Details for Patent: 6,015,819

Summary for Patent: 6,015,819

Title:	Use of alpha-1C specific compounds to treat benign prostatic hyperplasia
Abstract:	PCT No. PCT/US93/10950 Sec. 371 Date Apr. 1, 1997 Sec. 102(e) Date Apr. 1, 1997 PCT Filed Nov. 12, 1993 PCT Pub. No. WO94/10989 PCT Pub. Date May 26, 1994A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human alpha 1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human alpha 1A adrenergic receptor, a human alpha 1B adrenergic receptor, and a human histamine H1 receptor, and, binds to a human alpha 2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such alpha 1C adrenergic receptor. Compounds meeting these criteria are provided.
Inventor(s):	Charles Gluchowski, Carlos C. Forray, George Chiu, Theresa A. Branchek, John M. Wetzel, Paul R. Hartig
Assignee:	H Lundbeck AS
Application Number:	US08/244,354
Patent Claim Types: see list of patent claims	Use;

U.S. Patent 6,015,819: Claim Scope, Patent Strength, Exclusivity and Competitive Landscape

U.S. Patent No. 6,015,819 is a functional, receptor-selectivity patent directed to treating benign prostatic hyperplasia and inhibiting prostatic contraction with an antagonist selective for the human α1C adrenergic receptor. Its claims do not require a particular chemical compound, dosage form, formulation, salt, crystal form, manufacturing process, or brand product. The principal limitations are receptor-binding ratios and the requirement that treatment not cause an orthostatic fall in blood pressure.

The patent’s commercial significance depends on whether a marketed antagonist satisfies the specified binding-affinity thresholds and the blood-pressure limitation. Because the patent claims are method claims and the patent issued in 2000, its enforceable term has ended under the standard U.S. patent-term framework, subject to the recorded term calculation and any patent-term adjustment.[1][2]

What does U.S. Patent 6,015,819 protect?

The patent protects two related categories of activity:

1. Treating benign prostatic hyperplasia in a subject.
2. Inhibiting contraction of prostatic tissue.

Both categories require use of an antagonist that meets specified selectivity criteria for the human α1C adrenergic receptor and does not cause an orthostatic fall in blood pressure.[1]

The patent is therefore a target-profile patent. It attempts to capture any antagonist, regardless of chemical structure, that produces the claimed pharmacological relationship.

Claim architecture

Claim group	Subject matter	Principal threshold
Claims 1-29	Treatment of benign prostatic hyperplasia	α1C/α1B affinity ratio of at least 48:1 or 26:1, depending on independent claim
Claims 30-38	Inhibition of prostatic tissue contraction	α1C/α1B affinity ratio of at least 48:1 or 200:1
Claims 39-58	Narrower prostatic-contraction methods	α1C/α1B ratio of at least 26:1, 35:1 or 200:1
Claims 29 and 58	Rat blood-pressure limitation	No orthostatic fall at 10 micrograms/kg

The claims are highly repetitive. Claims 30-58 largely duplicate claims 1-29 while changing the claimed activity from treatment of BPH to inhibition of prostatic tissue contraction.

How broad are the independent claims?

Claims 1, 10, 13, 30, 39 and 42 are the principal independent claims.

Claims 1 and 30

These claims require:

• An antagonist binding to human α1C adrenergic receptors.
• An α1C-to-α1B binding-affinity ratio of at least 48:1.
• A therapeutically effective amount for claim 1, or an effective contraction-inhibiting amount for claim 30.
• No orthostatic fall in blood pressure.

The word “antagonist” is structurally broad. A claim to an antagonist defined by pharmacological activity can cover multiple chemical classes if the accused compound satisfies the binding and physiological limitations.

Claims 10 and 39

These claims reduce the α1C-to-α1B threshold to 26:1. That makes them broader than claims 1 and 30 on the primary receptor-selectivity requirement.

The broader threshold may improve coverage of compounds with meaningful but less extreme α1C selectivity. It also creates greater exposure to prior-art and enablement challenges because more compounds may fall within the claimed functional class.

Claims 13 and 42

These claims require:

• At least 35-fold greater binding affinity for α1C than α1A.
• At least 417-fold greater binding affinity for α1C than histamine H1.
• No orthostatic fall in blood pressure.

They are narrower than claims 1 and 10 because they impose multiple quantitative selectivity thresholds. A product that fails any one of the ratios falls outside the claim.

What receptor selectivity does the patent require?

The patent uses several pharmacological selectivity screens. The main required comparisons are against:

• Human α1B adrenergic receptors.
• Human α1A adrenergic receptors.
• Human α2 adrenergic receptors.
• Human histamine H1 and H2 receptors.
• Calcium channels.
• Dopamine D2, D3, D4 and D5 receptors.
• Serotonin receptors.

The dependent claims require α1C selectivity ranging from 10-fold to 871-fold, depending on the comparator.

Comparator	Lowest stated ratio	Highest stated ratio
α1B adrenergic receptor	26-fold	200-fold
α1A adrenergic receptor	10-fold	776-fold
α2 adrenergic receptor	10-fold	871-fold
Histamine H1 receptor	10-fold	417-fold
Histamine H2 receptor	25-fold	324-fold
Calcium channel	10-fold	550-fold
Serotonin receptor	10-fold	74-fold
Dopamine D2, D3, D4 or D5 receptor	10-fold	Not specified beyond the dependent threshold

The relevant measurement is comparative binding affinity, not simply whether the compound binds to α1C. The claims require a ratio between binding results for different biological targets.

Historical receptor nomenclature is material

The claims separately identify α1C and α1A receptors. Modern pharmacology may use different nomenclature or classify receptor subtypes differently from the terminology used during prosecution. The patent specification, cited assay methods, prosecution history and expert testimony would therefore be important in determining whether the claimed receptor labels refer to historical receptor classifications, cloned human receptors, or a particular assay construct.

A modern assay using a receptor labeled α1A may not automatically establish the α1C result required by the patent. The exact assay system, ligand, cell line, tissue preparation and calculation method can affect the ratio.

What is the strongest claim in the patent?

The strongest claim depends on the accused product.

For a highly selective compound, claims 8, 16, 20, 22, 28, 37, 45, 49, 51 and 57 are potentially the most commercially relevant because they require an α1C-to-α1B ratio of at least 200:1 and impose additional selectivity thresholds.

For a compound with moderate α1C selectivity, claims 10 and 39 are the principal exposure points because they use the lower 26:1 threshold.

For a compound with documented separation from α1A and histamine H1 receptors, claims 13 and 42 may provide narrower but technically specific coverage.

The claims are cumulative. A product may fall within several claims simultaneously if its assay profile exceeds multiple thresholds.

What formulations are protected by U.S. Patent 6,015,819?

The patent claims do not expressly require or protect:

• Extended-release tablets.
• Immediate-release tablets.
• Capsules.
• Oral solutions.
• Injectable formulations.
• Transdermal systems.
• Particular excipients.
• Specific particle sizes.
• Polymorphs or hydrates.
• Salts or solvates.
• Combination products.
• Manufacturing processes.

The claims cover administration or tissue contact using an antagonist with the stated pharmacological profile. A formulation could be relevant only because it delivers a compound that satisfies the method limitations. A separate formulation patent would be needed to protect release characteristics, dosage-form architecture or excipient composition.

What method-of-use protection does the patent provide?

The patent has two principal method-of-use positions.

BPH treatment

Claims 1-29 require treatment of benign prostatic hyperplasia. A commercial product used for BPH could implicate these claims if the receptor ratios and blood-pressure limitation are met.

Prostatic contraction

Claims 30-58 cover contacting prostate tissue with an effective contraction-inhibiting amount. These claims are directed to a biological effect rather than the clinical diagnosis alone.

The tissue-contacting language may have narrower practical application than the BPH claims. It could be relevant to ex vivo testing, research use or experimental procedures, but commercial infringement would depend on how the claim is construed and whether the accused activity qualifies as contacting prostate tissue.

When did U.S. Patent 6,015,819 lose exclusivity?

The patent issued on January 18, 2000.[1] Under 35 U.S.C. §154, a U.S. utility patent generally expires 20 years after the effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and limited statutory extensions.[2]

Because the patent issued before 2000, its ordinary 20-year term necessarily ended no later than 20 years after its pre-issuance filing date. The patent therefore does not provide live U.S. exclusionary rights in 2026 under the standard term calculation.

The patent is not a pharmaceutical composition patent and would not ordinarily support patent-term extension under 35 U.S.C. §156. A regulatory exclusivity period, if any existed for a separately approved drug, would not revive an expired method patent.[3]

What is the Orange Book status of U.S. Patent 6,015,819?

The patent claims a pharmacological method of treating BPH and inhibiting prostatic contraction. They do not claim an active ingredient, drug product, dosage form or formulation.

An Orange Book listing would depend on whether the patent was submitted for an approved product and whether it met FDA listing criteria. The claim text alone does not establish an Orange Book listing. If the patent was never listed against an approved product, it would not have supported an Orange Book Paragraph IV certification.

Even if it had been listed historically, expiration removes the patent as a current barrier to generic approval. FDA regulatory exclusivity and patent expiry are separate issues.[3][4]

How would a generic Paragraph IV challenge apply?

A generic applicant could have used a Paragraph IV certification if the patent had been listed against the relevant reference-listed drug and the applicant’s labeling implicated the patented BPH method.[4]

The principal defenses would have included:

• Non-infringement because the drug does not meet the receptor ratios.
• Failure to satisfy the “no orthostatic fall” limitation.
• Invalidity for lack of written description or enablement.
• Obviousness based on known α1-adrenergic antagonists and BPH treatment.
• Indefiniteness concerning binding-affinity methodology or the meaning of orthostatic fall.
• Lack of a direct infringement theory if the proposed labeling omits the patented use.

A standard ANDA carve-out could reduce risk if the patented use were separable from the approved labeling. That strategy would be less effective if BPH treatment were the central or unavoidable labeled use.

How strong is the patent estate?

The patent’s claim breadth is high in chemical terms but lower in proof and enforceability terms.

Factor	Assessment
Chemical scope	Broad because no specific molecular structure is required
Pharmacological scope	Narrowed by quantitative receptor ratios
Clinical scope	Limited to BPH and prostatic contraction
Formulation scope	None apparent
Manufacturing scope	None apparent
Proof burden	High because multiple receptor assays may be required
Claim construction risk	High because α1C nomenclature and affinity methodology matter
Current enforceability	None after expiration
Biosimilar relevance	None
Generic relevance	Historical method-of-use relevance only

The strongest commercial weakness is the need to prove exact receptor-affinity ratios. Binding affinity can vary with assay conditions, receptor expression systems, radioligands and statistical treatment. A patent owner would need reliable evidence that the accused antagonist meets the applicable ratio in the relevant human-receptor assay.

The “does not cause an orthostatic fall in blood pressure” limitation also creates proof issues. The claims do not specify a universally applicable clinical threshold, duration, patient population or measurement protocol. Claims 29 and 58 add a rat dose of 10 micrograms/kg, but the animal limitation does not automatically establish the human clinical result.

Which companies and drugs are most relevant?

The claims potentially reach α1-adrenergic antagonists used for BPH, but they do not identify a commercial compound. Relevant competitive products historically include:

Drug	Typical BPH positioning	Relevance to the patent
Tamsulosin	α1A/α1D-oriented BPH therapy	Requires comparison against the patent’s α1C terminology and ratios
Alfuzosin	Uroselective α1 antagonist	Requires receptor-affinity testing and orthostatic assessment
Silodosin	Highly α1A-selective BPH therapy	May face nomenclature and ratio issues because the patent separately identifies α1A and α1C
Doxazosin	Nonselective α1 antagonist	Less likely to satisfy the high selectivity thresholds
Terazosin	Nonselective α1 antagonist	Less likely to satisfy the high selectivity thresholds
Naftopidil	α1 antagonist with additional receptor activity	Requires testing against the listed off-target receptors

This comparison is not a determination that any product infringed or fell within the claims. The claims cannot be mapped conclusively to a marketed drug without validated receptor-binding data and product-specific clinical evidence.

What litigation, licensing deals and settlements affect the patent?

The claim text does not identify litigation, licensing agreements or settlement terms. No such transaction can be inferred from the claims.

Because the patent has reached the end of its ordinary term, historical litigation would have greater relevance than current launch risk. Any surviving contractual license could remain commercially relevant even after patent expiry, but a license would not extend statutory patent exclusivity unless supported by separate contractual restrictions.

What generic launch risks exist today?

The direct patent risk is effectively zero after expiry. Current competitors would instead face:

• FDA approval requirements.
• Active patents in later portfolios.
• Formulation or controlled-release patents.
• Salt, polymorph or crystal-form patents.
• Manufacturing-process patents.
• Labeling restrictions.
• Regulatory exclusivity attached to a particular reference product.
• Trade-secret or know-how barriers.

U.S. Patent 6,015,819 does not itself create a current barrier to a generic BPH product. It also does not create biosimilar risk because it concerns a small-molecule pharmacological method rather than a biologic.

Key Takeaways

• U.S. Patent 6,015,819 is a functional method-of-use patent for α1C-selective antagonists in BPH.
• It covers treatment and prostatic-tissue contraction inhibition, not a specific chemical compound.
• The central limitations are quantitative receptor-binding ratios and absence of orthostatic blood-pressure effects.
• Claims 10 and 39 are the broadest principal claims because they use a 26:1 α1C-to-α1B threshold.
• Claims 13, 20, 42 and 49 are narrower because they impose multiple high selectivity thresholds.
• The patent has no apparent formulation, composition or manufacturing claims.
• The patent’s ordinary U.S. term ended before 2026 under the 20-year patent-term framework.
• It has no current biosimilar significance and presents no current generic launch barrier.
• Historical infringement analysis would require receptor-specific assay data, clinical blood-pressure data and prosecution-history review.
• The α1C versus α1A nomenclature issue is central to claim construction and product mapping.

FAQs

Does U.S. Patent 6,015,819 claim tamsulosin specifically?

No. The claims do not name tamsulosin or any other chemical compound. Coverage depends on whether a product satisfies the claimed receptor-affinity ratios and blood-pressure limitation.

Can a receptor-binding assay alone establish infringement?

Usually, no. The method claims also require the specified BPH or prostatic-contraction use, an effective amount, and absence of an orthostatic fall in blood pressure. Receptor data would address only part of the claim.

Does the patent cover a combination of an α1 antagonist with a 5-alpha-reductase inhibitor?

Not expressly. The claims do not recite combination therapy. A combination could raise separate infringement questions only if the claimed antagonist and all other limitations were satisfied.

Could the patent block an over-the-counter BPH product?

No current statutory block arises from this expired patent. Any present barrier would need to come from another unexpired patent, regulatory requirement or proprietary right.

Are α1C and α1A interchangeable for patent purposes?

Not automatically. The claims treat them as separate receptors. The patent specification, prosecution record and applicable assay definitions would control the analysis.

References

[1] United States Patent and Trademark Office. (2000). U.S. Patent No. 6,015,819. Washington, DC: U.S. Department of Commerce.

[2] 35 U.S.C. § 154 (2024).

[3] 35 U.S.C. § 156 (2024).

[4] U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th ed. Washington, DC: U.S. Department of Health and Human Services.

Drugs Protected by US Patent 6,015,819

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: 6,015,819

PCT Information
PCT Filed	November 12, 1993	PCT Application Number:	PCT/US93/10950
PCT Publication Date:	May 26, 1994	PCT Publication Number:	WO94/10989

International Family Members for US Patent 6,015,819

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2240495
Australia	5602994
Australia	680457
Australia	700304
Australia	7684894
Canada	2148839
Canada	2187773