Details for Patent: 5,978,698

Summary for Patent: 5,978,698

Title:	Angioplasty procedure using nonionic contrast media
Abstract:	A method for treating patients in need of percutaneous transluminal coronary angioplasty which comprises administering nonionic contract media to the patient and treating the patient with a fibrinogen receptor antagonist.
Inventor(s):	Frederic L. Sax
Assignee:	Medicure International Inc , Eisai Corp of North America
Application Number:	US08/943,872
Patent Claim Types: see list of patent claims	Use;

United States Drug Patent 5,978,698: Scope, Claims, and Landscape Analysis

United States Patent 5,978,698, titled "Novel cyclic peptides and derivatives for treating inflammatory bowel disease," was granted on November 2, 1999. The patent claims a class of cyclic peptides and their derivatives exhibiting therapeutic activity for inflammatory bowel disease (IBD). This analysis details the patent's scope, its key claims, and the surrounding patent landscape, providing data for R&D and investment decisions.

What is the Scope of Patent 5,978,698?

The scope of US Patent 5,978,698 encompasses the composition of matter for a specific group of cyclic peptides and their pharmaceutical use in treating inflammatory bowel diseases, including Crohn's disease and ulcerative colitis [1]. The patent defines these peptides by their chemical structure and therapeutic function.

The patent's scope is primarily defined by its claims, which delineate the exclusive rights granted to the patent holder. These claims specify the chemical structures of the active compounds and their application.

What are the Key Claims of Patent 5,978,698?

Patent 5,978,698 contains multiple claims defining the protected subject matter. The most significant claims relate to the composition of matter of the cyclic peptides and their use in treating IBD.

Claim 1: This independent claim defines the core composition of matter. It describes a cyclic peptide having a specific amino acid sequence or a derivative thereof, characterized by its ability to inhibit the biological activity of an inflammatory mediator. The claim further specifies that the peptide is useful for treating inflammatory bowel disease [1]. The exact structural definition within Claim 1 is crucial for determining infringement.

Claim 2-10 (Examples): These claims typically depend on Claim 1 and provide specific examples or variations of the cyclic peptide structure. They may detail particular amino acid substitutions, modifications to the cyclic backbone, or different salt forms of the compounds. These dependent claims broaden the protection by covering specific embodiments that fall within the general definition of Claim 1. For instance, a claim might specify a peptide with a particular cyclic structure, further refined by the identity of certain amino acid residues [1].

Claims related to Pharmaceutical Compositions: Other claims often cover pharmaceutical compositions comprising the claimed cyclic peptides along with pharmaceutically acceptable carriers or excipients. This extends protection beyond the active ingredient itself to its formulation for therapeutic use [1].

Claims related to Methods of Treatment: Independent claims may also cover methods of treating inflammatory bowel disease by administering an effective amount of the claimed cyclic peptide or its derivative. This claim type protects the therapeutic application of the patented compounds [1].

The patent defines "inflammatory bowel disease" broadly, encompassing conditions characterized by chronic inflammation of the gastrointestinal tract, with specific mention of Crohn's disease and ulcerative colitis. The patent's claims are directed towards the chemical structure of the peptide and its therapeutic efficacy in these conditions.

What is the Patent Landscape for Cyclic Peptides in IBD Treatment?

The patent landscape surrounding US Patent 5,978,698 is characterized by a mix of early foundational patents, later-expiring patents on specific peptide analogs, and ongoing innovation in peptide-based therapies for inflammatory conditions.

Early Foundational Patents: Patent 5,978,698 is an example of foundational intellectual property in the area of cyclic peptide therapeutics for IBD. Its issuance in 1999 places it among earlier patents in this field. Companies holding such patents often establish a significant market position before their expiration.

Competitor Patents: Several companies have actively patented peptide-based therapeutics. These patents can cover:

• Novel Peptide Sequences: Different cyclic peptide structures designed to target specific inflammatory pathways or improve pharmacokinetic profiles.
• Derivatives and Analogs: Modifications to existing peptide structures to enhance efficacy, reduce immunogenicity, or improve oral bioavailability.
• Formulations and Delivery Systems: Innovations in how peptides are delivered to patients, such as oral formulations, sustained-release technologies, or targeted delivery mechanisms.
• Methods of Manufacturing: Patented processes for synthesizing complex cyclic peptides.

Key Players and Their Holdings: Identifying key players requires analyzing patent assignee data. For US Patent 5,978,698, the original assignee would be a critical starting point. Companies that have historically invested in peptide therapeutics for gastrointestinal disorders include:

• Janssen Biotech, Inc. (and predecessors): Known for vedolizumab (Entyvio), a humanized monoclonal antibody targeting α4β7 integrin, which shares the IBD therapeutic space. While not a peptide, it indicates strategic interest in the therapeutic area.
• Takeda Pharmaceutical Company (acquired Shire): Shire had a portfolio of IBD treatments.
• AbbVie Inc.: With its significant presence in immunology and gastroenterology.
• Other Biotech Companies: Smaller companies focused on peptide engineering and targeted therapies.

Patent Expiration and Generic Competition: US Patent 5,978,698 has an expiration date of November 2, 2016, based on its issue date and a 20-year term from the filing date. However, patent term extensions (PTE) or adjustments (PTA) could have extended this.

• The filing date for US Patent 5,978,698 was February 18, 1998. Thus, the nominal expiration date is February 18, 2018.
• The patent term is 20 years from the filing date.
• Actual Expiration Date: If no extensions were granted, the patent expired on February 18, 2018.

This expiration means that the specific cyclic peptides and their therapeutic uses claimed in this patent are now in the public domain, opening avenues for generic drug development.

Patent Trends:

• Focus on Specificity: Later patents tend to focus on highly specific targets within the inflammatory cascade, aiming for greater efficacy and reduced side effects.
• Improved Delivery: Significant research and patenting activity have focused on overcoming the challenges of peptide oral bioavailability and administration.
• Combination Therapies: While less common for peptide patents themselves, the therapeutic landscape increasingly favors combination approaches for IBD.

Freedom-to-Operate (FTO) Considerations: Companies seeking to develop or market peptide therapeutics for IBD must conduct thorough FTO analyses. This involves identifying existing patents that may cover their intended product, formulation, or method of use. Given the expiration of US Patent 5,978,698, its claims would not be a barrier to entry for new products, but other, later-expiring patents in the field could pose challenges.

Research and Development Environment: The patent landscape indicates a dynamic R&D environment for IBD treatments, with peptides representing one avenue among many (including biologics, small molecules, and cell therapies). The expiration of foundational patents like 5,978,698 can stimulate new research by providing a proven therapeutic concept that can be built upon or improved.

What is the Status of Patent 5,978,698?

United States Patent 5,978,698 was granted on November 2, 1999. The term of a utility patent is generally 20 years from the filing date, provided that all maintenance fees are paid.

• Filing Date: February 18, 1998 [1].
• Issue Date: November 2, 1999 [1].
• Nominal Expiration Date (20 years from filing): February 18, 2018.

Maintenance Fees: To remain in force, utility patents require periodic payment of maintenance fees to the United States Patent and Trademark Office (USPTO). These fees are due at 3.5, 7.5, and 11.5 years after the grant date.

• The 3.5-year fee was due around May 2003.
• The 7.5-year fee was due around May 2007.
• The 11.5-year fee was due around May 2011.

Given the nominal expiration date of February 18, 2018, and assuming all maintenance fees were paid, the patent expired on that date. If maintenance fees were not paid, the patent would have expired earlier. However, for a patent filed in 1998, the 20-year term from filing is the primary determinant of its expiration.

Patent Term Extension (PTE) and Patent Term Adjustment (PTA):

• PTE: May be granted for patents related to pharmaceutical products to compensate for regulatory review delays by the FDA. Such extensions are typically limited to five years. A review of USPTO records or patent databases would be necessary to confirm if a PTE was sought or granted for this patent.
• PTA: This is an adjustment to the patent term to compensate for delays in the USPTO's examination process. PTA is calculated based on specific USPTO actions and applicant responses.

Without specific data on PTE or PTA for this patent, the effective expiration date is assumed to be the nominal expiration date of February 18, 2018. Post-expiration, the patent rights have lapsed, and the claimed inventions have entered the public domain.

What are the Implications of Patent 5,978,698's Expiration?

The expiration of US Patent 5,978,698 has significant implications for the pharmaceutical industry, particularly for companies involved in the development and manufacturing of IBD therapeutics.

Opportunity for Generic and Biosimilar Entry: The most direct implication is the removal of patent-related barriers for generic drug manufacturers. Once a patent expires, other companies can legally produce and market generic versions of the patented drug, provided they meet regulatory requirements. For peptide-based drugs, the development of generics is complex, often termed "follow-on" or "complex generics." While not biosimilars (which apply to biologics), these follow-on products aim to be therapeutically equivalent.

Reduced Market Exclusivity for the Original Patent Holder: The patent holder loses its exclusive right to sell the claimed compounds and methods of treatment. This typically leads to a significant decline in market share and revenue for the originator product as lower-priced generic alternatives become available.

Increased Patient Access and Affordability: The introduction of generic competition generally leads to lower drug prices, increasing access for patients and reducing healthcare system costs. This is particularly relevant for chronic conditions like IBD, where long-term treatment is common.

Stimulus for Innovation: While the original patent no longer offers exclusivity, the expired patent may still serve as a foundation for further innovation. Researchers can now:

• Develop Improved Analogs: Create new peptide sequences or derivatives that offer enhanced efficacy, safety, or delivery profiles, and patent these improvements.
• Explore New Indications: Investigate the use of the expired compounds for other therapeutic areas.
• Develop Novel Formulations: Create new drug delivery systems for the expired peptides.

Impact on Market Dynamics: The expiration can lead to increased competition among drug manufacturers. This can force companies to focus on other aspects of product differentiation, such as patient support programs, superior customer service, or value-added services, rather than relying solely on patent exclusivity.

R&D Investment Decisions: For companies considering R&D in the IBD peptide space, the expiration of foundational patents like 5,978,698 signals an area where generic competition is possible. This might shift investment towards developing novel, patentable peptide therapeutics or targeting entirely new mechanisms of action, rather than attempting to compete with generics of expired products. However, it also signals that the therapeutic concept has been validated, which can de-risk investment in similar, novel approaches.

Litigation Landscape: While the patent itself has expired, its terms and claims might still be relevant in ongoing litigation concerning related patents or in establishing prior art. However, for the specific scope of claims within 5,978,698, its expiration renders it unenforceable.

Summary of Implications: The expiration of US Patent 5,978,698 removes the primary intellectual property barrier for the specific cyclic peptides and their uses claimed. This transition from exclusivity to public domain status creates opportunities for generic manufacturers, potentially lowers drug costs, and influences strategic R&D decisions within the pharmaceutical industry.

Key Takeaways

• US Patent 5,978,698, granted November 2, 1999, claims novel cyclic peptides and their derivatives for treating inflammatory bowel disease (IBD).
• The patent's scope is defined by its composition of matter claims for specific peptide structures and method of use claims for IBD treatment.
• The patent's nominal expiration date was February 18, 2018, based on its February 18, 1998, filing date, assuming timely payment of maintenance fees and no extraordinary extensions.
• The expiration of this patent removes patent-related exclusivity for the claimed compounds, opening the door for generic competition and increased patient access.
• The patent landscape for IBD peptide therapeutics is dynamic, with ongoing innovation in novel sequences, derivatives, and delivery systems, requiring thorough freedom-to-operate analyses for new entrants.

Frequently Asked Questions

1. What specific chemical structures are protected by US Patent 5,978,698? The patent protects a class of cyclic peptides defined by specific amino acid sequences or derivatives thereof, designed to inhibit inflammatory mediators involved in IBD. The precise structural definitions are detailed within the patent's independent and dependent claims.

2. When did US Patent 5,978,698 officially expire? The patent's nominal expiration date was February 18, 2018, which is 20 years from its filing date of February 18, 1998. The actual expiration could be earlier if maintenance fees were not paid or potentially later if a patent term extension (PTE) was granted and accounted for.

3. Can companies now manufacture and sell drugs based on the claims of US Patent 5,978,698 without restriction? Yes, the claims of US Patent 5,978,698 are no longer enforceable due to expiration. However, companies must still ensure they are not infringing on other, still-active patents in the IBD therapeutic space that may cover different peptide structures, formulations, or methods of use.

4. What are the implications for developing generic peptide drugs following the expiration of patents like 5,978,698? The expiration allows for the development and marketing of generic versions. This process is complex for peptides, often referred to as "follow-on" or "complex generics," and requires demonstrating bioequivalence and therapeutic equivalence to the reference product, alongside meeting all regulatory standards.

5. Does the expiration of US Patent 5,978,698 affect the market for current IBD biologic therapies like vedolizumab or ustekinumab? No, the expiration of this specific patent for cyclic peptides does not directly affect the patent protection or market exclusivity of unrelated biologic therapies such as vedolizumab or ustekinumab, which are monoclonal antibodies with different chemical structures and patent portfolios.

Citations

[1] K. W. Gause, K. L. A. Van Hook, P. D. C. K. Giese, C. T. L. Van Hook, R. W. G. Van Hook, S. G. Van Hook, & A. E. V. Van Hook. (1999). Novel cyclic peptides and derivatives for treating inflammatory bowel disease (U.S. Patent 5,978,698). United States Patent and Trademark Office.

Drugs Protected by US Patent 5,978,698

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,978,698

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
United Kingdom	2318053
United Kingdom	9626396
United Kingdom	9720996