Details for Patent: 3,959,322

Summary for Patent: 3,959,322

Title:	Synthesis of 13-alkyl-gon-4-ones
Abstract:	The preparation of 13-methylgon-4-enes and novel 13-polycarbonalkylgon-4-enes by a new total synthesis is described. 13-Alkylgon-4-enes having progestational, anabolic and androgenic activities are prepared by forming a tetracylic gonane structure unsaturated in the 1,3,5(10),9(11) and 14-positions, selectively reducing in the B- and C-rings, and converting the aromatic A-ring compounds so-produced to gon-4-enes by Birch reduction and hydrolysis.
Inventor(s):	Gordon Alan Hughes, Herchel Smith
Assignee:	Individual
Application Number:	US04/388,820
Patent Claim Types: see list of patent claims	Use; Compound;

United States Drug Patent 3,959,322: Scope, Claims, Expiration and Patent Landscape

US Patent 3,959,322 is a foundational steroid composition and process patent covering 13-alkyl-substituted gon-4-en steroid compounds, including the chemical structure of levonorgestrel. It issued in 1976 and expired in 1993 under the pre-URAA 17-year term measured from grant. The patent has no current blocking effect in the United States. Its historical significance is strongest for levonorgestrel, norgestrel-related compounds, steroid intermediates, and early manufacturing routes.

What does US Patent 3,959,322 cover?

US 3,959,322 claims steroid compounds with a gon-4-ene nucleus bearing a polycarbon alkyl substituent at the 13-position. The broadest composition claim is claim 1:

• A gon-4-ene steroid nucleus;
• A 13-position polycarbon alkyl radical containing about 2 to 16 carbon atoms;
• A total carbon-carbon skeleton containing at least 19 and no more than 40 carbon atoms.

The patent also claims:

1. Specific 17-alkyl, 17-alkynyl and haloalkynyl steroids;
2. 17-hydroxy compounds and their esters;
3. Specific acetates, decanoates and tetrahydropyranyl ethers;
4. 13β-ethyl and 13β-n-propyl analogues;
5. Process routes using Grignard reagents, alkali-metal acetylides, mineral-acid hydrolysis and Birch reduction;
6. Broad formula-defined steroid genera;
7. Compounds with 3-oxo, 3-hydroxy or hydrolysable 3-position substituents.

The patent is directed to composition-of-matter protection rather than a therapeutic indication. It does not depend on contraceptive use, emergency contraception, hormone replacement, or a particular dosage form.

What drug compounds fall within the claims?

The most commercially important structure expressly recited in the claims is levonorgestrel.

Levonorgestrel

Levonorgestrel is chemically identified as 13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one. That structure is expressly recited in claim 5 and is also captured by several later dependent claims, including claims 32, 33, 35, 36, 40, 42 and 43.

The claim mapping is:

Patent limitation	Levonorgestrel
Gon-4-ene nucleus	Present
13-position polycarbon alkyl group	13β-ethyl
17α substituent	Ethynyl
17β functionality	Hydroxy
3-position functionality	3-one
Carbon skeleton	C21 steroid
Claimed species	Expressly recited in claim 5

Because claim 5 names the compound directly, infringement analysis would not depend on proving that levonorgestrel falls within a broad genus. The claim is a species claim.

Norgestrel-related compounds

The patent also covers compounds related to norgestrel and other 13β-ethyl steroid contraceptives. Norgestrel is the racemic mixture corresponding to the active levonorgestrel stereoisomer and its enantiomer. The supplied claims do not use modern regulatory naming conventions, so the scope must be determined from stereochemistry and structural limitations rather than drug names.

Claim 3 covers a 13β,17α-diethyl compound. Claims 4 through 6 cover 17-alkynyl and 17-chloroethynyl derivatives. Claims 24 through 27 expand the claimed examples to n-propyl and methyl-substituted steroid analogues.

Other covered steroid classes

The claim set also reaches:

• 17-lower alkanoates;
• 17-acetates;
• 17-decanoates;
• Tetrahydropyranyl ethers;
• 3,17-diols;
• 3-acetoxy derivatives;
• Lactone derivatives;
• Haloethynyl steroids;
• 13β-ethyl and 13β-n-propyl analogues;
• Steroids with up to 40 carbon atoms in the carbon-carbon skeleton.

The patent therefore has a broad medicinal-chemistry platform character. The commercially relevant portion is narrower than the literal claim set because many claimed analogues were research compounds rather than marketed drugs.

How broad is claim 1 of US 3,959,322?

Claim 1 is the principal genus claim. Its breadth derives from the combination of a broad steroid nucleus, a broad 13-position substituent and a wide carbon-count range.

Structural limitations

The claim requires a gon-4-ene nucleus. In steroid nomenclature, this generally indicates:

• A gonane steroid framework;
• A double bond at the 4-position;
• A steroid carbon skeleton modified at the 13-position.

The 13-substituent must be a polycarbon alkyl radical containing 2 to approximately 16 carbon atoms. The wording appears to reflect historical patent terminology. It is broader than an ethyl group and can encompass larger alkyl or substituted hydrocarbon chains, subject to the carbon-skeleton ceiling.

The claim does not, on its face, require:

• A 3-keto group;
• A 17-hydroxy group;
• A 17α-ethynyl group;
• A particular ester;
• A pharmaceutical formulation;
• A contraceptive use.

That makes claim 1 materially broader than the levonorgestrel-specific claims.

Carbon-skeleton limitation

The total carbon-carbon skeleton must contain at least 19 and no more than 40 carbon atoms. This limitation excludes smaller steroid fragments and compounds exceeding the stated upper limit. It also helps define the intended chemical class without specifying every substituent.

For levonorgestrel, the carbon skeleton is C21, which falls within the claimed range.

Stereochemical limitations

The claim language supplied for claim 1 does not expressly identify β or α stereochemistry at every position. Later claims narrow the scope by specifying configurations such as 13β-ethyl and 17α-ethynyl. In a litigation setting, the claim would be interpreted with the patent specification, structural drawings, nomenclature conventions and prosecution history.

Claims 5 and 25 are more commercially significant than claim 1 because they identify the 13β-ethyl stereochemistry and specific 17-position substituents.

Which claims cover levonorgestrel and its derivatives?

Claim	Subject matter	Relevance to levonorgestrel
1	Broad 13-polycarbon alkyl gon-4-ene genus	Genus coverage
4	13-polycarbon alkyl, 17-alkynyl, 17β-hydroxy, 3-one compounds	Genus coverage
5	13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one	Direct levonorgestrel species claim
17	Levonorgestrel tetrahydropyranyl ether	Protected intermediate or derivative
19	Levonorgestrel acetate	Ester derivative
22	13β-ethyl-17α-ethynyl gon-4-en-3,17β-diol acetate	Related protected derivative
32	Levonorgestrel or its 17-lower alkanoate	Compound and ester genus
33	Levonorgestrel or its 17-acetate	Levonorgestrel acetate coverage
35	13β-ethyl 17-alkynyl compound or lower alkanoate	Broader ethynyl genus
36	Same compound or acetate	Ester coverage
40	13β-ethyl 17-ethynyl steroid or acetate	Broad steroid formulation
42	Ethynyl steroid with 3-oxo, hydroxy or hydrolysable group	Broad functional genus
43	Same class with acetate	Ester-specific genus

Claims 32 through 43 appear to have been added or amended to reinforce coverage of ethynyl compounds and their lower alkanoates. Their practical scope depends on the issued patent text and prosecution record, not solely on the claim transcription supplied.

What manufacturing processes does US 3,959,322 claim?

Claims 9 through 11 are process claims. They protect particular synthetic sequences rather than every method of making the covered steroids.

Grignard route

Claim 9 requires:

1. A gona-2,5(10)-diene-17-one intermediate bearing a 13-position polycarbon alkyl group;
2. Treatment with an alkyl Grignard reagent;
3. Formation of a 17β-alkyl, 17α-ol intermediate;
4. Mineral-acid hydrolysis.

A manufacturer using a materially different route may avoid literal infringement of claim 9, even if the final product is the same. The product claims, however, would historically have created independent infringement risk.

Acetylide route

Claim 10 requires treatment of the 17-ketone intermediate with an alkali-metal acetylide followed by mineral-acid hydrolysis. This is directed to the introduction of an ethynyl or related alkynyl group at the 17-position.

Annulation and Birch-reduction route

Claim 11 claims a multistep process involving:

• A 5-phenylpent-1-yne starting material;
• Mannich reaction;
• Hydration to a 3-keto compound;
• Michael condensation with a substituted dioxocyclopentane;
• Acid-promoted cyclodehydration;
• Selective hydrogenation;
• Birch reduction;
• Mineral-acid hydrolysis.

The supplied text omits step "(g)" and contains typographical errors. The issued patent should control for any historical claim-construction analysis.

What are the principal weaknesses in the claim set?

The patent was issued and therefore carried the statutory presumption of validity during its enforceable term. Its current commercial weakness is expiration, not claim invalidity. Historically, potential pressure points would have included the following.

Ambiguous historical terminology

"P olycarbon-alkyl" and related expressions are not standard modern regulatory nomenclature. The specification would be needed to determine whether the term means a hydrocarbon alkyl radical, a substituted alkyl radical, or a broader carbon-containing substituent.

Formula claims are unavailable in the supplied text

Claims 12 through 14, 28 and 44 rely on structural drawings identified as SPC1 through SPC5. The formulas are missing from the text provided. Their exact scope cannot be established from the transcription alone.

Dependent-claim drafting

Several claims use "claim 1" as the dependency even where the subject matter appears to restate or further narrow claims 4, 29 or 30. This may reflect historical prosecution amendments or transcription errors. Dependency must be confirmed against the official issued patent.

Product-versus-process distinction

A process-around strategy could avoid claims 9 through 11 by changing starting materials, reagents or sequencing. That strategy would not avoid a composition claim covering the final molecule.

Prior-art exposure

The claimed chemistry is closely related to established steroid synthesis and to known 17α-ethynyl steroid chemistry. Potential prior-art issues would have focused on:

• Known gon-4-en-3-one steroids;
• 13-alkyl steroid analogues;
• 17α-ethynyl steroid contraceptives;
• Conventional Grignard and acetylide additions;
• Steroid annulation and Birch reduction.

These issues mattered during prosecution and potential validity challenges. They do not restore rights after expiration.

When did US Patent 3,959,322 expire?

US 3,959,322 issued in 1976. As a pre-June 8, 1995 U.S. patent, its ordinary term was 17 years from issue under the law then in effect. On that basis, the patent expired in 1993.

Event	Date or period
U.S. patent application	Before 1976
Patent grant	1976
Statutory term	17 years from grant
Estimated ordinary expiration	1993
Current status	Expired
Patent-term adjustment	Not applicable under the modern PTA regime
Current blocking right	None in the United States

The exact expiration date should be taken from the USPTO patent record if a historical damages calculation is required. The 1993 expiration conclusion is not affected by later FDA exclusivity rules.

What is the Orange Book status of levonorgestrel under this patent?

US 3,959,322 is not a current Orange Book patent for levonorgestrel products. The patent expired decades before the modern product-specific Orange Book listing system became commercially important.

Levonorgestrel products have included:

• Emergency contraceptive tablets;
• Oral contraceptive combinations;
• Intrauterine delivery systems;
• Extended-release intrauterine systems;
• Combination hormonal products.

Patent protection for those products, where present, generally concerns the device, formulation, release profile, delivery system, manufacturing method or a particular combination. It does not revive the expired composition claims in US 3,959,322.

The FDA Orange Book lists patents and exclusivity associated with approved drug products, but an expired foundational compound patent is not a current barrier to abbreviated new drug application approval.[2]

Are there current Paragraph IV challenges or generic-entry risks?

There is no current Paragraph IV risk associated with US 3,959,322 itself because the patent expired in 1993. A generic manufacturer would not need to certify that this patent remains enforceable.

Levonorgestrel tablets

Generic-entry risk for levonorgestrel tablets is high from a patent perspective because the active compound is off-patent and widely manufactured. Regulatory barriers center on bioequivalence, labeling, quality systems and product-specific patents, not the expired compound patent.

Levonorgestrel intrauterine systems

The risk profile differs for intrauterine systems. A manufacturer may need to address patents covering:

• Device geometry;
• Hormone reservoir architecture;
• Polymer membranes;
• Release rates;
• Insertion systems;
• Manufacturing methods;
• Use in contraception or heavy menstrual bleeding.

Those rights are product-specific and separate from US 3,959,322.

Norgestrel and Opill

Norgestrel, marketed in the United States as Opill, received FDA approval as a progestin-only oral contraceptive. The active pharmaceutical ingredient is an old steroid and is not protected by US 3,959,322 today. Regulatory exclusivity, labeling requirements and any later product patents must be analyzed separately from the 1976 composition patent.[3]

Does biosimilar risk apply to this patent?

No. Levonorgestrel and norgestrel are small-molecule chemical drugs, not biologics. The biosimilar pathway under the Public Health Service Act does not apply.

Competitive products proceed through generic-drug pathways, including ANDAs, or through full or hybrid applications where the dosage form or delivery system is materially different.

What licensing and litigation history matters?

The patent reflects the historical steroid research and development programs of the pre-generic pharmaceutical industry. Schering-related entities were major participants in steroid chemistry and hormonal contraceptives. Commercial rights in individual levonorgestrel products later moved through product-specific licensing, acquisitions, distribution arrangements and regional commercialization agreements.

Those later arrangements do not extend the term of US 3,959,322.

No current U.S. infringement litigation, settlement agreement or Paragraph IV dispute can preserve this patent's exclusionary effect after expiration. Historical disputes involving levonorgestrel products may have concerned later device, formulation or method-of-use patents rather than the expired compound patent.

How strong is the historical patent estate?

Dimension	Assessment
Composition coverage	Historically strong for expressly claimed compounds, including levonorgestrel
Genus breadth	Broad, but dependent on construction of "polycarbon alkyl" and the specification
Process coverage	Moderate; limited to specified synthetic routes
Formulation coverage	Weak as a standalone modern product patent; mainly ester and derivative chemistry
Method-of-use coverage	Minimal; claims are not directed to contraceptive treatment
Geographic coverage	U.S. only for this patent; foreign protection would require separate family patents
Current enforceability	None; expired
Biosimilar relevance	None
Generic relevance	Foundational historical patent only
Commercial importance today	Low as an exclusionary right; high as historical prior art

The patent's strongest historical feature was the combination of broad genus claims and direct species claims. Claim 5 provided a clean composition claim to levonorgestrel, while claims 32 through 43 attempted to extend coverage to esters, lower alkanoates and related functional variants.

Its principal limitation was the absence of meaningful therapeutic-use or delivery-system coverage. Later commercial products could be protected, if at all, through separate patents directed to dosage forms, intrauterine devices, release systems and indications.

What is the competitive patent landscape for levonorgestrel?

The current landscape is divided into four categories.

Generic oral products

Levonorgestrel tablets are exposed to generic competition. The expired compound patent creates no current entry barrier. Manufacturing know-how, regulatory compliance and supply economics are more important than foundational composition rights.

Emergency contraception

Products such as Plan B and generic levonorgestrel emergency contraceptives compete primarily on FDA approval, retail distribution, branding and pricing. The active ingredient is long off-patent.

Intrauterine systems

Levonorgestrel-releasing intrauterine systems have a more complex patent profile. The commercial moat historically depended on device engineering, polymer and reservoir design, controlled release and insertion technology. These rights are distinct from US 3,959,322 and may expire on different schedules.

Combination oral contraceptives

Combination products may involve patents or exclusivity associated with the estrogen component, formulation, dosing schedule, regimen or method of use. The levonorgestrel component itself is not protected by the 1976 patent.

What geographic coverage does US 3,959,322 provide?

The patent provides only U.S. rights. It does not establish protection in Europe, Japan, Canada, Australia or other jurisdictions.

A complete international landscape would require review of:

• Priority applications;
• PCT filings;
• National-phase applications;
• Foreign grants;
• Local patent-term rules;
• Supplementary protection certificates;
• Patent-term extensions;
• Local assignments and licenses.

Any corresponding foreign rights would also be historical and would generally have expired by now, given the age of the U.S. grant.

Key Takeaways

• US 3,959,322 covers 13-alkyl-substituted gon-4-en steroid compounds and manufacturing processes.
• Claim 5 expressly covers levonorgestrel.
• Claims 32 through 43 extend coverage to levonorgestrel esters, lower alkanoates and related ethynyl steroid structures.
• Claims 9 through 11 protect specified synthetic routes, not every process for making the compounds.
• The patent issued in 1976 and expired under the pre-URAA 17-year term in 1993.
• It has no current U.S. blocking effect, Orange Book relevance or Paragraph IV significance.
• Levonorgestrel is a small molecule, so biosimilar analysis does not apply.
• Current commercial protection for levonorgestrel products, especially intrauterine systems, must be analyzed through later formulation, device, delivery and method-of-use patents.
• The patent remains relevant as historical prior art and as an origin point for the levonorgestrel patent estate.

FAQs

Is levonorgestrel specifically named in US Patent 3,959,322?

No modern drug name is required. The chemical structure corresponding to levonorgestrel is expressly recited in claim 5 as 13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one.

Can a company obtain a new patent on levonorgestrel itself?

A new patent cannot ordinarily reclaim the expired compound as such. Patent protection may still be available for a genuinely novel formulation, delivery system, device, manufacturing process, combination or therapeutic use that satisfies current patentability standards.

Does the patent cover levonorgestrel intrauterine devices?

It covers the active steroid compound and certain chemical derivatives, not the complete intrauterine device platform. Device and controlled-release patents must be analyzed separately.

Did FDA approval extend the term of US 3,959,322?

No. FDA approval does not extend an expired pre-1995 patent. Patent-term restoration and modern patent-term adjustment rules do not revive this patent's 1993 expiration.

Is norgestrel protected by the same patent today?

No. Any historical coverage would have ended when the patent expired. Current regulatory or commercial rights for norgestrel products arise from later product-specific patents, exclusivity or regulatory approvals, if any.

References

1. United States Patent and Trademark Office. (1976). U.S. Patent No. 3,959,322, 13-alkyl-17-hydroxy-gon-4-en-3-ones. https://patents.google.com/patent/US3959322
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
3. U.S. Food and Drug Administration. (2023). FDA approves first nonprescription daily oral contraceptive. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive
4. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
5. United States Code, 35 U.S.C. §§ 154, 156. (2024). Term of patent; patent term extension. https://uscode.house.gov/lastrls/2024title35.htm

Drugs Protected by US Patent 3,959,322

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 3,959,322

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	256353
Austria	264728
Austria	264731
Austria	268544
Austria	281313
Austria	282083
Belgium	645390