United States Patent 5,214,052: Claim Scope, Patent Term and Pharmaceutical Formulation Landscape

United States Patent 5,214,052 protects a solvent system and injectable pharmaceutical composition for an N2-arylsulfonyl-L-argininamide or its salt. The patent does not broadly claim the active compound, its therapeutic use, or every formulation containing the compound. Its enforceable scope is limited to formulations containing ethanol, water, and a saccharide, plus narrower embodiments using sorbitol, glucose, glycerin, or sucrose.

The patent issued on May 25, 1993. Its ordinary pre-1995 U.S. patent term therefore ended on May 25, 2010, absent an unusual terminal-disclaimer or term adjustment issue. It is no longer an active barrier to U.S. generic manufacture, formulation, or marketing. [1, 2]

What does United States Patent 5,214,052 protect?

The patent has two principal claim categories:

Claim	Subject matter	Required elements	Scope
1	Dissolution method	N2-arylsulfonyl-L-argininamide or salt; ethanol; water; saccharide	Broad process claim
2	Preferred dissolution method	Claim 1 plus sorbitol, glucose, glycerin, or sucrose	Narrower process claim
3	Injectable composition	N2-arylsulfonyl-L-argininamide or salt; ethanol; water; saccharide	Broad composition claim
4	Preferred injectable composition	Claim 3 plus sorbitol, glucose, glycerin, or sucrose	Narrower composition claim

The invention is a formulation technology. It addresses dissolution or formulation of the specified argininamide compound in an aqueous injectable vehicle that also contains ethanol and a saccharide.

The patent does not, based on the supplied claims, claim:

The N2-arylsulfonyl-L-argininamide molecule by itself
A salt of the compound without the specified solvent system
Ethanol-free formulations
Water-free formulations
Saccharide-free formulations
Oral, transdermal, inhaled, or topical dosage forms
A therapeutic indication
A specific dose or concentration
A specific pH
A specific ethanol-to-water ratio
A particular manufacturing sequence
A lyophilized product unless the final claimed composition contains the required components
A product containing only one of the three required vehicle classes

The chemical structure designated “formula (I)” is essential to the analysis. The claim text supplied does not reproduce the structural image. Accordingly, the exact aryl substituents, salt forms, stereochemical limitations, and chemical boundaries of formula (I) cannot be independently mapped from the text alone. The formulation analysis below applies to the patent-defined compound or compound class.

How should claim 1 be construed?

Claim 1 is a method claim requiring dissolution of the covered active ingredient in a solvent containing ethanol, water, and a saccharide.

What are the mandatory elements of claim 1?

A potentially infringing process would need to include all of the following:

A step of dissolving the relevant N2-arylsulfonyl-L-argininamide.
The compound in its free form, its salt, or both.
A solvent containing ethanol.
Water in the solvent.
A saccharide in the solvent.

The term “comprising” generally makes the claim open-ended. A formulation may contain additional solvents, buffers, preservatives, tonicity agents, stabilizers, or excipients without falling outside the claim solely because those additional ingredients are present.

The claim does not specify minimum quantities. A formulation containing very small but technically meaningful amounts of ethanol, water, and a qualifying saccharide could raise a literal-scope issue if the active ingredient falls within formula (I) and the components perform the claimed dissolution function.

Does claim 1 require an injectable product?

No express injection limitation appears in claim 1. It is directed to a method for dissolving the active ingredient. The specification may provide an injectable context, but claim 1 as quoted does not require administration by injection.

A noninjectable dissolution process could therefore fall within the literal wording of claim 1 if every other limitation is satisfied. Claim 3, by contrast, is expressly directed to a pharmaceutical composition for injection.

What does “and/or its salt” cover?

The wording is intended to cover:

The free N2-arylsulfonyl-L-argininamide
A salt of that compound
A formulation containing both forms

The exact salts remain subject to the chemical disclosure and claim construction principles applicable to the patent. The phrase does not automatically cover unrelated salts, derivatives, prodrugs, metabolites, or analogs outside formula (I).

How should claim 2 be construed?

Claim 2 depends on claim 1 and narrows the saccharide limitation. The saccharide must be at least one of:

Sorbitol
Glucose
Glycerin
Sucrose

Because claim 2 depends on claim 1, it retains every limitation of claim 1. The product or process must still include the covered argininamide or salt, ethanol, and water.

The phrase “at least one member selected from the group” permits use of:

One listed excipient
More than one listed excipient
All four listed excipients

Glycerin is chemically a polyol rather than a conventional carbohydrate saccharide. That distinction does not remove it from claim 2 because the claim expressly lists glycerin. The issued claim language controls the scope of the limitation.

What does claim 3 protect?

Claim 3 is a composition claim for injection containing:

The formula (I) N2-arylsulfonyl-L-argininamide or its salt
Ethanol
Water
A saccharide

The claim is broader than claim 4 because it does not limit the saccharide to the four named substances.

The claim likely reaches a liquid injectable product in which the active ingredient is dissolved or maintained in solution. The quoted text does not require a particular concentration, container, vial, ampoule, dosage volume, sterility specification, or administration route beyond the claim’s “for injection” characterization.

What formulations are potentially outside claim 3?

A formulation may avoid the literal elements of claim 3 if it lacks any one required component, such as:

No ethanol
No water
No saccharide
A different active compound outside formula (I)
A derivative or prodrug rather than the claimed argininamide
A solid product that is not a composition for injection and does not contain the claimed solvent system

A formulation containing ethanol, water, and a nonlisted excipient may still fall within claim 3 because the claim is open-ended.

What does claim 4 add?

Claim 4 limits claim 3 to formulations using sorbitol, glucose, glycerin, sucrose, or a combination of those ingredients.

The claim does not require all four. A product containing ethanol, water, and sorbitol would satisfy the excipient limitation if the active ingredient is within formula (I). A product using mannitol, lactose, or another saccharide without one of the four listed substances may fall outside the literal scope of claim 4, while still potentially implicating claim 3.

How strong is the patent estate for United States Patent 5,214,052?

Claim-strength assessment

Issue	Assessment	Reason
Chemical compound protection	Weak or absent	The supplied claims do not claim the active compound alone
Formulation specificity	Moderate	All claims require ethanol, water, and a saccharide
Breadth of excipient language	Broad in claims 1 and 3	“Saccharide” is not limited to the four named excipients
Preferred-excipient protection	Narrow in claims 2 and 4	Limited to sorbitol, glucose, glycerin, or sucrose
Concentration limitations	Broad	No numerical concentration appears in the supplied claims
pH and buffer protection	Absent from the claims	No pH or buffer limitation is recited
Manufacturing-process protection	Limited	Claim 1 requires dissolving but does not prescribe a detailed process sequence
Current exclusionary value	None in the United States	The ordinary patent term expired in 2010

The strongest technical feature is the combination of ethanol, water, and a saccharide. The strongest commercial feature during the patent term was likely the ability to cover a ready-to-use or reconstituted injectable formulation without claiming the active pharmaceutical ingredient itself.

The estate was narrower than a compound patent and potentially easier to design around. A competitor could have pursued an alternative solvent system, a nonaqueous formulation, a different solubilization technology, or a different chemical form of the active ingredient, subject to other patents and regulatory requirements.

When did United States Patent 5,214,052 lose exclusivity?

The patent issued May 25, 1993. For a U.S. application subject to the pre-June 8, 1995 patent-term rules, the ordinary term was 17 years from issuance. The ordinary expiration date was therefore May 25, 2010. [1, 2]

Event	Date
Patent issued	May 25, 1993
Ordinary 17-year term endpoint	May 25, 2010
Current status	Expired by term

The expiration analysis concerns patent enforceability, not regulatory exclusivity. FDA marketing exclusivity, if any existed for the underlying product, would have been a separate protection under the Federal Food, Drug, and Cosmetic Act. Patent expiration does not itself establish the expiration date of FDA exclusivity. [3]

What is the Orange Book status of the patent?

The claims are directed to a formulation and dissolution method. A patent of this type could potentially be listed in the FDA Orange Book only if it met the statutory and regulatory criteria for a patent claiming an approved drug substance, drug product, or method of use. FDA listing rules do not treat every patent relating to a pharmaceutical product as automatically listable. [4]

The supplied information does not establish that U.S. Patent 5,214,052 was listed in the Orange Book for a specific reference-listed drug. The patent number alone is therefore not evidence of an Orange Book-listed patent, a current Paragraph IV dispute, or a regulatory block on ANDA approval.

Because the patent expired in 2010, any historical Orange Book listing would no longer create a live patent-term barrier. A listed expired patent can remain relevant to historical litigation or regulatory records, but it does not support a current injunction based on the expired term.

Were Paragraph IV challenges relevant?

A Paragraph IV certification is relevant when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. [3, 5]

For this patent:

A Paragraph IV challenge could have been relevant during the patent’s active term if the patent was listed for the applicable reference product.
A formulation-focused ANDA applicant would have had to assess whether its product contained the claimed active ingredient, ethanol, water, and saccharide.
A design-around product lacking one required component could support a noninfringement position.
After May 25, 2010, the patent could no longer support a conventional patent-based delay of ANDA approval.
A current generic applicant would not normally need a Paragraph IV strategy directed to an expired patent, although historical certification records may still appear in FDA or litigation files.

No current Paragraph IV risk can be inferred from the patent number alone.

What generic launch risks exist today?

The patent creates no current U.S. launch risk based on its expired term. The relevant risks have shifted from this patent to:

Other active formulation patents
Drug-substance or process patents
Patent rights covering a specific salt or polymorph
Method-of-use patents
Regulatory exclusivity
Injectable manufacturing controls
Sterility and container-closure requirements
Supply-chain access to the active ingredient
Clinical and bioequivalence requirements for the applicable dosage form

For an injectable product, formulation design-around may still require extensive development work. The absence of a live patent does not eliminate technical barriers associated with solubility, stability, precipitation, compatibility, sterilization, and container interaction.

Does biosimilar risk apply?

No. Biosimilar rules apply to biological products, not conventional small-molecule argininamide formulations. [6]

A product covered by these claims would ordinarily be evaluated through an abbreviated new drug application or another small-molecule pathway, depending on the active ingredient, dosage form, and reference-product status. The primary competitive threat would be generic, not biosimilar, entry.

What licensing deals or litigation affect the patent?

The claims supplied do not identify a license, settlement, assignment, terminal disclaimer, or litigation matter. The patent itself establishes the technical claim scope and original ownership information recorded by the USPTO, but a patent document alone does not establish the commercial terms of any license or settlement.

Because the patent expired in 2010, any historical litigation or settlement would have limited current exclusionary value unless it created separate contractual restrictions, admissions, or rights concerning other patents. A settlement involving this patent would not revive the expired patent term.

How does this patent compare with a compound or method-of-use patent?

Patent type	Typical protected subject matter	Relative value during active term	Current relevance here
Compound patent	Active molecule or defined chemical genus	Usually strongest	Not established by claims 1-4
Salt or polymorph patent	Specific solid or salt form	Moderate to strong	Not established by claims 1-4
Formulation patent	Vehicle, concentration, stability, or delivery system	Product-specific	This patent category
Method-of-use patent	Treatment of a defined disease or patient group	Depends on labeling and use	Not present in supplied claims
Manufacturing patent	Synthesis, purification, or isolation	Can create supply barriers	Not present in supplied claims
Injectable composition patent	Parenteral formulation	Narrower but commercially relevant	Claims 3 and 4

The patent’s value was concentrated in injectable formulation protection rather than molecule ownership. Its expired status removes the current legal barrier, but its claim structure remains relevant for freedom-to-operate reviews of historical products and patent-family analysis.

Key Takeaways

United States Patent 5,214,052 claims a formulation platform for an N2-arylsulfonyl-L-argininamide or its salt.
Claims 1 and 2 are dissolution-method claims.
Claims 3 and 4 are injectable-composition claims.
Every independent claim requires ethanol, water, and a saccharide.
Claims 2 and 4 narrow the saccharide to sorbitol, glucose, glycerin, or sucrose.
The patent does not, based on the supplied claims, claim the active compound, a therapeutic indication, or a specific concentration.
The patent issued May 25, 1993, and its ordinary 17-year term ended May 25, 2010.
The patent is not a current U.S. barrier to generic entry.
Biosimilar risk does not apply because the claimed subject matter concerns a small-molecule pharmaceutical formulation.
Current commercial risk must be assessed against later patents, Orange Book records, regulatory exclusivity, and manufacturing constraints.

FAQs

Does United States Patent 5,214,052 claim sorbitol formulations?

Yes. Claims 2 and 4 expressly identify sorbitol as a permitted saccharide. A covered formulation would also need the claimed argininamide or salt, ethanol, and water.

Can a formulation using glucose avoid claim 4?

No, not on the basis that glucose is not listed. Glucose is expressly included in claim 4. The formulation would need to avoid another claim element to establish a noninfringement position.

Does a saline formulation infringe the patent?

Not necessarily. Saline alone does not satisfy the quoted ethanol and saccharide limitations. A saline formulation containing ethanol, water, a qualifying saccharide, and the claimed active compound could present a different result.

Is the patent relevant to a product containing only the active ingredient?

No, not under the supplied claims. The claims require a solvent or composition containing ethanol, water, and a saccharide.

Can an expired formulation patent block FDA approval?

No. An expired patent cannot provide a current patent-based stay or injunction. FDA approval may still depend on other patents, regulatory exclusivity, product-specific requirements, and applicable ANDA certifications.

References

United States Patent and Trademark Office. (1993). United States Patent No. 5,214,052.
35 U.S.C. § 154. Patent term.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 355(j), 355(c).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
21 C.F.R. § 314.101. ANDA submission and patent certifications.
Biologics Price Competition and Innovation Act, 42 U.S.C. § 262.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	62-188484	Jul 28, 1987

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Germany	122005000056	⤷ Start Trial
Germany	3866303	⤷ Start Trial
European Patent Office	0301970	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,214,052

Summary for Patent: 5,214,052