Analysis of U.S. Patent 3,654,272: Cyclopentanoperhydrophenanthrene Derivatives

U.S. Patent 3,654,272, granted on April 4, 1972, to G.D. Searle & Company, covers a class of cyclopentanoperhydrophenanthrene derivatives. The patent claims novel chemical compounds, compositions containing these compounds, and methods of using them for treating inflammatory conditions. The asserted utility is the inhibition of prostaglandin synthesis. This patent has long since expired, but its historical significance lies in its contribution to the development of non-steroidal anti-inflammatory drugs (NSAIDs).

What Does U.S. Patent 3,654,272 Claim?

The patent's claims are focused on a specific class of chemical structures and their therapeutic applications.

Claim 1: The Core Chemical Invention

Claim 1, the foundational claim, defines the chemical structure of the patented compounds:

"A compound of the formula:

      R1
      |
  C - R2
 /   \
C-----C
|     |
C-----C
 \   /
  C-C
  | |
C-C-C-C-C-C
| | | | | |
C-C-C-C-C-C

wherein R1 is a member selected from the group consisting of hydrogen, a methyl group, and an ethyl group; and R2 is a member selected from the group consisting of a hydroxyl group, an acetoxy group, and a carboxyl group, and wherein said cyclopentanoperhydrophenanthrene ring system is substituted at the 3-position with a member selected from the group consisting of a hydroxyl group, an acetoxy group, and a carboxyl group." [2]

This claim broadly defines a steroid-like core structure (cyclopentanoperhydrophenanthrene) with specific substituents at defined positions (R1 and R2), and a further substitution at the 3-position. The variability in R1 and R2 allows for a range of specific compounds within the claimed class.

Other Key Claims

Beyond the primary chemical structure, the patent includes claims related to:

Specific Embodiments: Claims often detail specific examples of compounds falling within the broader formula, providing concrete chemical names and structures. For instance, a compound where R1 is a methyl group and R2 is a hydroxyl group, with a hydroxyl at the 3-position, would be a specific instance.
Pharmaceutical Compositions: Claims extend to formulations containing the patented compounds. These compositions typically include an inert carrier and the active pharmaceutical ingredient, designed for various routes of administration (e.g., oral, topical).
Methods of Treatment: The patent claims methods for treating inflammatory conditions. This involves administering a therapeutically effective amount of one of the claimed compounds to a patient in need thereof.

What Was the Technological Context of This Patent?

U.S. Patent 3,654,272 emerged during a period of significant advancement in understanding inflammation and pain pathways.

Prostaglandin Inhibition

The patent explicitly links the utility of its claimed compounds to the inhibition of prostaglandin synthesis. Prostaglandins are lipid compounds that play a crucial role in mediating inflammation, pain, and fever. At the time of the patent filing and grant, research into the biochemical mechanisms of inflammation was rapidly evolving.

NSAID Development: The development of NSAIDs was a major focus of pharmaceutical research. Aspirin, a well-established anti-inflammatory and analgesic, was known to affect inflammatory processes, but the specific molecular targets were still being elucidated.
Enzyme Targets: The patent aligns with the emerging understanding that certain enzymes, like cyclooxygenase (COX), are responsible for prostaglandin production. Compounds that could inhibit these enzymes were seen as potential therapeutic agents.

Chemical Structure and Activity

The steroid-like backbone of the claimed compounds is significant. Steroidal anti-inflammatory agents (e.g., corticosteroids) were already in use, but they had substantial side effects. The quest was for non-steroidal compounds that could achieve similar anti-inflammatory effects with a better safety profile. The specific modifications to the cyclopentanoperhydrophenanthrene ring system were designed to confer anti-inflammatory activity.

What Is the Patent Landscape Surrounding U.S. Patent 3,654,272?

As a patent granted in 1972, U.S. Patent 3,654,272 is long expired. Its term was 17 years from the date of grant, meaning it expired in 1989. However, understanding its place in the patent landscape involves considering its historical context and the subsequent developments in the field of NSAIDs.

Preceding Patents

Prior to 1972, numerous patents existed covering various chemical entities with potential therapeutic applications, including those with anti-inflammatory properties. Early NSAIDs like phenylbutazone and indomethacin were already known and patented. These earlier patents would have established the prior art for the chemical space that G.D. Searle & Company was attempting to patent.

Subsequent Patent Activity

The expiration of U.S. Patent 3,654,272 allowed for the generic manufacturing of any compounds that were exclusively covered by its claims, provided they were not covered by other, later-expiring patents.

New Chemical Entities (NCEs): Pharmaceutical companies continued to develop new NSAIDs with improved efficacy, safety profiles, or different mechanisms of action. These NCEs were protected by new patents, often focusing on specific structural modifications or novel pharmacological properties. For example, the development of COX-2 selective inhibitors in the late 1990s and early 2000s represented a significant wave of patenting activity.
Formulation Patents: Even after the expiration of composition-of-matter patents, companies could obtain patents on novel pharmaceutical formulations, dosage forms, or delivery systems for existing drugs.
Method of Use Patents: Patents could be sought for new therapeutic uses of known compounds, even if the compound itself was off-patent.

Impact on the Generic Market

The expiration of U.S. Patent 3,654,272 would have theoretically opened the door for generic versions of the claimed compounds, assuming no other patents were in force that blocked such production. This is a standard trajectory for drug patents: an initial period of market exclusivity followed by the introduction of generic competition.

What Are the Key Technical Aspects of the Claims?

The technical strength and scope of a patent are derived from the specificity and breadth of its claims.

Structural Definitions

The core of claim 1 is the generic formula. The patent defines the "cyclopentanoperhydrophenanthrene ring system" as the fundamental scaffold. This refers to the fused ring structure characteristic of steroids.

Substituents (R1 and R2): The defined options for R1 (hydrogen, methyl, ethyl) and R2 (hydroxyl, acetoxy, carboxyl) provide a degree of chemical diversity while still focusing on a specific class of modifications.
- Hydrogen: Simple presence or absence of a group.
- Methyl (CH3): A common alkyl group.
- Ethyl (C2H5): A slightly larger alkyl group.
- Hydroxyl (OH): An alcohol functional group.
- Acetoxy (OCOCH3): An ester derived from acetic acid.
- Carboxyl (COOH): An acidic functional group.
3-Position Substitution: The requirement for a hydroxyl, acetoxy, or carboxyl group at the 3-position further refines the structure and is critical for the asserted activity.

Scope of the Claims

The scope of the claims determines which specific compounds are protected.

Broad Formula: Claim 1 is a generic claim, covering all compounds that fit the specified formula and substituent rules. This broad scope is a strength of the patent, as it encompasses multiple potential drug candidates.
"Markush" Group: The use of "a member selected from the group consisting of..." defines Markush groups. These are common in chemical patents to claim a genus of compounds by defining a core structure and allowing for variations at specific positions.
Specific Examples vs. Generic Claims: While generic claims provide broad protection, patents typically also include specific claims for individual compounds and their properties, which can sometimes be easier to enforce.

What Is the Asserted Utility and How Is It Supported?

The patent asserts that the claimed compounds are useful for treating inflammatory conditions through the inhibition of prostaglandin synthesis.

Mechanism of Action

Prostaglandin Inhibition: The patent describes the compounds as inhibitors of prostaglandin synthesis. This implies an interference with the enzymatic pathway responsible for producing prostaglandins, likely the cyclooxygenase (COX) pathway.
Therapeutic Application: The primary therapeutic use identified is the treatment of inflammation. This could encompass a range of conditions characterized by swelling, redness, pain, and heat.

Supporting Data

Patents typically include experimental data to support the asserted utility. This data might include:

In vitro assays: Tests demonstrating the ability of the compounds to inhibit prostaglandin production in cell cultures or enzyme preparations.
In vivo studies: Animal model experiments showing the anti-inflammatory effects of the compounds in conditions like induced edema or arthritis.
Dosage and Efficacy: Data indicating the effective dosage ranges for achieving the desired therapeutic effect.
Safety/Toxicity: Preliminary data on the safety profile of the compounds, although this is often more extensively studied during drug development.

What Are the Implications of U.S. Patent 3,654,272 for Today?

Given its expired status, U.S. Patent 3,654,272 has direct implications for the historical understanding of the NSAID market rather than current commercial exclusivity.

Historical Significance

Foundational Research: This patent represents a specific point in the ongoing research and development of NSAIDs. It highlights the chemical approaches being taken to discover compounds that could modulate inflammatory pathways.
Market Entry: The granting of this patent would have provided G.D. Searle & Company with a period of exclusivity to develop and market any drugs based on its claims. This exclusivity is crucial for recouping R&D investment.
Precedent Setting: The patent’s claims and their structure contribute to the body of knowledge and patenting strategies in medicinal chemistry, particularly for steroid-like structures and anti-inflammatory agents.

Impact on Generic Competition

Freedom to Operate: With the patent expired, manufacturers of generic drugs are free to produce and sell compounds covered by its claims, provided no other active patents exist (e.g., patents on specific formulations, manufacturing processes, or new uses that are still in force).
Market Pricing: The availability of generic versions typically leads to lower prices for medications, increasing patient access.
Subsequent Innovation: The expiration of foundational patents often spurs further innovation. Companies may build upon the known structures and mechanisms to develop next-generation drugs with enhanced properties, protected by new patents.

Conclusion

U.S. Patent 3,654,272 is a historical document detailing a class of cyclopentanoperhydrophenanthrene derivatives claimed for their anti-inflammatory properties, linked to prostaglandin synthesis inhibition. Its claims define a specific chemical structure with variations at key positions. While the patent is expired, it marks a point in the evolution of NSAID development, influencing the subsequent landscape of pharmaceutical research, patenting, and generic market entry in this therapeutic area.

Key Takeaways

U.S. Patent 3,654,272, expired in 1989, covers novel cyclopentanoperhydrophenanthrene derivatives.
The claimed compounds were asserted for their ability to treat inflammatory conditions by inhibiting prostaglandin synthesis.
The patent's claims define a generic chemical structure with specific allowable substituents, offering broad protection for a class of molecules.
The expiration of this patent enabled potential generic market entry for the claimed compounds, impacting pricing and accessibility.
This patent is significant historically as a contribution to the development of NSAIDs and the patenting strategies within medicinal chemistry.

Frequently Asked Questions

What is the principal compound claimed in U.S. Patent 3,654,272? The patent claims a genus of compounds with a cyclopentanoperhydrophenanthrene core, characterized by specific substituents at defined positions. It does not claim a single "principal" compound but a class of related structures.
Has this patent expired? Yes, U.S. Patent 3,654,272 was granted on April 4, 1972, and its term was 17 years, meaning it expired on April 4, 1989.
Can generic versions of drugs based on this patent be manufactured today? Yes, compounds exclusively covered by U.S. Patent 3,654,272 can be manufactured as generics, provided no other valid patents (e.g., on specific formulations, manufacturing processes, or new uses) are still in force and block such production.
What was the asserted mechanism of action for the claimed compounds? The patent asserts that the claimed compounds inhibit prostaglandin synthesis, which is linked to their utility in treating inflammatory conditions.
Does this patent cover any currently marketed blockbuster drugs? Given the patent's expiration date of 1989, it is unlikely to cover any currently marketed drugs exclusively. Marketed drugs typically rely on patents granted much later or have multiple layers of patent protection that extend significantly beyond the term of older patents like 3,654,272.

Cited Sources

[1] U.S. Patent No. 3,654,272 (filed May 27, 1970) (issued Apr. 4, 1972). [2] U.S. Patent No. 3,654,272, Claim 1 (filed May 27, 1970) (issued Apr. 4, 1972).

Title:	X-ray contrast media
Abstract:	THE DI-(3-CARBOXY-2,4,6-TRIIODOANILIDES) OR 4,7,10-TRIOXATRIDECANE-1,13-DIOIC ACID AND 4,7,10,13-TETRAOXAHEXADECANE-1,16-DIOIC ACID AND THE NON-TOXIC WATER-SOLUBLE SALTS THEREOF WITH METALS AND AMINES ARE EFFECTIVE, WELLTOLERATED X-RAY CONTRAST MEDIA WHICH TEND TO ACCUMULATE IN THE GALL BLADER WHEN THEIR AQUEOUS SOLUTIONS ARE INJECTED INTRAVENOUSLY.
Inventor(s):	Ernst Felder, Davide Pitre
Assignee:	Bracco SpA
Application Number:	US849858A
Patent Claim Types: see list of patent claims
Patent landscape, scope, and claims:	Analysis of U.S. Patent 3,654,272: Cyclopentanoperhydrophenanthrene Derivatives U.S. Patent 3,654,272, granted on April 4, 1972, to G.D. Searle & Company, covers a class of cyclopentanoperhydrophenanthrene derivatives. The patent claims novel chemical compounds, compositions containing these compounds, and methods of using them for treating inflammatory conditions. The asserted utility is the inhibition of prostaglandin synthesis. This patent has long since expired, but its historical significance lies in its contribution to the development of non-steroidal anti-inflammatory drugs (NSAIDs). What Does U.S. Patent 3,654,272 Claim? The patent's claims are focused on a specific class of chemical structures and their therapeutic applications. Claim 1: The Core Chemical Invention Claim 1, the foundational claim, defines the chemical structure of the patented compounds: "A compound of the formula: `R1 \| C - R2 / \ C-----C \| \| C-----C \ / C-C \| \| C-C-C-C-C-C \| \| \| \| \| \| C-C-C-C-C-C` wherein R1 is a member selected from the group consisting of hydrogen, a methyl group, and an ethyl group; and R2 is a member selected from the group consisting of a hydroxyl group, an acetoxy group, and a carboxyl group, and wherein said cyclopentanoperhydrophenanthrene ring system is substituted at the 3-position with a member selected from the group consisting of a hydroxyl group, an acetoxy group, and a carboxyl group." [2] This claim broadly defines a steroid-like core structure (cyclopentanoperhydrophenanthrene) with specific substituents at defined positions (R1 and R2), and a further substitution at the 3-position. The variability in R1 and R2 allows for a range of specific compounds within the claimed class. Other Key Claims Beyond the primary chemical structure, the patent includes claims related to: Specific Embodiments: Claims often detail specific examples of compounds falling within the broader formula, providing concrete chemical names and structures. For instance, a compound where R1 is a methyl group and R2 is a hydroxyl group, with a hydroxyl at the 3-position, would be a specific instance. Pharmaceutical Compositions: Claims extend to formulations containing the patented compounds. These compositions typically include an inert carrier and the active pharmaceutical ingredient, designed for various routes of administration (e.g., oral, topical). Methods of Treatment: The patent claims methods for treating inflammatory conditions. This involves administering a therapeutically effective amount of one of the claimed compounds to a patient in need thereof. What Was the Technological Context of This Patent? U.S. Patent 3,654,272 emerged during a period of significant advancement in understanding inflammation and pain pathways. Prostaglandin Inhibition The patent explicitly links the utility of its claimed compounds to the inhibition of prostaglandin synthesis. Prostaglandins are lipid compounds that play a crucial role in mediating inflammation, pain, and fever. At the time of the patent filing and grant, research into the biochemical mechanisms of inflammation was rapidly evolving. NSAID Development: The development of NSAIDs was a major focus of pharmaceutical research. Aspirin, a well-established anti-inflammatory and analgesic, was known to affect inflammatory processes, but the specific molecular targets were still being elucidated. Enzyme Targets: The patent aligns with the emerging understanding that certain enzymes, like cyclooxygenase (COX), are responsible for prostaglandin production. Compounds that could inhibit these enzymes were seen as potential therapeutic agents. Chemical Structure and Activity The steroid-like backbone of the claimed compounds is significant. Steroidal anti-inflammatory agents (e.g., corticosteroids) were already in use, but they had substantial side effects. The quest was for non-steroidal compounds that could achieve similar anti-inflammatory effects with a better safety profile. The specific modifications to the cyclopentanoperhydrophenanthrene ring system were designed to confer anti-inflammatory activity. What Is the Patent Landscape Surrounding U.S. Patent 3,654,272? As a patent granted in 1972, U.S. Patent 3,654,272 is long expired. Its term was 17 years from the date of grant, meaning it expired in 1989. However, understanding its place in the patent landscape involves considering its historical context and the subsequent developments in the field of NSAIDs. Preceding Patents Prior to 1972, numerous patents existed covering various chemical entities with potential therapeutic applications, including those with anti-inflammatory properties. Early NSAIDs like phenylbutazone and indomethacin were already known and patented. These earlier patents would have established the prior art for the chemical space that G.D. Searle & Company was attempting to patent. Subsequent Patent Activity The expiration of U.S. Patent 3,654,272 allowed for the generic manufacturing of any compounds that were exclusively covered by its claims, provided they were not covered by other, later-expiring patents. New Chemical Entities (NCEs): Pharmaceutical companies continued to develop new NSAIDs with improved efficacy, safety profiles, or different mechanisms of action. These NCEs were protected by new patents, often focusing on specific structural modifications or novel pharmacological properties. For example, the development of COX-2 selective inhibitors in the late 1990s and early 2000s represented a significant wave of patenting activity. Formulation Patents: Even after the expiration of composition-of-matter patents, companies could obtain patents on novel pharmaceutical formulations, dosage forms, or delivery systems for existing drugs. Method of Use Patents: Patents could be sought for new therapeutic uses of known compounds, even if the compound itself was off-patent. Impact on the Generic Market The expiration of U.S. Patent 3,654,272 would have theoretically opened the door for generic versions of the claimed compounds, assuming no other patents were in force that blocked such production. This is a standard trajectory for drug patents: an initial period of market exclusivity followed by the introduction of generic competition. What Are the Key Technical Aspects of the Claims? The technical strength and scope of a patent are derived from the specificity and breadth of its claims. Structural Definitions The core of claim 1 is the generic formula. The patent defines the "cyclopentanoperhydrophenanthrene ring system" as the fundamental scaffold. This refers to the fused ring structure characteristic of steroids. Substituents (R1 and R2): The defined options for R1 (hydrogen, methyl, ethyl) and R2 (hydroxyl, acetoxy, carboxyl) provide a degree of chemical diversity while still focusing on a specific class of modifications. Hydrogen: Simple presence or absence of a group. Methyl (CH3): A common alkyl group. Ethyl (C2H5): A slightly larger alkyl group. Hydroxyl (OH): An alcohol functional group. Acetoxy (OCOCH3): An ester derived from acetic acid. Carboxyl (COOH): An acidic functional group. 3-Position Substitution: The requirement for a hydroxyl, acetoxy, or carboxyl group at the 3-position further refines the structure and is critical for the asserted activity. Scope of the Claims The scope of the claims determines which specific compounds are protected. Broad Formula: Claim 1 is a generic claim, covering all compounds that fit the specified formula and substituent rules. This broad scope is a strength of the patent, as it encompasses multiple potential drug candidates. "Markush" Group: The use of "a member selected from the group consisting of..." defines Markush groups. These are common in chemical patents to claim a genus of compounds by defining a core structure and allowing for variations at specific positions. Specific Examples vs. Generic Claims: While generic claims provide broad protection, patents typically also include specific claims for individual compounds and their properties, which can sometimes be easier to enforce. What Is the Asserted Utility and How Is It Supported? The patent asserts that the claimed compounds are useful for treating inflammatory conditions through the inhibition of prostaglandin synthesis. Mechanism of Action Prostaglandin Inhibition: The patent describes the compounds as inhibitors of prostaglandin synthesis. This implies an interference with the enzymatic pathway responsible for producing prostaglandins, likely the cyclooxygenase (COX) pathway. Therapeutic Application: The primary therapeutic use identified is the treatment of inflammation. This could encompass a range of conditions characterized by swelling, redness, pain, and heat. Supporting Data Patents typically include experimental data to support the asserted utility. This data might include: In vitro assays: Tests demonstrating the ability of the compounds to inhibit prostaglandin production in cell cultures or enzyme preparations. In vivo studies: Animal model experiments showing the anti-inflammatory effects of the compounds in conditions like induced edema or arthritis. Dosage and Efficacy: Data indicating the effective dosage ranges for achieving the desired therapeutic effect. Safety/Toxicity: Preliminary data on the safety profile of the compounds, although this is often more extensively studied during drug development. What Are the Implications of U.S. Patent 3,654,272 for Today? Given its expired status, U.S. Patent 3,654,272 has direct implications for the historical understanding of the NSAID market rather than current commercial exclusivity. Historical Significance Foundational Research: This patent represents a specific point in the ongoing research and development of NSAIDs. It highlights the chemical approaches being taken to discover compounds that could modulate inflammatory pathways. Market Entry: The granting of this patent would have provided G.D. Searle & Company with a period of exclusivity to develop and market any drugs based on its claims. This exclusivity is crucial for recouping R&D investment. Precedent Setting: The patent’s claims and their structure contribute to the body of knowledge and patenting strategies in medicinal chemistry, particularly for steroid-like structures and anti-inflammatory agents. Impact on Generic Competition Freedom to Operate: With the patent expired, manufacturers of generic drugs are free to produce and sell compounds covered by its claims, provided no other active patents exist (e.g., patents on specific formulations, manufacturing processes, or new uses that are still in force). Market Pricing: The availability of generic versions typically leads to lower prices for medications, increasing patient access. Subsequent Innovation: The expiration of foundational patents often spurs further innovation. Companies may build upon the known structures and mechanisms to develop next-generation drugs with enhanced properties, protected by new patents. Conclusion U.S. Patent 3,654,272 is a historical document detailing a class of cyclopentanoperhydrophenanthrene derivatives claimed for their anti-inflammatory properties, linked to prostaglandin synthesis inhibition. Its claims define a specific chemical structure with variations at key positions. While the patent is expired, it marks a point in the evolution of NSAID development, influencing the subsequent landscape of pharmaceutical research, patenting, and generic market entry in this therapeutic area. Key Takeaways U.S. Patent 3,654,272, expired in 1989, covers novel cyclopentanoperhydrophenanthrene derivatives. The claimed compounds were asserted for their ability to treat inflammatory conditions by inhibiting prostaglandin synthesis. The patent's claims define a generic chemical structure with specific allowable substituents, offering broad protection for a class of molecules. The expiration of this patent enabled potential generic market entry for the claimed compounds, impacting pricing and accessibility. This patent is significant historically as a contribution to the development of NSAIDs and the patenting strategies within medicinal chemistry. Frequently Asked Questions What is the principal compound claimed in U.S. Patent 3,654,272? The patent claims a genus of compounds with a cyclopentanoperhydrophenanthrene core, characterized by specific substituents at defined positions. It does not claim a single "principal" compound but a class of related structures. Has this patent expired? Yes, U.S. Patent 3,654,272 was granted on April 4, 1972, and its term was 17 years, meaning it expired on April 4, 1989. Can generic versions of drugs based on this patent be manufactured today? Yes, compounds exclusively covered by U.S. Patent 3,654,272 can be manufactured as generics, provided no other valid patents (e.g., on specific formulations, manufacturing processes, or new uses) are still in force and block such production. What was the asserted mechanism of action for the claimed compounds? The patent asserts that the claimed compounds inhibit prostaglandin synthesis, which is linked to their utility in treating inflammatory conditions. Does this patent cover any currently marketed blockbuster drugs? Given the patent's expiration date of 1989, it is unlikely to cover any currently marketed drugs exclusively. Marketed drugs typically rely on patents granted much later or have multiple layers of patent protection that extend significantly beyond the term of older patents like 3,654,272. Cited Sources [1] U.S. Patent No. 3,654,272 (filed May 27, 1970) (issued Apr. 4, 1972). [2] U.S. Patent No. 3,654,272, Claim 1 (filed May 27, 1970) (issued Apr. 4, 1972). 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Details for Patent: 3,654,272

Summary for Patent: 3,654,272