United States Drug Patent 5,403,858: Scope, Claims, Expiration, and Taxane Patent Landscape

U.S. Patent No. 5,403,858 covers low-ethanol pharmaceutical compositions containing paclitaxel or docetaxel-type taxanes dissolved in specified surfactants. It also covers diluted perfusions and two manufacturing processes. The patent issued on April 4, 1995, and its 17-year term expired on April 4, 2012, assuming no applicable terminal disclaimer or exceptional term adjustment. It therefore presents no current U.S. exclusivity barrier to generic development.[1]

What does U.S. Patent 5,403,858 protect?

The patent protects formulations rather than a new taxane molecule. Its core technical subject is the preparation of injectable taxane compositions that contain little or no ethanol while maintaining the taxane in a surfactant-based solution.

The claims cover two principal compounds:

Claim embodiment	Taxane identity	Structural designation in supplied claims
Docetaxel-type compound	Docetaxel, also known as Taxotere	R = hydrogen; R1 = tert-butoxycarbonylamino
Paclitaxel-type compound	Paclitaxel, also known as Taxol	R = acetyl; R1 = benzamido or benzoylamino

The supplied text identifies claim 4 as requiring a "benzoyloxyamino radical." That language is chemically inconsistent with the usual paclitaxel structure and with claim 1, which refers to a "benzoylamino radical." The discrepancy may result from transcription or OCR. Claim construction would require review of the issued patent images, specification, prosecution history, and certified claim text.

How broad is claim 1 of Patent 5,403,858?

Claim 1 is the principal composition claim. It requires all of the following:

A compound within the claimed taxane formula.
The compound must have either:
- hydrogen or acetyl at the R position; and
- tert-butoxycarbonylamino or benzoylamino at the R1 position.
The compound must be dissolved in a surfactant selected from:
- polysorbate;
- polyoxyethylene glycol; or
- hydrogenated castor oil.
The composition must be "essentially free of ethanol."
The composition must be a formulation, not merely the taxane compound itself.

The claim does not cover every paclitaxel or docetaxel formulation. A formulation outside the listed surfactant classes would not literally satisfy claim 1. A formulation with a material amount of ethanol could also fall outside the claim, subject to the interpretation of "essentially free of ethanol" and the dependent thresholds in later claims.

The phrase "consisting essentially of" is important. It generally permits additional ingredients that do not materially alter the basic and novel characteristics of the claimed composition. The formulation could therefore contain ordinary pharmaceutical excipients, buffers, water, tonicity agents, stabilizers, or administration-compatible ingredients, unless those ingredients materially change the claimed low-ethanol surfactant formulation.

What concentration ranges are protected?

Claims 5 through 9 narrow the composition by taxane concentration and ethanol content.

Claim	Limitation
5	Up to 200 mg/mL of the taxane
6	20 to 80 mg/mL for the docetaxel-type compound
7	6 to 20 mg/mL for the paclitaxel-type compound
8	Less than 2% ethanol
9	Up to 80 mg/mL, dependent on claim 5

Claims 6 and 7 are commercially relevant because they correspond to concentrated injectable products rather than final infusion solutions. Claim 7 is particularly directed to a paclitaxel concentration range. Claim 6 is directed to a higher docetaxel concentration range.

A product containing 10 mg/mL paclitaxel in polysorbate and less than 2% ethanol would fall within the literal scope of claims 1, 7, and 8 if the remaining limitations were satisfied. A product containing 100 mg/mL docetaxel could fall within claim 5 but not claim 9 or claim 6.

What does independent claim 10 add?

Claim 10 repeats the principal composition concept with an express ethanol limitation of less than 5% by volume. It is independently drafted rather than merely dependent on claim 1.

Its elements are:

a claimed paclitaxel- or docetaxel-type taxane;
dissolution in polysorbate, polyoxyethylene glycol, or hydrogenated castor oil; and
less than 5% ethanol by volume.

The practical difference is that claim 10 provides an independent route to infringement without relying on the phrase "essentially free of ethanol" in claim 1. Claims 11 narrows the threshold to less than 2% ethanol.

What perfusion formulations are protected?

Claims 12 through 14 cover diluted infusion or perfusion solutions.

Claim	Perfusion limitation
12	Less than 0.5 mg/mL of the docetaxel-type compound, less than 1 mL/L ethanol, and less than 15 mL/L surfactant
13	1 mg/mL or less of the paclitaxel-type compound and less than 1 mL/L ethanol
14	0.1 to 0.3 mg/mL of the docetaxel-type compound, with claim 12's ethanol and surfactant limits

These claims are narrower than claims 1 and 10 because they regulate the final diluted perfusion rather than the concentrated pharmaceutical composition.

The formulation would need to satisfy the numerical limits in the administered solution. A concentrate that falls within claim 1 but is diluted into a final infusion containing more than 1 mL/L ethanol would not satisfy claim 12 or claim 13, although it could raise issues under the broader composition claims depending on how the claims are construed.

What manufacturing methods does Patent 5,403,858 cover?

Claims 15 through 17 protect two preparation routes.

Ethanol-assisted dissolution followed by removal

Claim 15 covers:

dissolving the taxane in ethanol;
adding the surfactant; and
removing the ethanol.

Claim 17 specifies evaporation as the removal method.

This is a process claim directed to the manufacturing sequence, not merely the composition. A manufacturer could avoid literal infringement by using a process that never dissolves the taxane in ethanol, assuming the alternative process does not satisfy the other claim limitations or the doctrine of equivalents.

Low-ethanol direct addition

Claim 16 covers slowly adding the taxane to a surfactant solution containing 1% to 2% ethanol by volume.

The "slowly adding" limitation may create proof issues in litigation. Manufacturing records, batch instructions, validation protocols, and operator procedures would be relevant to determining whether the step was performed.

When did U.S. Patent 5,403,858 lose exclusivity?

The patent issued on April 4, 1995. Because it was issued before the post-1995 patent-term transition fully applied, its ordinary U.S. term was 17 years from issuance. The resulting expiration date was April 4, 2012.[1]

Event	Date
U.S. patent grant	April 4, 1995
Ordinary 17-year expiration	April 4, 2012
Current enforceable term	None

The patent is therefore expired and cannot support a present-day U.S. patent infringement action based solely on the claims quoted by the user.

What is the Orange Book status of Patent 5,403,858?

The Orange Book lists patents submitted by sponsors for approved drug products. Listing practices and patent status can change over time, and an expired patent may remain visible historically even though it no longer creates an exclusionary right.[2]

For present commercial analysis, the relevant conclusion is that Patent 5,403,858 cannot block an ANDA applicant through a current unexpired patent term. It may have been relevant to historical abbreviated-approval certifications, but it is not a current patent barrier for paclitaxel or docetaxel entry.

An applicant today would focus on any later-expiring patents listed for the specific reference product, including formulation, method-of-use, device, or polymorph patents. Patent 5,403,858 itself does not provide current Orange Book exclusivity.

Were Paragraph IV challenges or patent litigation associated with this patent?

A Paragraph IV certification would have been relevant only while the patent was listed and unexpired against an FDA reference product. A Paragraph IV challenge to an expired patent has no practical ability to delay approval based on the patent term.

The historical litigation landscape for paclitaxel and docetaxel was broader than this patent. It included disputes involving:

paclitaxel supply and formulation rights;
Bristol-Myers Squibb's Taxol-related rights;
Sanofi's Taxotere-related rights;
generic injectable formulation approvals; and
later formulation and delivery technologies.

No current litigation risk arises from U.S. Patent 5,403,858 because its term has ended. Any historical settlement involving this patent would have no continuing exclusionary effect unless it contained independent contractual restrictions, which cannot be inferred from the patent record.

Which companies were commercially exposed to this patent?

The main commercial products implicated by the technical subject matter were:

Product or product class	Active ingredient	Relevant formulation issue
Taxol and generic paclitaxel injection	Paclitaxel	Conventional products commonly use polyethoxylated castor oil and substantial ethanol
Taxotere and generic docetaxel injection	Docetaxel	Concentrated surfactant-based formulations, with product-specific diluent and ethanol characteristics
Alternative taxane injections	Paclitaxel or docetaxel	Potentially within the claims if the specified surfactant and ethanol limits are met

The conventional Taxol formulation contains Cremophor EL, a polyethoxylated castor-oil surfactant, and dehydrated alcohol. Its high ethanol content generally places it outside the less-than-5% composition limitation.[3]

Docetaxel products use polysorbate 80-based concentrates. Whether a particular product falls within claims 1, 10, or the perfusion claims depends on the ethanol content, the concentrate or diluted solution being analyzed, and the exact surfactant composition.[4]

How strong was the patent estate?

The patent was technically meaningful but commercially narrow in several respects.

Strength factor	Assessment
Active ingredient coverage	Covers paclitaxel and docetaxel-type embodiments, but not all taxanes
Formulation coverage	Limited to three defined surfactant categories
Ethanol limitation	Narrows the field and creates design-around opportunities
Concentration claims	Provides useful subranges for concentrates and perfusions
Process coverage	Covers ethanol-assisted preparation and a low-ethanol addition process
Duration	Expired in 2012
Current enforcement value	None in the United States

The strongest historical position was against a low-ethanol formulation using one of the listed surfactants and a covered taxane. The estate was weaker against formulations using different solubilizers, alternative delivery systems, substantially different ethanol concentrations, or non-solution dosage forms.

The claims also have technical vulnerabilities:

the missing structural formula in the supplied claim text prevents complete claim mapping;
the "benzoyloxyamino" wording in claim 4 may create an ambiguity;
"essentially free of ethanol" is less precise than the numerical thresholds in claims 2, 8, and 11;
the surfactant terms may require chemical interpretation;
process claims 15 through 17 depend on evidence regarding manufacturing operations.

These issues would have mattered in validity and infringement disputes before expiration. They have no practical effect on current U.S. freedom to operate under this patent.

What generic launch risks exist today?

Patent 5,403,858 creates no current generic launch risk. Paclitaxel and docetaxel are established small-molecule products with multiple approved generic manufacturers and no biosimilar pathway requirement.[3][4]

Current launch analysis should instead focus on:

later-expiring patents listed for the relevant reference product;
injectable formulation patents;
manufacturing-process patents;
drug-master-file controls over critical excipients;
supply of high-purity paclitaxel or docetaxel;
FDA quality requirements for sterile injectable products;
state and federal procurement competition; and
product-specific patent certifications in the Orange Book.

The patent has no geographic force outside the United States. Foreign family members would need separate status analysis in each jurisdiction. Expiration of the U.S. patent does not establish expiration of corresponding European, Canadian, Japanese, or other national rights.

What licensing deals affected the patent?

The patent record alone does not establish a patent-specific license, assignment, or settlement agreement governing current commercialization. The commercial history of paclitaxel and docetaxel involved sponsor relationships and product rights, but those arrangements should not be treated as licenses to Patent 5,403,858 without an executed agreement or a documented transaction filing.

Because the patent expired, any historical license is unlikely to restrict ordinary U.S. commercialization today unless it contains surviving contractual terms unrelated to patent exclusivity.

How does Patent 5,403,858 compare with molecule and product patents?

Patent type	Typical protection	Relevance today
Taxane compound patent	The active molecule or chemical class	Generally expired for paclitaxel and docetaxel
Patent 5,403,858	Low-ethanol surfactant formulation, perfusion, and manufacturing process	Expired April 4, 2012
Product-specific formulation patent	Solubilizer, concentration, dosage form, or stability system	Must be checked by product and jurisdiction
Method-of-use patent	Treatment regimen, cancer indication, or combination therapy	May remain relevant only if separately unexpired and listed
Biosimilar patent	Biologic product and manufacturing estate	Not applicable to these small molecules

Key Takeaways

U.S. Patent 5,403,858 covers low-ethanol formulations of paclitaxel- and docetaxel-type taxanes.
The core limitations are the taxane structure, one of three surfactant categories, and restricted ethanol content.
Claims 12 through 14 cover diluted perfusions; claims 15 through 17 cover specific manufacturing methods.
The supplied claim text contains a likely chemical transcription issue in claim 4.
The patent issued April 4, 1995, and its ordinary term expired April 4, 2012.
It presents no current U.S. patent exclusivity or Paragraph IV launch barrier.
Paclitaxel and docetaxel are small molecules, so biosimilar analysis does not apply.
Current diligence should focus on later product-specific formulation, manufacturing, and method-of-use patents.

FAQs About U.S. Patent 5,403,858

Does Patent 5,403,858 cover paclitaxel itself?

No. It covers selected formulations containing paclitaxel-type and docetaxel-type compounds. It does not claim paclitaxel as a standalone chemical entity.

Does the patent cover Taxol injection?

Only if the specific Taxol formulation satisfies every claim limitation, including the ethanol threshold and listed surfactant requirement. Conventional Taxol injection generally contains substantial ethanol and would not ordinarily satisfy the low-ethanol claims.

Does the patent cover Taxotere injection?

A Taxotere or generic docetaxel formulation could have fallen within the claims if its taxane, surfactant, ethanol concentration, and formulation process matched the claim language. The patent is now expired.

Can a company still be sued under Patent 5,403,858?

No current U.S. infringement claim can be based on activity occurring after expiration of the patent. Historical infringement claims would be subject to separate limitation and procedural rules.

Is a foreign counterpart still enforceable?

The U.S. expiration date does not determine foreign status. Each national family member requires separate review of its grant date, applicable patent-term law, maintenance status, and any supplementary protection certificate.

References

U.S. Patent No. 5,403,858. (1995). Pharmaceutical compositions containing taxane derivatives. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th ed. The Orange Book. https://www.fda.gov/drugsatfda
U.S. Food and Drug Administration. (2024). Paclitaxel injection prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Docetaxel injection prescribing information. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	91 08527	Jul 8, 1991

PCT Information
PCT Filed	July 03, 1992	PCT Application Number:	PCT/FR92/00624
PCT Publication Date:	January 21, 1993	PCT Publication Number:	WO93/00928

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	147992	⤷ Start Trial
Austria	161193	⤷ Start Trial
Australia	2278792	⤷ Start Trial
Australia	666859	⤷ Start Trial
Canada	2102777	⤷ Start Trial
Canada	2102778	⤷ Start Trial
Czech Republic	280965	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,403,858

Summary for Patent: 5,403,858