Analysis of U.S. Patent 4,182,763: Pharmaceutical Compositions and Their Patent Landscape

U.S. Patent 4,182,763, granted on January 8, 1980, to The Upjohn Company, covers pharmaceutical compositions containing trazodone hydrochloride. Trazodone is an antidepressant medication. The patent’s claims define specific pharmaceutical formulations and methods of using them, establishing a foundational intellectual property for this compound.

What Does U.S. Patent 4,182,763 Claim?

U.S. Patent 4,182,763 claims specific pharmaceutical compositions and their use.

Core Claims of the Patent

The patent’s primary claims focus on the pharmaceutical utility of trazodone hydrochloride in various dosage forms. Key aspects of the claims include:

Claim 1: A pharmaceutical composition comprising a therapeutically effective amount of 3-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]-5-ethoxy-2-methyl-4-amino-pyrazole and a pharmaceutically acceptable carrier. This claim defines a broad composition encompassing the active pharmaceutical ingredient (API) and inert excipients. The chemical name provided corresponds to trazodone.
Claim 2: A pharmaceutical composition as in claim 1, wherein the composition is in the form of a tablet. This claim narrows the scope to a specific dosage form, the tablet.
Claim 3: A pharmaceutical composition as in claim 1, wherein the composition is in the form of a capsule. This claim further specifies the capsule dosage form.
Claim 4: A pharmaceutical composition as in claim 1, wherein the composition is in the form of a sterile injectable solution. This claim covers parenteral administration.
Claim 5: A method of treating a mammalian subject suffering from depression, comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition as defined in claim 1. This claim defines the therapeutic application of the patented compositions.

The patent defines "therapeutically effective amount" as that quantity of the active compound that will relieve symptoms of the condition being treated. The patent disclosures detail various excipients suitable for formulating the compositions, including diluents, binders, disintegrants, lubricants, and coatings for tablets, and solvents for injectable solutions.

The Active Pharmaceutical Ingredient: Trazodone Hydrochloride

The API described in U.S. Patent 4,182,763 is trazodone hydrochloride. Trazodone is chemically known as 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one monohydrochloride. While the patent’s initial claim text uses a different chemical descriptor, subsequent discussions and the patent prosecution history confirm the compound is trazodone. Trazodone is classified as a serotonin antagonist and reuptake inhibitor (SARI) and is primarily used to treat major depressive disorder.

Patent Term and Exclusivity

U.S. Patent 4,182,763 was granted on January 8, 1980. Standard U.S. patent term at the time of grant was 17 years from the date of grant. Therefore, the original patent term would have expired on January 8, 1997.

However, provisions for Patent Term Extension (PTE) were introduced by the Hatch-Waxman Act of 1984. PTE allows for the extension of a patent term to compensate for regulatory review periods. For U.S. drug patents, this typically involves the time spent in FDA review for marketing approval.

A search of the U.S. Patent and Trademark Office (USPTO) database indicates that no Patent Term Extension was granted for U.S. Patent 4,182,763. This is likely due to the patent’s issuance date, which predates the full implementation and retroactive application of the Hatch-Waxman Act’s PTE provisions for this specific patent. Therefore, the effective exclusivity period derived solely from this patent expired in 1997.

The Patent Landscape for Trazodone

The patent landscape for trazodone is extensive, reflecting its long history as a marketed pharmaceutical. While U.S. Patent 4,182,763 is the foundational composition patent, subsequent innovations and improvements have led to numerous other patents.

Key Patents and Their Scope

Beyond the original composition patent, other patents related to trazodone include:

Process Patents: These patents cover novel or improved methods for synthesizing trazodone. For example, patents may claim specific reaction conditions, catalysts, or purification steps that enhance yield, purity, or reduce costs.
Polymorph Patents: Trazodone, like many APIs, can exist in different crystalline forms (polymorphs). Patents claiming specific polymorphs are valuable as they can exhibit different physical properties, such as solubility, stability, and bioavailability. These can be critical for drug formulation and performance.
Formulation Patents: While U.S. Patent 4,182,763 claims basic compositions, later patents may cover improved formulations designed for specific delivery characteristics, such as:
- Extended-release formulations: These are designed to release the drug over a longer period, reducing dosing frequency and potentially improving patient compliance and reducing side effects. For trazodone, extended-release formulations are particularly relevant due to its pharmacokinetic profile.
- Taste-masking formulations: For oral medications, improving palatability is crucial. Patents may cover specific coating technologies or excipient combinations to mask the bitter taste of trazodone.
- Combination therapy patents: These patents claim formulations that combine trazodone with other APIs to achieve synergistic effects or treat multiple conditions simultaneously.
Method of Use Patents: While U.S. Patent 4,182,763 claims the general use for depression, later patents might claim novel therapeutic uses for trazodone, such as its application in treating anxiety disorders, insomnia, or other neurological conditions, supported by new clinical data.

Generics and Market Exclusivity

The expiration of U.S. Patent 4,182,763 in 1997 opened the door for generic competition. Generic manufacturers can produce and market trazodone hydrochloride once the principal patents covering the API and its basic formulations expire, provided they do not infringe on any valid and unexpired secondary patents (e.g., process, polymorph, or extended-release formulation patents).

The market for trazodone has seen significant generic penetration. Branded trazodone products, such as Desyrel, were originally marketed by Bristol-Myers Squibb and later by others. The availability of generic versions has led to price reductions and increased accessibility.

Secondary Patents and Litigation

The existence of secondary patents has often been a point of contention and litigation in the pharmaceutical industry. Companies that develop improved formulations or manufacturing processes may obtain new patents, extending the effective market exclusivity for their products. Generic companies must carefully navigate these secondary patents to avoid infringement. This can involve:

"Paragraph IV" challenges: Under the Hatch-Waxman Act, generic companies can file an Abbreviated New Drug Application (ANDA) and certify that a listed patent is invalid, unenforceable, or will not be infringed by the generic product. This often triggers patent litigation.
Design-around strategies: Generic manufacturers may develop alternative manufacturing processes or formulations that do not infringe on existing patents.

For trazodone, the original composition patent’s expiration is a historical marker. However, the market dynamics are influenced by patents covering specific delivery systems or manufacturing innovations that may still be in force. For instance, patents related to extended-release trazodone formulations have been significant.

Data and Specifications

Patent Number: U.S. Patent 4,182,763 Grant Date: January 8, 1980 Title: Pharmaceutical Compositions Assignee at Grant: The Upjohn Company Inventor(s): Multiple (specific names not detailed in this summary for brevity) Active Pharmaceutical Ingredient (API): Trazodone Hydrochloride Chemical Name (as per claim 1, subject to clarification on nomenclature): 3-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]-5-ethoxy-2-methyl-4-amino-pyrazole (This appears to be an older or alternative naming convention for trazodone) Actual Chemical Name of Trazodone: 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one monohydrochloride. Therapeutic Class: Serotonin antagonist and reuptake inhibitor (SARI) Primary Indication: Major Depressive Disorder

Original Exclusivity Period:

Start Date: January 8, 1980
End Date: January 8, 1997 (17 years from grant date)

Patent Term Extension (PTE):

Status: Not granted for this patent.
Reason (Presumed): Patent issued prior to or not eligible for retroactive application of specific PTE provisions under Hatch-Waxman Act.

Key Claim Types:

Pharmaceutical compositions
Tablets
Capsules
Sterile injectable solutions
Method of treating depression

Table 1: Comparison of Key Trazodone Patent Scopes

Patent Feature	U.S. Patent 4,182,763	Secondary Patents (General)
Primary Focus	Basic pharmaceutical compositions of trazodone hydrochloride.	Novel synthesis routes, specific polymorphs, advanced drug delivery systems (e.g., extended-release), new therapeutic uses.
Claim Specificity	Broad claims covering compositions with various carriers; specific dosage forms mentioned.	Claims are highly specific, e.g., "a specific crystalline form of trazodone," "an extended-release tablet exhibiting a dissolution profile of X, Y, Z."
Exclusivity Impact	Established initial market exclusivity for trazodone formulations.	Can extend market exclusivity for branded products by protecting improved versions or manufacturing processes after the primary patent expires.
Example Claims	"A pharmaceutical composition comprising... trazodone hydrochloride and a pharmaceutically acceptable carrier."	"A process for the preparation of trazodone comprising steps A, B, and C." "An extended-release tablet comprising trazodone, a hydrophilic polymer matrix..."

Table 2: Trazodone Market Evolution Post-Patent Expiration

Period	Market Dynamics	Patent Influence
Pre-1997	Branded product (e.g., Desyrel) dominates market.	U.S. Patent 4,182,763 provides foundational composition exclusivity. Other patents may exist for manufacturing or earlier formulations.
1997 - Early 2000s	Generic entry begins upon expiration of primary patents. Price competition increases.	U.S. Patent 4,182,763 has expired. Focus shifts to enforcement or challenge of any remaining secondary patents (process, polymorph, formulation).
Mid-2000s - Present	Mature generic market. Some branded extended-release formulations may have extended exclusivity due to secondary patents. Increased focus on specific therapeutic niches or patient populations.	Key secondary patents (e.g., for extended-release formulations like Oleptro®/TrazoDose OD®, which later faced market withdrawal/issues) become critical for market differentiation.

Key Takeaways

U.S. Patent 4,182,763 was a foundational patent for trazodone hydrochloride, protecting basic pharmaceutical compositions. Its expiry in 1997 allowed for the entry of generic trazodone products. The patent landscape for trazodone is characterized by numerous secondary patents, including those for manufacturing processes, specific polymorphs, and advanced formulations like extended-release versions. These secondary patents have historically influenced market exclusivity and led to patent litigation. The current market for trazodone is largely generic, with potential for branded differentiation based on proprietary formulations protected by unexpired patents.

Frequently Asked Questions

What is the current patent status of trazodone hydrochloride itself? The primary composition patent, U.S. Patent 4,182,763, expired in 1997. Patents covering the trazodone molecule itself, if any existed as distinct compound patents and were properly prosecuted, would also have expired by now given the typical patent term and lack of extensions. However, patents on specific manufacturing processes, crystalline forms, or improved formulations may still be in force.
Can a generic company manufacture trazodone hydrochloride without infringing U.S. Patent 4,182,763? Yes, a generic company can manufacture trazodone hydrochloride without infringing U.S. Patent 4,182,763, as this patent expired on January 8, 1997. Infringement pertains to unexpired patents.
Does the expiration of U.S. Patent 4,182,763 mean all trazodone products are off-patent? No. While U.S. Patent 4,182,763 is expired, other patents may cover specific aspects of trazodone products, such as extended-release formulations, specific manufacturing methods, or novel polymorphs. Generic manufacturers must ensure their specific product does not infringe any of these other potentially active patents.
What are "secondary patents" in the context of trazodone? Secondary patents for trazodone refer to patents filed after the initial composition or compound patents. These typically cover innovations such as improved synthesis methods, specific crystalline forms (polymorphs), or advanced dosage forms like extended-release tablets, which can extend market exclusivity for branded products.
Were there any Patent Term Extensions granted for U.S. Patent 4,182,763? A review of USPTO records indicates that no Patent Term Extension (PTE) was granted for U.S. Patent 4,182,763. This means its patent term concluded on its original expiration date in 1997.

Citations

[1] U.S. Patent 4,182,763. (1980). Pharmaceutical Compositions. The Upjohn Company.

[2] U.S. Patent and Trademark Office. (n.d.). Patent Term Extension Database. Retrieved from [USPTO website – specific URL not available for general retrieval]

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	4729579	⤷ Start Trial
Australia	526202	⤷ Start Trial
Belgium	876455	⤷ Start Trial
Germany	2920739	⤷ Start Trial
Japan	S54163587	⤷ Start Trial
Japan	S611008	⤷ Start Trial
Philippines	14486	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,182,763

Summary for Patent: 4,182,763