Details for Patent: 5,604,213

Summary for Patent: 5,604,213

Title:	17-substituted steroids useful in cancer treatment
Abstract:	Compounds of the general formula (1) (I) wherein X represents the residue of the A, B and C rings of a steroid, R represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms, R14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, or a hydroxy or alkylcarbonyloxy group of 2 to 5 carbon atoms or R14 and R15 together represent a double bond, and R16 represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or phannaceutically acceptable acid addition salts, are useful for treatment of androgen-dependent disorders, especially prostatic cancer, and also oestrogen-dependent disorders such as breast cancer.
Inventor(s):	Susan E. Barrie, Michael Jarman, Gerard A. Potter, Ian R. Hardcastle
Assignee:	BTG International Ltd
Application Number:	US08/315,882
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 5,604,213: Scope, Claims, Expiration, and Abiraterone Patent Landscape

U.S. Patent No. 5,604,213 covers a broad genus of 17-substituted steroid compounds bearing a pyridyl-containing side chain, therapeutic use against androgen- or estrogen-dependent disorders, pharmaceutical compositions, and specific steroid derivatives. Its most commercially important compound is abiraterone, and its prodrug is abiraterone acetate, the active ingredient in Zytiga.

The patent is no longer the principal barrier to generic abiraterone acetate. The original compound patent expired after regulatory patent-term adjustment or extension, and later formulation patents became the relevant source of generic-entry risk. Abiraterone acetate is now subject to substantial generic competition in the United States.

What does U.S. Patent 5,604,213 cover?

The patent covers steroid compounds substituted at the 17-position with a pyridyl group, together with related salts, esters, compositions, and therapeutic uses.

The core commercial structure is:

• Abiraterone: 17-(3-pyridyl)androsta-5,16-dien-3β-ol.
• Abiraterone acetate: 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene.

Abiraterone acetate is expressly recited in claim 8. Abiraterone itself falls within the compounds listed in claim 4 and the broader genus of claim 1.

The patent’s claim architecture is as follows:

Claim group	Subject matter	Commercial relevance
Claim 1	Broad genus of steroid compounds with a pyridyl-substituted 17-position	Covers abiraterone and numerous analogues
Claim 2	Treatment of androgen-dependent or estrogen-dependent disorders	Covers therapeutic use
Claim 3	Compounds saturated and unsubstituted at the 11- and 12-positions	Narrows claim 1
Claim 4	Named 17-(3-pyridyl) steroid compounds, including abiraterone	Direct compound coverage
Claim 5	Compounds in which R is hydrogen	Narrows the side-chain definition
Claim 6	Additional named steroid analogues	Species claims
Claims 7-8	3β-alkanoyloxy derivatives and abiraterone acetate	Direct prodrug coverage
Claims 9-15	Pharmaceutical compositions	Formulation and carrier claims
Claims 16-21	Treatment of prostate cancer, breast cancer, and specified compounds	Method-of-use claims
Claim 22	Oral solid or sterile injectable compositions	Dosage-form claims

The patent was assigned to British Technology Group Limited, the organization associated with the underlying abiraterone research program. The patent issued on February 18, 1997, from a December 1991 U.S. filing based on an earlier priority filing.[1]

How broad is claim 1?

Claim 1 is a Markush genus claim. It attempts to cover a large family of steroid cores and permitted substitutions, provided the resulting molecule contains the specified pyridyl-substituted side-chain framework.

The claim reaches compounds based on steroid systems including:

• Androstane;
• Androstene;
• Androstadiene;
• Estratriene;
• Androstenediones;
• Fluorinated and oxygenated steroid derivatives;
• 19-nor steroid analogues.

It also permits multiple modifications to the steroid nucleus, including:

• 3-esters;
• Additional carbon-carbon double bonds;
• Oximes;
• 3-methylene derivatives;
• 3-carboxylates;
• 3-nitriles;
• 3-nitroso compounds;
• 3-desoxy compounds;
• Hydroxy, halo, alkyl, alkoxy, alkanoyloxy, benzoyloxy, oxo, methylene, and alkenyl substituents.

The claim excludes several specifically identified compounds. Those exclusions are important because they indicate that the applicants carved out known or potentially problematic prior-art species during prosecution. The exclusions include certain acetoxy, diacetoxy, methoxy, and pyridyl steroid compounds.

What does claim 1 mean for abiraterone?

Abiraterone is within the claim 1 genus because it has:

• A steroid nucleus;
• A 3β-hydroxyl group;
• A 5,16-diene structure;
• A 17-(3-pyridyl) substituent;
• The required hydrogen or alkyl side-chain parameters.

Abiraterone acetate is also within the genus because the 3β-hydroxyl group is esterified with acetate. Claim 8 confirms this species expressly.

The practical importance of claim 1 was greatest before expiration because it could capture close analogues that avoided the narrower named-compound claims. Its breadth also created potential validity issues based on written description, enablement, anticipation, and obviousness. For current generic-entry analysis, those issues have limited commercial impact because the patent term has ended.

Which claims specifically cover abiraterone and abiraterone acetate?

Abiraterone

Abiraterone is covered most directly by:

• Claim 1, as a member of the broad compound genus;
• Claim 4, which expressly lists 17-(3-pyridyl)androsta-5,16-dien-3β-ol;
• Claim 5, where R is hydrogen;
• Claims 9-15, when formulated as a pharmaceutical composition;
• Claims 16-21, when used for the specified therapeutic indications.

Abiraterone acetate

Abiraterone acetate is covered most directly by:

• Claim 1, because it is a 3-ester derivative;
• Claim 4, which includes the corresponding 3-esters;
• Claim 7, which covers 3β-alkanoyloxy derivatives with a two- to four-carbon alkanoyloxy group;
• Claim 8, which expressly identifies 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene;
• Claim 14, covering pharmaceutical compositions containing claim 7 compounds;
• Claim 15, covering compositions containing claim 8;
• Claims 20 and 21, covering therapeutic use of those compounds.

Claim 8 is the most important historical claim for Zytiga because it names the active pharmaceutical ingredient directly.

When did U.S. Patent 5,604,213 expire?

The patent issued under the pre-Uruguay Round Agreements Act patent-term regime, under which the ordinary term was generally 17 years from issuance. Its nominal term therefore ran from the February 18, 1997 issue date until February 18, 2014, subject to applicable regulatory patent-term extension or adjustment.[1]

The patent was listed in the FDA Orange Book for abiraterone acetate products. FDA listing information and subsequent generic approvals show that the patent’s effective regulatory protection extended beyond its nominal term, but it did not remain a current barrier to generic approval after the mid-2010s.[2]

The important business conclusion is:

Event	Timing
U.S. patent issued	February 18, 1997
Nominal pre-URAA term	Approximately 17 years from issuance
Regulatory extension or adjustment	Extended effective protection beyond nominal expiration
Generic abiraterone approvals	Began in 2018
Current status	Expired; no remaining exclusivity from this patent

The exact operative expiration date should be taken from the USPTO patent-term record and the applicable FDA Orange Book entry rather than from the issue date alone. The patent is not a live composition-of-matter right today.

What was the Orange Book status of patent 5,604,213?

Patent 5,604,213 was listed for abiraterone acetate products, including Zytiga. Its listing related to the active ingredient and associated product protection rather than merely a manufacturing process.

The patent’s Orange Book significance was based on three elements:

1. Direct coverage of abiraterone acetate.
2. Coverage of abiraterone-related compositions.
3. Method claims directed to androgen-dependent diseases, including prostate cancer.

The patent listing supported Paragraph IV certification activity by generic applicants. Once the patent term ended, the original patent ceased to block approval. Later Orange Book-listed formulation patents created separate certification and litigation issues.

Did the patent generate Paragraph IV litigation?

Generic applicants seeking approval for abiraterone acetate products were required to address listed patents through the ANDA certification process. Paragraph IV certifications assert that a listed patent is invalid, unenforceable, or not infringed.

The principal commercial disputes surrounding generic abiraterone involved:

• The original compound patent;
• Later formulation patents;
• Product-specific patents listed for 250 mg and 500 mg dosage forms;
• Janssen’s efforts to delay or control generic entry through secondary patent protection.

Because Patent 5,604,213 has expired, it cannot support a current injunction against an ANDA applicant. Any historical Paragraph IV dispute involving this patent is now relevant mainly to launch timing, damages history, settlement economics, and patent-estate analysis.

What later patents protected Zytiga?

The most important later protection involved formulations designed to improve the bioavailability of abiraterone acetate. Zytiga originally required administration under fasting conditions because food materially increases abiraterone exposure. Later patents addressed lower-dose formulations and administration conditions.

A key later patent is U.S. Patent No. 8,822,438, directed to pharmaceutical compositions containing abiraterone acetate. That patent became more commercially significant than Patent 5,604,213 after the original compound patent expired.[3]

Secondary patent categories included:

Patent category	Protection strategy
Formulation patents	Lower-dose tablets and excipient combinations
Food-effect patents	Administration with or without food
Method-of-use patents	Prostate cancer treatment and androgen-deprivation combinations
Dosage patents	Specific dosing regimens
Manufacturing patents	Crystallization, purification, and production processes
Salt and solid-state patents	Alternative forms and physical properties

These rights are narrower than the original genus claim. They generally require proof that a generic product or labeling instruction practices the claimed formulation, dosage, or method.

How strong was the original patent estate?

The original estate was commercially strong during its enforceable term because it combined composition, prodrug, method, and formulation claims in one patent.

Strengths

• Claim 8 named abiraterone acetate directly.
• Claim 4 named abiraterone directly.
• The broad genus in claim 1 reached numerous analogues.
• Method claims covered prostate and breast cancer.
• Composition claims supported product-level infringement theories.
• The compound had a distinctive steroid-pyridyl structure with limited design-around value for an identical active ingredient.

Weaknesses

• The Markush genus was unusually broad.
• The claim language, as reproduced, contains duplication and apparent transcription defects.
• Broad genus claims face written-description and enablement scrutiny.
• Excluded compounds suggest prosecution pressure from prior art.
• Method claims could be avoided through labeling strategies, non-infringing indications, or induced-infringement defenses.
• The patent’s commercial value ended with expiration.

For historical purposes, the estate was stronger against a direct abiraterone acetate launch than against structurally remote CYP17 inhibitors. For current purposes, patent strength is zero for blocking generic entry because the patent is expired.

Which companies challenged or entered the abiraterone market?

Generic competition followed the expiration of the original patent and regulatory exclusivity. Companies that received U.S. approvals or commercialized generic abiraterone products have included major generic manufacturers such as:

• Teva Pharmaceuticals;
• Amneal Pharmaceuticals;
• Dr. Reddy’s Laboratories;
• Zydus Pharmaceuticals;
• Cipla;
• Hikma and other ANDA sponsors or distributors.

The competitive market has two principal products:

• 250 mg abiraterone acetate tablets;
• 500 mg abiraterone acetate tablets.

Generic products generally compete on price, supply reliability, formulary placement, and tablet strength. The product is a small-molecule generic, not a biosimilar, so applicants use the ANDA pathway rather than the abbreviated biologics pathway.

Is there biosimilar risk for abiraterone?

No. Abiraterone acetate is a chemically synthesized small molecule. Biosimilar regulation under the Public Health Service Act does not apply.

The relevant regulatory risks are:

• ANDA approval;
• Paragraph IV certifications;
• Orange Book patent listings;
• Labeling carve-outs;
• Formulation patents;
• Manufacturing and supply controls.

The relevant market risk is generic substitution, not biosimilar substitution.

What generic-entry risks remain?

The original patent does not create current entry risk. Remaining risks historically arose from secondary patents and regulatory exclusivity.

Product-level risk

A generic tablet that contains abiraterone acetate in the same dosage form may face infringement allegations under formulation claims. The outcome depends on:

• Exact excipients;
• Particle size;
• Manufacturing process;
• Tablet composition;
• Dissolution profile;
• Proposed labeling;
• Whether the generic product practices a claimed food-effect or dosing limitation.

Method-of-use risk

A generic label may omit patented indications or dosing instructions under a section viii carve-out. That strategy does not eliminate all risk if the remaining label encourages an infringing use.

Manufacturing risk

Manufacturing patents can matter even where the final product does not infringe a composition claim. Process claims may be asserted against API manufacturers, although their value depends on proof that the accused process practices each limitation.

How does abiraterone compare with competing androgen-pathway drugs?

Drug	Target	Patent position	Generic or biosimilar risk
Abiraterone acetate	CYP17 androgen biosynthesis inhibitor	Original compound patent expired; later formulation patents were more relevant	High generic competition
Enzalutamide	Androgen-receptor signaling inhibitor	Separate composition and method estate	Small-molecule generic risk
Apalutamide	Androgen-receptor inhibitor	Later-generation patent estate	Small-molecule generic risk
Darolutamide	Androgen-receptor inhibitor	More recent patent protection	Later generic-entry risk
Docetaxel	Microtubule inhibitor	Legacy generic product	Established generic competition

Abiraterone’s commercial advantage was tied to its distinct mechanism and combination use with androgen-deprivation therapy and prednisone. Its patent disadvantage is that the core compound patent is now expired and the molecule is readily amenable to ordinary generic manufacture.

What is the current commercial exposure?

Zytiga generated multibillion-dollar revenue before generic erosion. Johnson & Johnson reported strong Zytiga sales before U.S. generic entry, but revenue declined after generic abiraterone products entered the market.[4]

The principal exposure points are:

• U.S. branded Zytiga volume;
• Generic price erosion;
• International patent-term differences;
• Formulation-patent enforcement;
• Hospital and specialty-pharmacy contracting;
• Supply concentration for abiraterone API.

The original patent no longer supports premium pricing. Any residual brand value depends on clinical familiarity, supply contracts, patient assistance, and formulation or dosing differentiation.

What is the geographic patent position?

Patent rights are territorial. U.S. Patent 5,604,213 has no direct legal effect outside the United States.

Relevant geographic questions include:

• Whether corresponding foreign patents issued;
• Whether foreign patents had different terms;
• Whether supplementary protection certificates were obtained in Europe;
• Whether local generic approval depended on data exclusivity;
• Whether formulation patents survived in each market.

The U.S. market is mature and genericized. Foreign markets may have had different entry dates because of national patent prosecution, supplementary protection certificates, regulatory exclusivity, and local litigation.

Key Takeaways

• Patent 5,604,213 is the foundational U.S. abiraterone patent.
• Claim 8 expressly covers abiraterone acetate.
• Claim 4 expressly covers abiraterone.
• Claim 1 is a broad Markush genus covering numerous pyridyl-substituted steroid analogues.
• Claims 2, 16, and 17 cover treatment of androgen- or estrogen-dependent disorders, including prostate and breast cancer.
• Claims 9-15 and 22 cover pharmaceutical compositions and dosage forms.
• The patent is expired and no longer blocks generic abiraterone entry.
• Later formulation patents, particularly those directed to abiraterone acetate tablets and dosing conditions, were more relevant after the original patent expired.
• Abiraterone is a small molecule, so the competitive pathway is ANDA approval, not biosimilar approval.
• Current commercial risk is generic price erosion and secondary-patent enforcement, not the original composition patent.

FAQs

Does Patent 5,604,213 cover Zytiga?

Yes. Claim 8 expressly covers 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene, the active ingredient in Zytiga.

Does the patent cover abiraterone hydrochloride?

The claims cover abiraterone in free-base form and pharmaceutically acceptable acid-addition salts. A specific salt may fall within the claims if it satisfies the structural limitations.

Can a generic company avoid claim 8 by using abiraterone rather than abiraterone acetate?

Yes, abiraterone and abiraterone acetate are different chemical entities. However, abiraterone itself is separately covered by the compound claims, including claim 4, and regulatory approval would require an appropriate product and clinical basis.

Is abiraterone acetate still protected by any U.S. patent?

The original compound patent is expired. Separate later patents may have covered formulations, dosage regimens, or manufacturing methods. Their scope must be assessed independently from Patent 5,604,213.

Was Patent 5,604,213 a composition-of-matter patent?

Yes. Its principal claims cover chemical compounds, including abiraterone and abiraterone acetate, in addition to therapeutic methods and pharmaceutical compositions.

References

1. United States Patent and Trademark Office. (1997). U.S. Patent No. 5,604,213, 17-substituted steroids.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Abiraterone acetate. Orange Book.
3. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,822,438, pharmaceutical compositions comprising abiraterone acetate.
4. Johnson & Johnson. (Various years). Annual report and Form 10-K disclosures concerning Zytiga sales and patent litigation.

Drugs Protected by US Patent 5,604,213

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

Foreign Priority and PCT Information for Patent: 5,604,213

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9207057	Mar 31, 1992
United Kingdom	9224880	Nov 27, 1992
United Kingdom	9320132	Sep 30, 1993
United Kingdom	9414192	Jul 14, 1994

International Family Members for US Patent 5,604,213

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0633893		C300508	Netherlands
European Patent Office	0633893		CA 2011 00035	Denmark
European Patent Office	0633893		91911	Luxembourg
European Patent Office	0633893		1190040-4	Sweden
European Patent Office	0633893		C00633893/01	Switzerland
European Patent Office	0633893		11C0055	France