United States Patent 4,386,104: Scope, Claims, Expiration, and Azelaic Acid Patent Landscape

U.S. Patent 4,386,104 covers methods of treating acne with selected C7-C13 dicarboxylic acids, including azelaic acid, through oral, injectable, or topical administration. The patent issued May 31, 1983, and its 17-year pre-URAA term expired May 31, 2000. It is no longer an enforceable barrier to generic or branded azelaic acid products. Current commercial protection depends on later formulation, delivery-system, method-of-use, regulatory, and trademark rights.

What does U.S. Patent 4,386,104 claim?

The patent claims a therapeutic method, not a composition of matter or a pharmaceutical product standing alone.

The independent claim requires each of the following elements:

An individual exhibiting acne.
Administration of a therapeutically effective amount.
Administration in a pharmaceutically acceptable carrier.
Continued administration until acne is reduced or further development is arrested.
Use of at least one covered dicarboxylic acid, derivative, or salt.

The covered acid group includes:

Claimed substance	Carbon count	Commercial relevance
Pimelic acid	C7	Limited
Suberic acid	C8	Limited
Sebacic acid	C10	Limited
Azelaic acid	C9	High
1,9-Nonanedicarboxylic acid	C9	Chemically equivalent to azelaic acid
1,10-Decanedicarboxylic acid	C10	Limited
1,11-Undecanedicarboxylic acid	C11	Limited
Mono- or dimercapto derivatives of the listed acids	C7-C13 parent range	Broad chemical extension
Salts of the listed acids or derivatives	Variable	Potentially broad

The phrase "at least one" permits the use of a single listed acid or a combination of two or more covered acids.

How do claims 2 through 6 narrow claim 1?

Claims 2 through 6 are dependent claims. Each incorporates all limitations of claim 1 and adds a narrower limitation.

Claim	Additional limitation	Practical effect
1	Broad treatment method using listed acids, derivatives, or salts	Core patent scope
2	Oral administration	Covers oral dosage forms
3	Administration by injection	Covers parenteral use
4	Topical administration	Most relevant to azelaic acid creams, gels, and foams
5	Azelaic acid	Species claim directed to azelaic acid
6	1,10-Decanedicarboxylic acid	Species claim directed to decanedioic acid

Claim 5 is commercially more important than claim 6 because azelaic acid became the principal pharmaceutical application of the patent's disclosure.

What is the chemical scope of the patent?

Dicarboxylic acid genus

The patent claims dicarboxylic acids containing from seven to 13 carbon atoms. A dicarboxylic acid has two carboxylic acid groups. The claim language reaches both straight-chain compounds expressly named in the claim and the specified derivatives and salts.

The list is unusual because it identifies azelaic acid and 1,9-nonanedicarboxylic acid separately even though both names refer to the same C9 dicarboxylic acid structure, commonly written as HOOC-(CH2)7-COOH.

The expressly named compounds include:

C7 pimelic acid;
C8 suberic acid;
C9 azelaic acid or nonanedioic acid;
C10 sebacic acid;
C10 decanedioic acid; and
C11 undecanedioic acid.

The claim does not simply cover every dicarboxylic acid with seven to 13 carbon atoms. It uses a closed Markush-style list: the compound must fall within the named group or qualify as a mono- or dimercapto derivative of one of those acids, or as a salt.

Derivatives and salts

The derivative language potentially broadens the claim beyond the free acids. A derivative would still need to retain the claimed relationship to one of the listed dicarboxylic acids and satisfy the method's therapeutic requirements.

Salts may include pharmaceutically acceptable metal, ammonium, or organic-base salts. A salt is not automatically outside the claim merely because it is not administered as the free acid. The method still requires a therapeutically effective amount and an acne-treatment result.

The breadth of this language would have depended on the patent's specification, prosecution history, and the ordinary meaning of "mono or dimercapto derivative" in 1983. The claim text alone does not establish that every chemically modified dicarboxylic acid is covered.

What administration routes are protected?

Topical administration

Claim 4 covers topical use. This is the commercially significant route for azelaic acid products.

A topical cream, gel, foam, lotion, suspension, or similar preparation could implicate claim 4 if it contains a covered acid or salt in a pharmaceutically acceptable carrier and is used to treat acne in the claimed manner.

The claim does not specify:

A particular concentration;
A particular pH;
A specific vehicle;
A particle size;
A penetration enhancer;
A dosing frequency;
A treatment duration measured in days or weeks; or
A particular acne severity.

That omission gives claim 4 broad functional scope, but it also creates potential questions concerning written description, enablement, claim construction, and proof of the claimed therapeutic result.

Oral administration

Claim 2 covers tablets, capsules, solutions, suspensions, and other oral dosage forms containing a covered acid or salt. Oral azelaic acid is less commercially prominent than topical azelaic acid.

Injection

Claim 3 covers administration by injection. This route is not a principal modern commercial pathway for acne treatment and has limited practical relevance to current azelaic acid products.

What are the principal infringement issues?

A product does not infringe merely because it contains azelaic acid. The patent claims a method of use.

For direct infringement, the accused conduct would need to practice every limitation of an asserted claim. For claim 5, the relevant method would generally involve:

Treating a person who has acne;
Using azelaic acid;
Administering it in a pharmaceutically acceptable carrier;
At a therapeutically effective amount; and
Continuing treatment until the acne is reduced or its further development is arrested.

A manufacturer or distributor would not necessarily directly infringe by selling a product without practicing the treatment method itself. Risk could arise through induced infringement if the product labeling, promotional materials, instructions, or other conduct encouraged the claimed acne treatment and the other statutory requirements were satisfied under 35 U.S.C. § 271(b).

The claim is less likely to reach:

Cosmetic use without an acne-treatment indication;
Use for rosacea unless acne treatment is also performed;
Use for hyperpigmentation alone;
Use of an unrelated dicarboxylic acid outside the named group; or
A product that is never administered to an individual exhibiting acne.

When did U.S. Patent 4,386,104 expire?

Event	Date
Patent issued	May 31, 1983
Applicable term regime	Pre-URAA, 17 years from grant
Scheduled expiration	May 31, 2000
Current status	Expired
Current enforceability	None

U.S. patents issued before June 8, 1995 generally received the longer of 17 years from grant or 20 years from the earliest effective U.S. nonprovisional filing date under the transitional rules. For U.S. Patent 4,386,104, the 17-year grant-based term produced an expiration date of May 31, 2000. The patent therefore cannot block current manufacture, sale, labeling, or use of an azelaic acid acne product.

Patent expiration does not erase historical infringement exposure during the enforceable term. It does eliminate prospective exclusionary rights under the patent.

What is the Orange Book status of U.S. Patent 4,386,104?

U.S. Patent 4,386,104 is not a current Orange Book barrier because it expired in 2000.

FDA Orange Book listing rules apply to patents submitted for an approved drug application and require patent information to relate to the approved drug, its formulation or composition, or an approved method of use under 21 C.F.R. § 314.53. A method-of-use patent can be Orange Book relevant when it claims an approved indication. That regulatory mechanism does not revive an expired patent.

Current abbreviated new drug application strategy for an azelaic acid product would therefore not require a Paragraph IV challenge to U.S. Patent 4,386,104. Any current patent certification analysis would focus on later unexpired patents listed against the relevant reference drug.

Does U.S. Patent 4,386,104 create a Paragraph IV risk?

No. A Paragraph IV certification addresses a listed patent that is asserted to be invalid, unenforceable, or not infringed. An expired patent cannot create a current period of Orange Book-based patent exclusivity.

For a modern azelaic acid generic, the relevant risks could include later patents covering:

A specific cream, gel, or foam formulation;
A composition with defined excipients;
A particular concentration or particle size;
A delivery system;
A method for treating a specific acne population;
A method of treating rosacea;
A manufacturing process; or
A combination treatment.

Those later rights must be analyzed separately from the expired 1983 patent.

What later patents protect azelaic acid products?

The post-2000 patent landscape is product-specific. It generally falls into four groups.

Formulation patents

Later patents may protect the physical composition rather than azelaic acid itself. Typical limitations include:

Water-in-oil or oil-in-water emulsions;
Foamable compositions;
Gel systems;
Defined surfactants;
Specific emollients;
Preservative systems;
Particle-size distributions;
Controlled-release vehicles; and
Improved stability or skin penetration.

A generic product can avoid an expired method patent while still infringing a later formulation patent if it reproduces all limitations of the later claim.

Method-of-use patents

Later method patents may target a narrower indication or treatment protocol, such as:

Inflammatory acne;
Noninflammatory acne;
Rosacea;
Post-inflammatory hyperpigmentation;
Defined treatment intervals;
Specific application frequencies; or
Use in combination with another active ingredient.

The scope is generally narrower than claim 1 of U.S. Patent 4,386,104 but can remain commercially important because approved labeling may induce the patented use.

Manufacturing and process patents

Process patents may cover:

Purification of azelaic acid;
Crystallization;
Particle-size control;
Removal of impurities;
Preparation of a specific salt;
Emulsion manufacturing; or
Filling and packaging of a foam or semisolid product.

A process patent can affect active pharmaceutical ingredient sourcing even when the finished product composition is outside a formulation patent.

Regulatory and commercial rights

After the 1983 patent expired, commercial differentiation shifted toward:

FDA approval for specific dosage forms and indications;
Formulation patents;
Trade secrets relating to manufacturing;
Trademarks and trade dress;
Distribution arrangements; and
Market access and payer contracts.

These rights are distinct from the patent estate created by U.S. Patent 4,386,104.

How does this patent compare with modern acne drug patents?

Attribute	U.S. Patent 4,386,104	Modern formulation or product patent
Patent type	Therapeutic method	Composition, formulation, process, or narrower method
Active ingredient	Several C7-C13 dicarboxylic acids	Often azelaic acid in a defined product
Route	Oral, injectable, or topical	Usually a defined dosage form
Concentration	Not specified in claims	Often expressly limited
Carrier	Pharmaceutically acceptable carrier	Specific excipients or vehicle
Expiration	May 31, 2000	Depends on filing date and patent term
Current enforceability	None	Must be assessed patent by patent
Generic relevance	Historical only	Potentially material
Orange Book significance	None today	May be material if listed and unexpired

Compared with patents on retinoids, benzoyl peroxide combinations, topical antibiotics, or dapsone formulations, U.S. Patent 4,386,104 is unusually broad at the active-ingredient and route level but lacks modern formulation detail. Its commercial value ended with patent expiration.

Which companies are challenging the patent?

No current Paragraph IV challenge to U.S. Patent 4,386,104 is commercially relevant because the patent expired more than two decades ago. A generic applicant would not need to overcome this patent through a current Paragraph IV certification.

Any historical litigation involving the patent would have to be evaluated against the May 31, 2000 expiration date. Claims for infringement accruing before expiration are distinct from current generic launch risk.

What generic entry risks exist for azelaic acid products?

The expired patent creates no current blocking risk. The principal risks are product-specific:

A generic may reproduce a protected formulation.
Its labeling may encourage a patented method of use.
Its manufacturing route may fall within a process claim.
Its product may be subject to FDA review delays unrelated to the expired patent.
A reference drug may have unexpired listed patents or regulatory exclusivity.

For azelaic acid, the absence of composition-of-matter protection does not guarantee immediate commercial entry for every dosage form. A generic can be free to use azelaic acid while still needing to design around later claims covering a particular foam, gel, cream, vehicle, or treatment indication.

What is the geographic coverage of the patent?

U.S. Patent 4,386,104 provided rights only in the United States. Patent protection in Europe, Canada, Japan, or other jurisdictions would have required separate national or regional patents.

A U.S. expiration date does not establish the status of foreign family members. Foreign rights may have expired earlier, later, or not issued at all. The U.S. patent itself provides no current geographic exclusionary rights.

How strong is the patent estate today?

The estate created by U.S. Patent 4,386,104 has no current blocking strength because the patent is expired.

Historically, claim 1 had meaningful breadth because it combined:

A broad acne-treatment indication;
Multiple administration routes;
Several dicarboxylic acids;
Derivatives and salts; and
Functional treatment language rather than a narrow formulation.

Its weaknesses included the absence of concentration, dosage, vehicle, and formulation limitations; potential enablement and written-description questions for the derivative and salt language; and the need to prove that the accused conduct practiced the claimed treatment method.

Current patent strength for azelaic acid depends on later patents, not on U.S. Patent 4,386,104.

Key Takeaways

U.S. Patent 4,386,104 claims methods of treating acne with selected C7-C13 dicarboxylic acids, including azelaic acid.
Claim 1 is the core genus claim; claims 2 through 4 address oral, injectable, and topical administration.
Claim 5 specifically covers azelaic acid, while claim 6 covers 1,10-decanedicarboxylic acid.
The patent issued May 31, 1983, and expired May 31, 2000.
It is not a current Orange Book or Paragraph IV barrier.
Current azelaic acid patent risk resides in later formulation, method-of-use, manufacturing, and delivery-system patents.
The patent had U.S.-only territorial scope.
No current revenue or generic-entry protection should be attributed to U.S. Patent 4,386,104.

FAQs About U.S. Patent 4,386,104

Can a company sell generic azelaic acid without licensing U.S. Patent 4,386,104?

Yes. The patent expired on May 31, 2000, so no license is required under this patent.

Does claim 5 cover every azelaic acid product?

No. Claim 5 is a method claim. It covers specified acne-treatment use of azelaic acid under the limitations inherited from claim 1, not every manufacture or sale of azelaic acid.

Is 1,9-nonanedicarboxylic acid different from azelaic acid?

Generally no. Azelaic acid is commonly identified chemically as nonanedioic acid or 1,9-nonanedicarboxylic acid. The separate references in the claim appear to identify the same C9 dicarboxylic acid by different nomenclature.

Could the patent have covered azelaic acid cream formulations?

Yes, if the cream was used in the claimed acne-treatment method and satisfied the method limitations. The patent did not, however, claim a particular cream composition as a standalone product.

Are biosimilar rules relevant to this patent?

No. Azelaic acid is a small-molecule chemical active ingredient, not a biologic. The relevant regulatory pathway is generally the abbreviated new drug application pathway, not the biosimilar pathway under the Public Health Service Act.

References

U.S. Patent No. 4,386,104. (1983, May 31). Treatment of acne with dicarboxylic acids. United States Patent and Trademark Office.
United States Code, 35 U.S.C. § 154. Patent term.
United States Code, 35 U.S.C. § 271. Infringement of patent.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book.
Code of Federal Regulations, 21 C.F.R. § 314.53. Submission of patent information.
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, §§ 2701-2702. Patent term and expiration.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	22617 A/77	Apr 19, 1977
Italy	31471 A/77	Dec 30, 1977

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	3502778	⤷ Start Trial
Australia	524602	⤷ Start Trial
Belgium	866151	⤷ Start Trial
Canada	1137873	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,386,104

Summary for Patent: 4,386,104