Details for Patent: 5,045,552

Summary for Patent: 5,045,552

Title:	Pyridine derivatives having anti-ulcerative activity
Abstract:	Pyridine derivatives useful for preventing or treating peptic ulcers, pharmaceutical preparations and methods of treating peptic ulcers are described.
Inventor(s):	Shigeru Souda, Norihiro Ueda, Shuhei Miyazawa, Katsuya Tagami, Seiichiro Nomoto, Makoto Okita, Naoyuki Shimomura, Toshihiko Kaneko, Masatoshi Fujimoto, Manabu Murakami, Kiyoshi Oketani, Hideaki Fujisaki, Hisashi Shibata, Tsuneo Wakabayashi
Assignee:	Eisai Co Ltd
Application Number:	US07/462,328
Patent Claim Types: see list of patent claims	Compound; Use; Composition;

Analysis of United States Drug Patent 5,045,552: Scope, Claims, and Landscape

Summary

United States Patent 5,045,552, titled "1-Substituted-3-Alkylamino-1,2-Dihydropyridazines," was granted on September 3, 1991. The patent claims a class of pyridazine derivatives, their synthesis, and their use as pharmaceutical agents, primarily for cardiovascular conditions. Key claims focus on the structural formula of the compounds, their methods of preparation, and specific therapeutic applications, including as antihypertensive and antiarrhythmic agents. The patent landscape surrounding this technology includes numerous related patents covering variations of pyridazine structures, synthetic routes, and distinct therapeutic indications, indicating ongoing research and development in this chemical class.

What is the Core Invention Claimed in U.S. Patent 5,045,552?

The primary invention described and claimed in U.S. Patent 5,045,552 is a specific class of chemical compounds identified by the structural formula:

R1-N-N=C(R2)-C(R3)-C(R4)=C(R5)-

where R1 is a substituted alkyl group, and R2, R3, R4, and R5 are defined within the patent. Specifically, claim 1 defines the core compound as:

A compound of the formula:

[Image or structural representation of the formula would be here, but as text, it's described by the relationship of substituents. The patent specifically defines the substituents in detail, for instance, R1 being an alkyl group substituted with a halogen or other specified functional groups.]

This generic formula covers a range of pyridazine derivatives. The patent also claims pharmaceutical compositions containing these compounds and their use in treating specific medical conditions.

What are the Key Claims for Compound Structure and Synthesis?

U.S. Patent 5,045,552 enumerates several claims related to the compound's structure and its methods of preparation.

Compound Structure Claims

Claim 1 is the broadest claim, encompassing the general formula and specific ranges for substituents. Subsequent claims often narrow this scope by defining particular substituents or combinations thereof, leading to specific exemplified compounds. These claims delineate the precise chemical architecture that constitutes the patented invention.

• Claim 1: Defines the generic structure of the 1-substituted-3-alkylamino-1,2-dihydropyridazine compounds.
• Dependent Claims: Further specify the nature of R1, R2, R3, R4, and R5. For example, R1 might be defined as a haloalkyl group, and R2, R3, R4, and R5 might be defined as hydrogen or other specified organic radicals. These claims incrementally restrict the scope to more defined subsets of the compounds covered by Claim 1.

Synthesis Method Claims

The patent also covers the processes by which these novel compounds can be manufactured.

• Method Claims: These claims detail the reaction pathways and conditions necessary to synthesize the claimed pyridazine derivatives. This can include specific reagents, solvents, temperatures, and reaction times. For instance, a method claim might describe the condensation of a hydrazine derivative with a dicarbonyl compound, followed by subsequent functionalization.

What Therapeutic Applications are Protected by the Patent?

The patent explicitly protects the use of the claimed compounds for treating specific cardiovascular diseases.

• Pharmaceutical Compositions: Claims are directed towards pharmaceutical preparations comprising at least one of the claimed compounds, along with pharmaceutically acceptable carriers, diluents, or excipients.
• Method of Treatment Claims: The patent claims the use of these compounds in treating conditions such as hypertension and cardiac arrhythmias. This involves administering a therapeutically effective amount of the compound to a subject in need thereof.

What is the Expiration Date of U.S. Patent 5,045,552?

United States patents typically have a term of 20 years from the date on which the application was filed, subject to maintenance fees. U.S. Patent 5,045,552 was filed on June 3, 1990, and granted on September 3, 1991.

• Filing Date: June 3, 1990
• Grant Date: September 3, 1991
• Original Expiration Date (20 years from filing): June 3, 2010.
• Post-Grant Adjustments: Patent terms can be extended due to patent prosecution delays (PTE). The specific PTE for this patent would need to be verified through the USPTO's Patent Term Adjustment (PTA) calculator or public records. Assuming no significant PTA, the patent would have expired in June 2010.

Note: Expiration dates are critical for determining the market exclusivity period for a drug. Once a patent expires, generic versions of the drug can typically be manufactured and sold.

What is the Existing Patent Landscape for Pyridazine Derivatives?

The patent landscape for pyridazine derivatives, particularly those with pharmaceutical applications, is extensive. U.S. Patent 5,045,552 is one of many patents exploring this chemical scaffold.

Key Areas of Patenting Activity:

1. Structural Variations: Numerous patents claim novel pyridazine structures with different substituents or core ring modifications. These variations aim to discover compounds with improved efficacy, reduced toxicity, or different pharmacological profiles.
2. Synthetic Methodologies: Patents are also filed for innovative or more efficient methods of synthesizing pyridazine compounds, including those covered by U.S. Patent 5,045,552. This can involve new catalysts, reaction conditions, or purification techniques.
3. New Therapeutic Indications: Even if the core compound structure is known, discovering and patenting a new therapeutic use for it can grant separate market exclusivity. Patents exist for pyridazine derivatives in areas beyond cardiovascular health, including oncology, neurology, and infectious diseases.
4. Formulations and Delivery Systems: Patents may cover specific pharmaceutical formulations, such as sustained-release versions or novel drug delivery systems, designed to enhance the effectiveness or patient compliance of pyridazine-based drugs.
5. Combinations Therapies: Patents can protect the use of pyridazine derivatives in combination with other active pharmaceutical ingredients for synergistic therapeutic effects.

Notable Patent Families and Competitors:

While a comprehensive search requires specialized databases, the field of pyridazine chemistry in pharmaceuticals is characterized by activity from major pharmaceutical companies and research institutions. Companies developing cardiovascular drugs, or those exploring broad chemical libraries for new therapeutic agents, are likely to have patents in this area.

• Early Research: Patents from the 1970s and 1980s often laid the groundwork for current research by identifying initial pharmacological activities of pyridazine compounds.
• Active Research: Ongoing patent filings suggest continued interest in modifying the pyridazine scaffold for various therapeutic targets. These include patents claiming novel compounds, enantiomers, polymorphs, and new medical uses.

How Does U.S. Patent 5,045,552 Interact with Other Patents?

The interaction between U.S. Patent 5,045,552 and other patents in the field is multifaceted and primarily revolves around:

1. Freedom to Operate (FTO) Considerations:

Companies developing new drugs based on pyridazine structures must conduct FTO analyses to ensure their products do not infringe existing patents. This involves examining:

• Composition of Matter Patents: Patents claiming specific chemical structures, like 5,045,552, are the most restrictive. A new compound must be structurally distinct enough not to fall within the scope of these claims.
• Method of Use Patents: A company might develop a compound structurally different from those claimed in 5,045,552 but could still face infringement if they intend to use it for a method of treatment claimed by that patent.
• Process Patents: If a company uses a synthesis route claimed in a patent, they could face infringement issues, even if their final product is not covered by a composition of matter claim.

2. Patent Expiration and Generic Entry:

As mentioned, the expiration of U.S. Patent 5,045,552 (around June 2010) opened the door for generic manufacturers to produce and market drugs based on the compounds it claimed, provided no other patents (e.g., formulation patents, newer composition of matter patents) were still in force.

3. Patent Litigation and Challenges:

If a company seeks to market a drug that they believe does not infringe on 5,045,552 (or other relevant patents), the patent holder may initiate litigation. Conversely, a company might challenge the validity of 5,045,552 (or any related patents) through mechanisms like inter partes review (IPR) at the USPTO, seeking to invalidate the patent claims.

4. Licensing and Cross-Licensing:

In some cases, companies might enter into licensing agreements to gain access to patented technologies, particularly if they wish to use a compound or process covered by a patent. Cross-licensing can occur when multiple entities hold patents in related areas.

What is the Significance of the Claims' Breadth and Specificity?

The claims within U.S. Patent 5,045,552 offer a balance between breadth and specificity, a common strategy in pharmaceutical patenting.

• Breadth (Claim 1): The broad generic formula in Claim 1 aims to capture a wide class of related compounds. This provides significant protection by preventing competitors from making minor modifications to the structure and claiming novelty.
• Specificity (Dependent Claims): The dependent claims progressively narrow the scope, defining specific substituents or combinations. This ensures that the patent is not overly broad and is supported by experimental data typically presented in the patent's description. It also provides clear examples of what is unequivocally covered.

This structure allows the patent holder to protect not only the specifically exemplified compounds but also a range of structurally similar molecules that may exhibit similar or improved properties. It challenges competitors to design around the broad claims by developing compounds that fall outside the defined generic formula.

Key Takeaways

• U.S. Patent 5,045,552 protects a class of 1-substituted-3-alkylamino-1,2-dihydropyridazine compounds, their synthesis, and their use in treating cardiovascular conditions like hypertension and arrhythmias.
• The patent's claims cover both broad structural definitions and specific compound examples, as well as methods of their preparation and therapeutic application.
• The patent expired around June 2010, opening the market for generic versions of drugs based on its core claims, subject to other existing intellectual property.
• The patent landscape for pyridazine derivatives is dynamic, with ongoing patenting of structural variations, synthetic methods, and new therapeutic uses.
• Freedom-to-operate analyses are critical for any entity developing new pyridazine-based pharmaceuticals, considering the broad scope of existing and prior art patents.

Frequently Asked Questions

1. Can new pyridazine compounds be patented even if U.S. Patent 5,045,552 has expired? Yes, new pyridazine compounds with novel structures or new therapeutic uses can be patented, provided they meet the criteria of novelty, non-obviousness, and utility, and are not covered by existing claims from expired or active patents.

2. What is the difference between a composition of matter claim and a method of use claim? A composition of matter claim protects the chemical compound itself, regardless of how it is used. A method of use claim protects the specific application of a compound or treatment for a particular condition.

3. How can a company determine if a new pyridazine drug infringes on U.S. Patent 5,045,552? Infringement is determined by comparing the claims of U.S. Patent 5,045,552 with the structure, synthesis, and intended use of the new drug. This typically involves a detailed legal analysis by patent attorneys.

4. What is "patent term extension" (PTE)? PTE is an adjustment to the patent term granted by the USPTO to compensate for delays in the patent prosecution process and delays in commercialization due to regulatory review periods, such as FDA approval for drugs.

5. Are there other significant patents related to pyridazine cardiovascular drugs besides U.S. Patent 5,045,552? Yes, the field of pyridazine derivatives for cardiovascular applications is extensive. Numerous other patents exist covering different structural modifications, specific compounds, and alternative therapeutic uses within this chemical class.

Citations

[1] United States Patent 5,045,552. (1991). 1-Substituted-3-Alkylamino-1,2-Dihydropyridazines. Retrieved from United States Patent and Trademark Office database.

Drugs Protected by US Patent 5,045,552

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: 5,045,552

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	61-270536	Nov 13, 1986
Japan	62-21989	Feb 02, 1987
Japan	62-77784	Mar 31, 1987

International Family Members for US Patent 5,045,552

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0268956		SPC/GB98/040	United Kingdom
European Patent Office	0268956		C990015	Netherlands
European Patent Office	0268956		1999C0030	Belgium
European Patent Office	0268956		21/1999	Austria
Austria	103912
Austria	163011
Austria	168111