

• Claim 6: claim 5 pH about 6 to about 8.8

Scope implications

• These claims are structured as interchangeable “stabilizer/buffer” variants around an identical base. If an accused product includes EDTA + egg yolk phospholipids + soybean oil + glycerin in those bands, it can land within claim 1. If it additionally uses citrate or ascorbate in those ranges, it can be exposed to claims 3 or 5 depending on which excipient is present.

Claims 7–10: oleic acid variants and citrate variants

Claim 7 replaces the citrate/as core excipient with oleic acid:

• Oleic acid: about 0.01 to about 2.0% w/v

• Maintains: clevidipine butyrate (0.01 to 1% w/v), EDTA (0.001 to 0.1% w/v), soybean oil (4 to 30% w/v), purified egg yolk phospholipids (0.2 to 2% w/v), glycerin (2 to 3% w/v), water up to 100%.

• Claim 8: claim 7 pH about 6 to about 8.8

Claim 9 adds sodium citrate alongside oleic acid:

• Oleic acid: about 0.01 to about 2% w/v

• Sodium citrate: about 0.005 to about 0.5% w/v

• Maintains EDTA + soybean oil + egg yolk phospholipids + glycerin + clevidipine butyrate + water to 100%.

• Claim 10: claim 9 pH about 6 to about 8.8

Scope implications

• Claim 9’s combination requirement makes it harder to accidentally infringe if a product uses oleic acid but not citrate (or vice versa). But again, claim 1 can still apply because it does not require citrate, ascorbate, or oleic acid.

Claims 11–12: sodium ascorbate variant with tighter ascorbate band

Claim 11 includes sodium ascorbate at a different band than claim 5:

• Sodium ascorbate: about 0.05 to about 1.0% w/v

• Maintains scaffold: clevidipine butyrate (0.01 to 1% w/v), EDTA (0.001 to 0.1% w/v), oleic acid (0.01 to 2% w/v), soybean oil (4 to 30% w/v), purified egg yolk phospholipids (0.2 to 2% w/v), glycerin (2 to 3% w/v), water up to 100%.

• Claim 12: claim 11 pH about 6 to about 8.5

Scope implications

• If a product uses sodium ascorbate but at a level below about 0.05% w/v, it may avoid claim 11 (but still potentially hit claim 1 if the base scaffold matches).

How broad is the chemical scope of US 10,010,537: ingredient ranges and “about” language

Short answer: The independent claim is broad in two dimensions (oil and emulsifier ranges, plus clevidipine concentration range), but narrow in three ingredient identity constraints: EDTA, soybean oil, and purified egg yolk phospholipids.

Range breadth snapshot (from provided claims)

Ingredient (required in claim 1)	Claimed band (about …)	Scope effect
Clevidipine butyrate	0.01% to 1% w/v	Broad API content coverage
EDTA	0.001% to 0.1% w/v	Chelation level matters; still wide
Soybean oil	4% to 30% w/v	Wide excipient loading range
Purified egg yolk phospholipids	0.2% to 2% w/v	Wide emulsifier range, but fixed ingredient identity
Glycerin	2% to 3% w/v	Narrower band (tight design-around)
Water	to 100%	Standard completion

Design-around pressure points

• Switch phospholipid source or chemistry: replace “purified egg yolk phospholipids” with another phospholipid class or source. This is the strongest lever because the claim requires this specific ingredient.
• Switch oil phase: replace soybean oil with another neutral oil. Again, identity constraint.
• Change chelator: omit EDTA or swap to a different chelator. If EDTA is absent, claim 1 is avoided.
• Shift glycerin concentration: glycerin 2–3% w/v is comparatively tight; moving outside it can reduce infringement risk.
• Adjust pH beyond dependent limits: move outside about 6–8.8 or about 6–8.5 for the dependent claims. Note that independent claim 1 still has no pH term.

What patents and claim overlaps typically exist around clevidipine butyrate lipid formulations with EDTA and phospholipids?

Short answer: In US clevidipine product families, the most frequent claim overlap patterns in lipid injectable programs are (1) emulsifier system composition (phospholipid identity and loading), (2) co-solvents and chelators/antioxidants to mitigate degradation and oxidation, and (3) pH windows for stability. US 10,010,537 is specifically anchored on an EDTA + soybean oil + purified egg yolk phospholipids + glycerin scaffold with optional citrate/ascorbate and oleic acid variants.

Where overlaps likely occur (claim-to-claim mapping logic)

• If other patents claim clevidipine lipid injections using phospholipids, oil excipients, glycerin, and chelators, they typically overlap at the “emulsion system” level.
• If other patents use similar excipients but with different ingredient identity (for example, soy phospholipids vs egg yolk phospholipids), then infringement analysis will turn on whether “purified egg yolk phospholipids” is satisfied literally or under doctrine-of-equivalents arguments.
• If other patents have tighter numeric constraints, then 10,010,537 may serve as a “middle-layer” claim: it can catch products with enough closeness to the disclosed ranges even if they differ from a competitor’s narrower formulation.

When does US Patent 10,010,537 lose exclusivity? (Expiration timing based on patent term rules)

Short answer: No expiration date can be computed from the information provided. A hard exclusivity timeline requires the application filing date, patent issue date, and any terminal disclaimer or patent term adjustment facts, none of which were included.

What Orange Book status exists for products using clevidipine butyrate formulations similar to claim 1?

Short answer: No Orange Book listing, NDA number, or listed patent-to-NDA assignment for US 10,010,537 was provided. Without the FDA Orange Book linkage, it is not possible to map enforcement risk through 505(b)(2)/505(j) pathways.

How strong is the patent estate for US 10,010,537 given its claim structure and dependency?

Short answer: Strength is highest against “exact scaffold” products that use the same emulsifier identity (purified egg yolk phospholipids) and oil identity (soybean oil) plus EDTA within the listed bands. The dependent claims (pH and citrate/ascorbate/oleic acid variants) increase coverage granularity, enabling multiple claim-infringement theories if an accused product matches the stabilizer choice and pH.

Enforcement leverage created by claim dependency

• If a product meets claim 1: it can be asserted regardless of whether it contains citrate, ascorbate, or oleic acid, unless those are required by higher dependent claims not selected for assertion.
• If a product also meets pH: dependent claims 2/4/6/8/10/12 provide additional hooks to narrow the factual disputes (pH measurement, buffer/acid-base balance).
• If a product includes sodium citrate: claims 3/4 and 9/10 target that variant.
• If it includes sodium ascorbate: claims 5/6 and 11/12 target ascorbate variants, with claim 11 specifying a higher ascorbate minimum.

What generic entry risks exist for clevidipine butyrate emulsion products under a Paragraph IV theory?

Short answer: Paragraph IV risk hinges on whether a generic or 505(b)(2) sponsor can engineer around claim 1. The scaffold identity constraints (purified egg yolk phospholipids, soybean oil, EDTA) make “design-by-range” difficult if the product is chemically similar. Design-by-excipient identity (phospholipid source, oil phase, chelator) is the most direct risk reducer, since claim 1 does not just constrain ranges; it requires specific ingredient types.

What formulations are protected by US 10,010,537: citrate vs ascorbate vs oleic acid vs pH

Short answer: The patent protects at least four formulation families around the same emulsion scaffold:

1. Claim 1 base: EDTA + soybean oil + purified egg yolk phospholipids + glycerin + water + clevidipine butyrate (no antioxidant/buffer add-on specified in claim 1)
2. Citrate family: claim 3/4 and claim 9/10
3. Ascorbate family: claim 5/6 and claim 11/12
4. Oleic acid family: claim 7/8 and claim 11/12 (oleic acid with ascorbate)

How does US 10,010,537 compare with typical lipid injectable formulation claim patterns?

Short answer: Compared with many formulation patents that claim broader classes of emulsifiers (for example, “phospholipids” generally), this one locks to purified egg yolk phospholipids and soybean oil, creating a more enforceable identity-based barrier. Compared with patents that claim only API dose and general formulation categories, it also has multi-parameter numeric constraints that can be used to argue non-infringement when an accused product is outside one band (especially glycerin 2 to 3% w/v and EDTA 0.001 to 0.1% w/v).

Key Takeaways

• US 10,010,537 is a formulation-scaffold patent: clevidipine butyrate plus EDTA, soybean oil, purified egg yolk phospholipids, glycerin, and water with specified concentration bands.
• Dependent claims primarily add pH limitations and stabilize-with-excipient variants: sodium citrate, sodium ascorbate, and oleic acid with their own numeric ranges.
• The strongest infringement risk is for products that preserve ingredient identity (egg yolk phospholipids and soybean oil) and remain inside the EDTA and glycerin bands. A generic design-around is more likely to succeed by changing ingredient identities (emulsifier and/or chelator) than by small concentration shifts alone.
• Expiration, Orange Book linkage, and Paragraph IV analysis cannot be performed from the provided information because issue/application dates and FDA patent listing mappings were not included.

FAQs

1. Can a clevidipine formulation infringe claim 2 without infringing claim 1?
   Yes in theory, because claim 2 is dependent on claim 1. If claim 1 is not met, claim 2 cannot be met as dependent, even if pH matches.

2. What ingredient identity is the most critical design-around lever in US 10,010,537?
   Purified egg yolk phospholipids (and separately soybean oil) because they are expressly required ingredients, not just “phospholipids” or “triglycerides.”

3. Does the patent require an antioxidant to fall under claim 1?
   No antioxidant is required by claim 1 as provided. Sodium citrate/ascorbate appear in dependent claims 3/5/9/11.

4. How can an accused product avoid dependent claims if it matches claim 1?
   By adjusting formulation pH outside the dependent ranges (about 6 to about 8.8 or about 6 to about 8.5 for claim 12).

5. If a product uses EDTA but different glycerin concentration, does that avoid infringement?
   It can, if glycerin is moved outside about 2 to about 3% w/v, which would prevent meeting claim 1’s required glycerin range.

References (APA)

1. Provided claim text for US Patent 10,010,537 (user-supplied).

Drugs Protected by US Patent 10,010,537

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Chiesi	CLEVIPREX	clevidipine	EMULSION;INTRAVENOUS	022156-001	Aug 1, 2008		RX	Yes	Yes			Y
Chiesi	CLEVIPREX	clevidipine	EMULSION;INTRAVENOUS	022156-002	Aug 1, 2008		RX	Yes	Yes			Y
Chiesi	CLEVIPREX	clevidipine	EMULSION;INTRAVENOUS	022156-003	Nov 8, 2013		DISCN	Yes	No			Y

International Family Members for US Patent 10,010,537

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011313852
Brazil	112013008601
Canada	2814495
China	103237446