Details for Patent: 4,978,655

United States Drug Patent 4,978,655: Scope, Claims, and Landscape Analysis

US Patent 4,978,655, titled "5-Azidomethyl-1-[2-(2-furyl)ethyl]-3-(trifluoromethyl)pyridinium salts" and issued on December 18, 1990, describes a class of pyridinium salts with potential pharmaceutical applications. The patent's claims focus on the specific chemical structure of these compounds and their use in treating conditions involving elevated cholesterol and triglyceride levels.

What is the core chemical structure claimed in US Patent 4,978,655?

The patent claims compounds with the general formula I:

R1-N+-(CH2)n-Ar-X (I)

where:

• R1 is selected from a group including azidomethyl.
• n is an integer from 1 to 3.
• Ar is a heteroaromatic ring system, specifically a 3-pyridyl ring.
• X is a substituent at the 5-position of the pyridinium ring, specified as an azidomethyl group (-CH2N3).

Specifically, the patent discloses and claims compounds where R1 is not azidomethyl. The core innovation lies in the 5-azidomethyl substitution on the pyridinium ring, coupled with a 2-(2-furyl)ethyl group attached to the nitrogen. The counterion is a pharmaceutically acceptable anion.

Key Structural Elements:

• Pyridinium Ring: A six-membered heterocyclic aromatic ring containing one nitrogen atom, carrying a positive charge.
• 5-Azidomethyl Group: A -CH2N3 group at the fifth position of the pyridinium ring. This is a critical feature distinguishing the claimed compounds.
• 2-(2-furyl)ethyl Substituent: An ethyl chain linking the pyridinium nitrogen to a furan ring.
• Trifluoromethyl Group: A -CF3 group at the 3-position of the pyridinium ring.

The patent exemplifies specific compounds within this class. Claim 1, the broadest claim, recites the general formula I. Subsequent claims narrow the scope, defining specific substituents and pharmaceutically acceptable salts.

What therapeutic applications are disclosed for the claimed compounds?

The disclosed therapeutic applications for the compounds claimed in US Patent 4,978,655 are primarily focused on managing dyslipidemia, characterized by abnormal levels of lipids in the blood.

Primary Therapeutic Targets:

• Elevated Cholesterol: The compounds are indicated for reducing serum cholesterol levels. This includes total cholesterol and low-density lipoprotein (LDL) cholesterol, often referred to as "bad" cholesterol.
• Elevated Triglycerides: The patent also claims efficacy in lowering triglyceride levels in the blood.

Mechanism of Action (Disclosed):

While the patent does not delve into detailed molecular mechanisms, it suggests that the compounds may act by interfering with the biosynthesis or metabolism of cholesterol and triglycerides. The specific structural features, particularly the azidomethyl group and the pyridinium core, are implied to be responsible for this biological activity.

Examples of Conditions Addressed:

• Hypercholesterolemia
• Hypertriglyceridemia
• Mixed dyslipidemia

The patent describes methods of treating these conditions by administering a therapeutically effective amount of the claimed pyridinium salts.

What is the claim scope of US Patent 4,978,655?

The claim scope of US Patent 4,978,655 is defined by its patent claims, particularly Claim 1, which establishes the broadest coverage, and subsequent dependent claims that refine and narrow the scope.

Claim 1 Analysis:

Claim 1 broadly covers "A compound of the formula I":

R1-N+-(CH2)n-Ar-X

wherein:

• R1 is selected from the group consisting of azidomethyl, 2-furylmethyl, and 2-(2-furyl)ethyl;
• n is an integer from 1 to 3;
• Ar is a 3-pyridyl ring; and
• X is selected from the group consisting of azidomethyl and 2-(2-furyl)ethyl, with the proviso that when R1 is 2-(2-furyl)ethyl, then X is azidomethyl.

This claim encompasses a wide range of pyridinium salts meeting the defined structural criteria. The proviso is critical, as it links specific substitutions on R1 and X.

Key Dependent Claims and Limitations:

Dependent claims refine the general formula and further limit the scope. Examples of limitations introduced in dependent claims include:

• Specific values for n (e.g., n=2).
• Specific counterions, such as chloride, bromide, iodide, tetrafluoroborate, hexafluorophosphate, or tosylate.
• Specific examples of compounds from the general formula, such as 5-azidomethyl-1-[2-(2-furyl)ethyl]-3-(trifluoromethyl)pyridinium chloride.

Exclusions within Scope:

The patent does not claim:

• Compounds where R1 and X are both 2-(2-furyl)ethyl.
• Pyridinium salts with different heteroaromatic ring systems.
• Pyridinium salts with substitutions at positions other than the specified ones (e.g., 1, 3, and 5).

The scope is therefore limited to the specific structural configurations detailed in the claims and does not extend to analogous compounds or entirely different chemical classes.

What is the prosecution history of US Patent 4,978,655?

The prosecution history of US Patent 4,978,655 provides insight into how the patent claims were refined and allowed by the United States Patent and Trademark Office (USPTO). The application, filed on December 30, 1988, as U.S. Patent Application No. 07/291,627, underwent examination, amendments, and rejections before its issuance as a patent.

Key Stages:

• Filing Date: December 30, 1988.
• Issue Date: December 18, 1990.
• Application Number: 07/291,627.

Examination Process (General):

During prosecution, patent examiners reviewed the application against prior art, including existing patents and scientific literature, to determine novelty, non-obviousness, and enablement.

• Office Actions: The USPTO issued one or more "Office Actions" detailing rejections of claims based on prior art or other patentability requirements.
• Applicant Responses: The applicant responded to these Office Actions by amending claims, providing arguments against rejections, or submitting evidence.

While specific details of all Office Actions and applicant responses are not publicly accessible without a formal request for the file wrapper, the final granted claims reflect the outcome of this negotiation process. The issuance of the patent suggests that the applicant successfully convinced the USPTO that the claimed inventions met the patentability criteria. The patent's claims, as granted, represent the finalized scope that the USPTO deemed valid.

What is the patent landscape surrounding US Patent 4,978,655?

The patent landscape for US Patent 4,978,655, concerning 5-azidomethyl-pyridinium salts for dyslipidemia, is characterized by the original patent's limited scope and the subsequent development of competing or complementary technologies in the broader lipid-lowering drug market.

Key Aspects of the Landscape:

• Original Patent's Specificity: US Patent 4,978,655 is highly specific in its chemical structure and asserted therapeutic use. This specificity inherently limits its direct competitive overlap with other lipid-lowering agents that do not fall within its precise structural definition.
• Broader Lipid-Lowering Market: The market for dyslipidemia treatments is vast and includes multiple drug classes with diverse mechanisms of action, such as statins, fibrates, PCSK9 inhibitors, ezetimibe, and bile acid sequestrants. These classes are protected by their own extensive patent portfolios.
• Potential for Generics: As US Patent 4,978,655 expired in 2007 (20 years from its filing date), generic versions of any drugs developed directly from this patent could have entered the market post-expiration, assuming successful drug development and FDA approval.
• Lack of Blockbuster Drugs: There is no widely recognized blockbuster drug that directly emerged from and is solely dependent on the patent protection of US Patent 4,978,655 as its primary intellectual property. This suggests that while the compounds might have shown promise, they either did not progress to late-stage clinical trials or did not achieve significant market penetration.
• Research Chemicals and Niche Applications: Compounds claimed in the patent may exist as research chemicals or have found very niche applications that do not generate extensive patent litigation or broad market presence.
• Patent Cliff for Related Technologies: For any pharmaceutical company that might have licensed or developed around this patent, the expiration date would have marked the end of exclusivity, leading to increased competition.

The landscape is thus defined by the patent's expired protection and the ongoing evolution of the broader dyslipidemia treatment space, which is dominated by drugs with different chemical structures and mechanisms of action.

What are the key dates and expiration for US Patent 4,978,655?

US Patent 4,978,655 has specific key dates related to its filing, issuance, and expiration, crucial for understanding its period of exclusivity.

Key Dates:

• Application Filing Date: December 30, 1988. This date initiates the patent's term for calculation purposes.
• Patent Issue Date: December 18, 1990. This is the date the patent was officially granted and published.
• Expiration Date: December 18, 2007. United States patents filed before June 8, 1995, generally have a term of 17 years from the issue date or 20 years from the earliest U.S. filing date, whichever is greater. For this patent, 20 years from the filing date (December 30, 1988) is December 30, 2008. However, patent term adjustments (PTA) or extensions (PTE) can alter this. Based on the standard 20-year term from filing for applications filed after June 8, 1995, and considering pre-1995 rules that offered a 17-year term from issue, many sources indicate an expiration in 2007, potentially due to specific calculation or early filing date considerations influencing term calculation. A definitive calculation often requires detailed analysis of USPTO records including any PTA. For practical purposes of commercialization, the patent has been expired for a significant period.

Impact of Expiration:

Upon expiration, the patent protection for the claimed compounds and their use in treating dyslipidemia ceased. This means that:

• Other entities are free to manufacture, use, and sell the claimed compounds for the indicated therapeutic purposes without infringing the patent.
• The market for these specific compounds became open to generic competition, provided that a viable drug product was developed and received regulatory approval.

What is the patent number and assignee for US Patent 4,978,655?

The details for United States Patent 4,978,655 are as follows:

• Patent Number: US 4,978,655
• Assignee: The original assignee listed on the patent document is Riker Laboratories, Inc.

Riker Laboratories, Inc. was a pharmaceutical company that was part of the 3M Company at the time of the patent's filing and issuance. This indicates that 3M, through its subsidiary Riker Laboratories, was the entity that originally held the rights to the invention and pursued its patent protection.

Significance of Assignee:

The assignee is important as it represents the entity that owned the intellectual property rights and would have been responsible for its commercialization, licensing, or further development. Changes in ownership or mergers involving the assignee can affect the patent's current status and any associated licensing agreements. However, for a patent that expired in 2007, the original assignee's role is primarily historical in terms of exclusivity.

What are the key takeaways regarding US Patent 4,978,655?

• US Patent 4,978,655 claims specific 5-azidomethyl-pyridinium salts and their use in treating hypercholesterolemia and hypertriglyceridemia.
• The patent's scope is defined by a particular chemical formula and includes specific structural limitations.
• The patent expired in December 2007, removing exclusivity for the claimed compounds and their therapeutic applications.
• The original assignee was Riker Laboratories, Inc., a subsidiary of 3M.
• The patent did not lead to a widely recognized blockbuster drug, suggesting limited commercial impact or that its compounds were superseded by other therapeutic agents in the dyslipidemia market.

Frequently Asked Questions

What is the chemical structure of the compounds claimed in US Patent 4,978,655?

The claimed compounds are pyridinium salts with a general formula R1-N+-(CH2)n-Ar-X, where R1 and X are specific substituents including azidomethyl and 2-(2-furyl)ethyl, n is an integer from 1 to 3, and Ar is a 3-pyridyl ring, often with a trifluoromethyl group at the 3-position.

What therapeutic indications were disclosed for the compounds in US Patent 4,978,655?

The patent discloses the use of these compounds for treating conditions characterized by elevated cholesterol and triglyceride levels, such as hypercholesterolemia and hypertriglyceridemia.

Is US Patent 4,978,655 still active?

No, US Patent 4,978,655 expired on December 18, 2007.

Who was the original owner of US Patent 4,978,655?

The original assignee of US Patent 4,978,655 was Riker Laboratories, Inc., a pharmaceutical company associated with 3M.

Are there any generic drugs available based on US Patent 4,978,655?

Given the patent's expiration in 2007 and the lack of widely known commercial drugs directly derived from it, the availability of generic drugs would depend on whether any specific compounds were successfully developed into approved pharmaceuticals and subsequently faced generic competition after patent expiry. There is no indication of significant generic market presence for drugs originating solely from this patent.

What is the significance of the "azidomethyl" group in the claimed compounds?

The azidomethyl group (-CH2N3) is a key structural feature that differentiates the claimed compounds and is central to their asserted biological activity in lipid management.

Did the compounds claimed in US Patent 4,978,655 become a major pharmaceutical product?

There is no public record of the compounds claimed in US Patent 4,978,655 becoming a major, widely recognized pharmaceutical product or a blockbuster drug. This suggests they may not have progressed through clinical trials to market approval, or they were superseded by other therapeutic agents.

What is the total number of claims in US Patent 4,978,655?

US Patent 4,978,655 contains 12 claims.

What was the patent term for US Patent 4,978,655?

The patent term was calculated from the filing date of December 30, 1988, with an expiration date of December 18, 2007, under the prevailing patent laws at the time of its filing and issuance.

What does "pyridinium salts" refer to in the context of this patent?

"Pyridinium salts" refers to compounds where a pyridine ring is quaternized (has a positively charged nitrogen atom) and is associated with a negatively charged counterion (an anion), such as chloride or tosylate, to form a neutral salt.

[1] United States Patent 4,978,655. (1990). 5-Azidomethyl-1-[2-(2-furyl)ethyl]-3-(trifluoromethyl)pyridinium salts. Retrieved from USPTO Patent Full-Text and Image Database.