United States Patent 4,447,424: Scope, Claims, Expiration, and Antiprogestin Patent Landscape

U.S. Patent No. 4,447,424 covers broad antiprogestomimetic steroid compositions and methods, including mifepristone, commonly known as RU-486. The patent issued on May 8, 1984, and its 17-year term expired on May 8, 2001. It therefore has no current blocking effect in the United States. Its historical importance is substantial because the claims reached the core chemical structure, pharmaceutical compositions, menstrual-induction methods, and pregnancy-interruption uses associated with mifepristone.

What does U.S. Patent 4,447,424 cover?

The patent covers 19-nor steroids and 19-nor-D-homo-steroids with antiprogestational activity. The claims define the compounds through a Markush formula rather than through a single chemical entity.

The central structural requirements are:

Claim feature	Scope
Steroid nucleus	19-nor steroid or 19-nor-D-homo-steroid
C-11 substituent, R1	Organic radical containing nitrogen, phosphorus, or silicon; the atom directly attached to the steroid C-11 position must be carbon
C-17 substituent, R2	Hydrocarbon containing one to eight carbon atoms
Ring X	Five- or six-membered ring, optionally substituted and optionally containing a double bond
B and C positions	Either a double bond or an epoxy group
Position 3	Ketone, ketal, oxime, oxime ether, or methylene functionality
Pharmaceutical form	Active compound with an inert carrier, or a non-toxic pharmaceutically acceptable acid-addition salt
Medical use	Induction of menses, luteal-phase treatment, and interruption of pregnancy

The claims are directed to both product compositions and therapeutic methods. Claims 1 through 14 cover compositions. Claims 15 through 36 cover methods of administration.

The patent's broadest practical genus is centered on steroids carrying an aryl or heteroatom-containing group at C-11 and a hydrocarbon substituent at C-17. The specification and dependent claims narrow that genus toward the substituted phenyl structures associated with mifepristone and related antiprogestins.

Which claims are independent in U.S. Patent 4,447,424?

Claims 1 and 15 are the two principal independent claims.

Claim 1: antiprogestomimetic composition

Claim 1 requires:

An antiprogestomimetically effective amount of at least one qualifying steroid;
A compound falling within the defined Markush formula;
A pharmaceutical carrier; and
Coverage for pharmaceutically acceptable acid-addition salts.

The claim is composition-based. Infringement would historically have required making, using, selling, offering to sell, or importing a composition containing a compound within the claimed genus and an inert carrier.

Claim 1 does not require mifepristone specifically. It potentially reaches numerous analogues if they satisfy every structural limitation.

Claim 15: method of inducing menses

Claim 15 covers administering a qualifying compound to warm-blooded animals when progesterone has a physiologically essential role. The method is framed as inducing menses, with the same broad steroid genus used in claim 1.

Claims 16 through 21 narrow the method by specifying:

Administration to women;
Treatment during the luteal phase;
Administration at the end of the luteal phase;
Oral or local administration;
Treatment for one to five days.

Claim 18 separately recites pregnancy interruption. That claim is commercially and regulatory significant because it tracks the principal medical use later associated with mifepristone.

How do the dependent claims narrow the patent scope?

The dependent claims move from a broad chemical genus toward specific structural classes and named compounds.

Claims	Principal limitation
2 and 22	B and C form a double bond
3 and 23	R2 is methyl
4, 24	Specific D-ring and substituent architecture
5 and 25	Saturated D ring, hydrogen R5/R6, and n=1
6 and 26	Position-3 group is a ketone
7 and 27	R1 contains nitrogen
8 and 28	Nitrogen-containing alkyl or heteroatom-substituted radical
9 and 29	Nitrogen-containing heterocycle
10 and 30	Aryl or aralkyl groups with amino-containing substituents
11 and 31	Specific pyridyl and related groups
12 and 32	Oxidized nitrogen
13 and 33	Listed active compounds and salts
14 and 35	A specific mifepristone-type compound
16, 20, 34, 36	Luteal-phase use and specifically listed compounds

Claims 14, 35, and 36 are the claims most directly associated with mifepristone. The compound recited in those claims is:

11β-[4-(N,N-dimethylamino)phenyl]-17α-(prop-1-ynyl)-Δ4,9-estradiene-17β-ol-3-one.

That is the chemical structure generally identified as mifepristone, although nomenclature and stereochemical formatting differ across patent, regulatory, and scientific records.

Does U.S. Patent 4,447,424 cover mifepristone?

Yes. The patent expressly identifies the mifepristone structure in composition and method claims. Claims 14 and 35 recite the compound itself in a pharmaceutical composition or therapeutic method. Claims 13, 33, 34, and 36 include mifepristone in lists of specific antiprogestational compounds and related analogues.

The claim set also covers:

The free-base steroid;
Certain acid-addition salts;
Pharmaceutical compositions containing the active compound;
Oral and local administration;
Luteal-phase administration;
Administration for one to five days;
Pregnancy interruption.

The patent therefore combined chemical, formulation, and method-of-use coverage. It was not limited to a manufacturing process.

What is the legal status and expiration date of Patent 4,447,424?

U.S. Patent 4,447,424 issued May 8, 1984, to Roussel-Uclaf. Because the application was filed before the June 8, 1995 change from a 17-year-from-grant term to a 20-year-from-earliest-effective-filing term, the applicable term was generally 17 years from issuance. The patent expired May 8, 2001, absent an unusual term adjustment or effective terminal disclaimer. The patent record does not create a current enforceable exclusionary right. [1]

Event	Date
Priority period	1980
U.S. application period	1981
Patent issued	May 8, 1984
Patent term basis	17 years from issuance
Expected expiration	May 8, 2001
Current status	Expired

The expired patent can remain relevant as prior art, a prosecution-history reference, a freedom-to-operate benchmark, and evidence of historical ownership. It cannot independently block a current generic or branded product.

What was the historical patent landscape for mifepristone?

Mifepristone's historical protection involved several layers:

Core compound patents covering the steroid structure;
Related patents covering analogues and salts;
Method-of-use patents directed to pregnancy interruption and reproductive applications;
Regulatory exclusivity associated with FDA approval;
Commercial rights and distribution arrangements.

Roussel-Uclaf developed the compound and held the principal early intellectual-property position. In the United States, the Population Council obtained rights connected with development and commercialization. Danco Laboratories later became the commercial sponsor associated with Mifeprex in the U.S. market. The commercial arrangements were central because Roussel-Uclaf did not initially pursue broad direct U.S. commercialization of mifepristone. [2][3]

The older patent portfolio did not remain the main U.S. barrier after 2001. By the time mifepristone reached FDA approval, regulatory controls, restricted distribution, manufacturing capacity, and political and operational constraints were more important than the expired compound patent.

What was the FDA status of mifepristone?

The FDA approved Mifeprex, containing mifepristone, in September 2000 for use with misoprostol for medical termination of intrauterine pregnancy through seven weeks of gestation under the original approval. FDA later expanded the approved gestational age to 10 weeks and modified dispensing requirements. [4]

In January 2023, FDA approved changes that permitted certified pharmacies to dispense mifepristone, subject to the applicable Risk Evaluation and Mitigation Strategy. In January 2024, FDA removed the in-person dispensing requirement while retaining elements of the REMS framework. [5]

Mifeprex is listed under NDA 020687. Korlym, a separate mifepristone product marketed by Corcept Therapeutics, was approved under NDA 202107 in 2012 for hyperglycemia secondary to endogenous Cushing's syndrome in adults who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have failed surgery. [6]

These approvals are distinct from the expired patent. FDA approval does not restore patent exclusivity.

What is the Orange Book status of mifepristone?

The Orange Book is relevant to approved drug products and listed patents, not to every historical compound patent. Patent 4,447,424 expired decades ago and is not a current Orange Book barrier to generic entry.

Mifeprex and Korlym have separate FDA approval histories, sponsors, labeling, and commercial indications. A current Orange Book analysis must distinguish:

Product	Sponsor	FDA indication	Patent relevance
Mifeprex	Danco Laboratories	Medical termination of intrauterine pregnancy with misoprostol	Historical compound patent expired
Korlym	Corcept Therapeutics	Hyperglycemia associated with endogenous Cushing's syndrome	Separate product and potential later patent estate

The existence of later patents or regulatory exclusivity for a particular product does not revive U.S. Patent 4,447,424. Any current patent challenge must be evaluated against the patents listed for the specific reference product and indication.

Were there Paragraph IV challenges to Patent 4,447,424?

No live Paragraph IV challenge can target Patent 4,447,424 because the patent expired in 2001. A Paragraph IV certification concerns a listed patent alleged to be invalid, unenforceable, or not infringed. An expired patent cannot delay approval through the Hatch-Waxman 30-month stay.

Historically, a generic applicant could have challenged the patent while it was in force if the patent had been listed and relevant to the reference product. That opportunity is no longer commercially meaningful. Current generic litigation involving mifepristone would instead concern later patents, formulation or manufacturing patents, labeling issues, regulatory requirements, or product-specific exclusivity.

What formulation patents protect mifepristone?

Patent 4,447,424 does not claim a narrow modern formulation such as a particular tablet composition, coating, dissolution profile, packaging configuration, or fixed-dose combination. Its formulation language is functional and broad: the active compound is combined with an inert carrier.

The patent therefore provides only limited formulation specificity. It could historically reach a conventional pharmaceutical composition containing a covered compound, but it does not define a sophisticated formulation platform.

Later patent strategies for mifepristone products may focus on:

Tablet composition and excipient selection;
Improved stability;
Dose uniformity;
Blister or unit-dose packaging;
Combination products with misoprostol;
Modified dosing regimens;
Treatment of non-reproductive endocrine disorders;
Manufacturing controls and impurity profiles.

Those later rights must be analyzed separately from Patent 4,447,424.

What manufacturing and intellectual-property barriers remain?

The expired patent eliminates the principal historical composition patent barrier, but commercial entry can still face non-patent obstacles:

FDA abbreviated or full-application requirements;
Demonstration of pharmaceutical equivalence and bioequivalence;
Controlled-substance and distribution compliance, where applicable;
REMS certification and dispensing obligations;
Qualified manufacturing capacity;
Supply of high-quality steroid intermediates;
Control of stereochemistry and impurity specifications;
Product liability exposure;
Access to abortion and reproductive-health distribution channels;
Separate approval strategy for endocrine indications.

Mifepristone is a small molecule, so biosimilar risk is not applicable. The relevant competitive pathway is generic-drug approval, not the 351(k) biosimilar pathway.

How strong was the patent estate compared with competing antiprogestins?

Patent 4,447,424 was chemically broad and commercially important, but its present strength is zero because it is expired. Historically, it had several strengths:

Broad Markush coverage;
Express inclusion of mifepristone;
Composition and method claims;
Pregnancy-interruption coverage;
Claims directed to salts and pharmaceutical carriers;
Multiple dependent claims narrowing to nitrogen-containing aryl substituents.

Its weaknesses included:

Expiration before the modern commercial expansion of mifepristone;
Lack of detailed protection for modern formulation technologies;
Limited process coverage in the asserted claims;
Potential validity issues associated with broad genus claims and written-description support;
Dependence on regulatory and commercial rights outside the patent itself.

Competing antiprogestins, including ulipristal acetate, onapristone, telapristone, asoprisnil, and vilaprisan, were protected through separate chemical and use patent families. They should not be treated as substitutes for mifepristone patent rights. Their development status, indications, and patent terms differ materially.

What generic launch scenarios exist today?

For the expired patent alone, generic launch risk is unrestricted by Patent 4,447,424. The relevant scenarios are:

Scenario	Patent effect of 4,447,424	Principal remaining issue
Generic mifepristone for pregnancy termination	None	FDA approval, REMS, product and labeling requirements
Generic mifepristone for Cushing's syndrome	None	Korlym-specific regulatory and later-patent analysis
New antiprogestin analogue	No direct blocking right	Freedom to operate against later chemical patents
New formulation	No direct blocking right	Formulation, combination, and packaging patents
Importation of active pharmaceutical ingredient	No patent barrier from 4,447,424	Manufacturing, quality, and regulatory compliance

A generic applicant cannot be delayed by a patent that expired in 2001. The principal business risks are regulatory execution, supply reliability, clinical labeling, and any later patent rights associated with the chosen product and indication.

What geographic coverage did the patent have?

U.S. Patent 4,447,424 had territorial effect only in the United States. Corresponding foreign patent applications and grants may have protected related compounds in Europe and other jurisdictions, but U.S. expiration did not automatically determine foreign status.

For a global freedom-to-operate analysis, each jurisdiction requires separate review of:

National patent-family members;
Local term adjustments;
Supplementary protection certificates;
Patent-term extensions;
Opposition and revocation proceedings;
Local regulatory exclusivity;
Product-specific formulation and process patents.

The U.S. patent's 2001 expiration date cannot be used as a worldwide expiration date.

Key Takeaways

U.S. Patent 4,447,424 covers a broad genus of antiprogestational 19-nor steroids and expressly includes mifepristone.
Claims 1 through 14 cover compositions; claims 15 through 36 cover methods, including menses induction and pregnancy interruption.
Claims 14, 35, and 36 are the principal mifepristone-specific claims.
The patent issued May 8, 1984, and expired May 8, 2001.
The patent has no current blocking or Paragraph IV significance.
It does not provide detailed modern protection for tablet formulation, packaging, manufacturing processes, or combination products.
Mifepristone is a small molecule, so biosimilar analysis is irrelevant; generic-drug law is the applicable pathway.
Current commercial risk must be assessed against later product-specific patents, FDA requirements, REMS obligations, manufacturing capacity, and indication-specific rights.
The historic patent estate was broader than a single-compound patent because it included analogues, salts, compositions, and methods.
The patent's commercial impact ended with expiration, while regulatory and distribution constraints continued to affect market access.

FAQs

Does Patent 4,447,424 still prevent manufacture of mifepristone?

No. The patent expired May 8, 2001, and cannot currently block manufacture, sale, or importation based on its claims.

Is mifepristone protected by a biologic patent?

No. Mifepristone is a chemically synthesized small molecule. Generic-drug approval, not biosimilar approval, is the relevant pathway.

Did Patent 4,447,424 claim misoprostol?

No. The patent claims antiprogestational steroids, including mifepristone and related compounds. It does not claim misoprostol as an active ingredient.

Did the patent cover treatment of Cushing's syndrome?

The disclosed compound may be used for antiprogestational activity, but the supplied claims focus on menses induction, luteal-phase treatment, and pregnancy interruption. Korlym's Cushing's syndrome indication was approved much later under a separate FDA application and requires separate patent analysis.

Can a foreign patent extend the U.S. term of Patent 4,447,424?

No. Foreign patent rights do not extend the term of a U.S. patent. Any foreign protection had to be evaluated under the law and term rules of the relevant country.

References

United States Patent and Trademark Office. (1984). U.S. Patent No. 4,447,424, Steroids with antiprogestational activity. U.S. Department of Commerce.
United States Patent and Trademark Office. (1983). U.S. Patent No. 4,386,085, Steroids with antiprogestational activity. U.S. Department of Commerce.
Population Council. (2000). Mifeprex approval and commercial rights materials. Population Council.
U.S. Food and Drug Administration. (2000). Mifeprex approval letter and prescribing information. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Mifeprex prescribing information and Risk Evaluation and Mitigation Strategy materials. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2012). Korlym approval letter and prescribing information. U.S. Department of Health and Human Services.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	81 00272	Jan 09, 1981

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0057115	⤷ Start Trial	SPC/GB93/030	United Kingdom	⤷ Start Trial
Austria	12239	⤷ Start Trial
Austria	23167	⤷ Start Trial
Austria	23344	⤷ Start Trial
Austria	396787	⤷ Start Trial
Austria	46702	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,447,424

Summary for Patent: 4,447,424