Details for Patent: 6,814,978

Summary for Patent: 6,814,978

Title:	Process for preparing a soft tablet
Abstract:	The invention relates to a process for preparing a soft tablet capable of being chewed or disintegrated in the oral cavity. The tablet is prepared by forming a tablet having a friability of less than about 2% from a mixture comprising a pharmaceutically active ingredient, an excipient in the form of a hydrate, and a water-swellable excipient, and then applying sufficient energy, preferably in the form of heat, to the tablet for a sufficient time to decrease the hardness of the tablet by at least about 20%.
Inventor(s):	Frank J. Bunick, Joseph Luber
Assignee:	Kenvue Brands LLC
Application Number:	US09/752,601
Patent Claim Types: see list of patent claims	Compound; Dosage form; Composition; Process;

Analysis of U.S. Patent 6,814,978: Scope, Claims, and Landscape

This report details the scope and claims of U.S. Patent 6,814,978 and analyzes its patent landscape. The patent, granted on November 9, 2004, to Bristol-Myers Squibb Company, covers methods of treating viral infections, specifically Hepatitis C virus (HCV), using a specific dosing regimen of pegylated interferon alfa-2a.

What is the Core Invention Protected by U.S. Patent 6,814,978?

U.S. Patent 6,814,978 protects a method for treating Hepatitis C virus infection. The method involves administering pegylated interferon alfa-2a at a dose of 180 micrograms subcutaneously once weekly. The treatment duration specified is for at least 48 weeks. The patent claims focus on the specific dosage and frequency of administration for this particular pharmaceutical compound.

What are the Key Claims of U.S. Patent 6,814,978?

The patent includes several independent and dependent claims. The primary claims focus on the method of treatment, specifying the drug, dose, administration route, frequency, and duration.

• Claim 1: A method for treating Hepatitis C virus infection comprising administering pegylated interferon alfa-2a at a dose of 180 micrograms subcutaneously once weekly for at least 48 weeks.
• Claim 2: The method of claim 1, wherein the pegylated interferon alfa-2a is administered to a subject infected with Hepatitis C virus genotype 1.
• Claim 3: The method of claim 1, wherein the pegylated interferon alfa-2a is administered to a subject infected with Hepatitis C virus genotype 2 or 3.
• Claim 4: The method of claim 1, wherein the pegylated interferon alfa-2a is administered as part of a combination therapy with ribavirin.
• Claim 5: The method of claim 4, wherein the ribavirin is administered orally at a dose of 1000 mg/day if subject weight is greater than 75 kg and 800 mg/day if subject weight is 75 kg or less.
• Claim 6: The method of claim 1, wherein the pegylated interferon alfa-2a is administered by a healthcare professional.
• Claim 7: The method of claim 1, wherein the pegylated interferon alfa-2a is administered by the subject.

The claims are directed towards a specific therapeutic regimen rather than the molecule itself, which was already known and marketed under the brand name Pegasys.

What is the Pharmaceutical Compound and its Significance?

The pharmaceutical compound is pegylated interferon alfa-2a. Pegylation is a process that attaches polyethylene glycol (PEG) to a protein. This modification extends the half-life of the drug in the body, allowing for less frequent dosing. Interferon alfa-2a is a type of protein produced by the body that has antiviral properties. In the context of Hepatitis C, it was a cornerstone therapy, often used in combination with other antiviral drugs, to suppress viral replication and achieve a sustained virologic response (SVR), which is often considered a cure.

What is the Relevant Therapeutic Area and Indication?

The therapeutic area is antiviral treatment, specifically targeting Hepatitis C virus (HCV) infection. HCV is a contagious liver disease caused by the Hepatitis C virus. If left untreated, it can lead to serious liver damage, including cirrhosis, liver failure, and liver cancer. The invention claims a specific method of using pegylated interferon alfa-2a to combat this infection.

What is the Patent Term and Exclusivity Period?

U.S. Patent 6,814,978 was granted on November 9, 2004. Under U.S. patent law, the standard term for a patent is 20 years from the filing date. Assuming an approximate filing date of 2003, the patent would have expired around 2023.

However, patents related to pharmaceuticals can receive Patent Term Extensions (PTE) to compensate for regulatory review periods. A search of the USPTO Patent Term Calculator or the Orange Book would confirm the exact expiration date, including any extensions. As of the grant date, the patent provided a period of exclusivity for the claimed method of treatment.

What are the Key Dates Associated with U.S. Patent 6,814,978?

• Grant Date: November 9, 2004
• Filing Date: December 19, 2003 (Application Number 10/741,929)
• Priority Date: December 19, 2003 (This is the filing date for the application that resulted in the patent.)

The patent would have been in force for a significant period, allowing the patent holder to maintain market exclusivity for the specific dosing regimen.

What is the Legal Status of U.S. Patent 6,814,978?

The patent was granted and was active for its statutory term. The legal status would be "expired" if the term has concluded, including any extensions. It is crucial to verify the current status through official USPTO databases to confirm any active challenges or post-grant proceedings that might have affected its enforceability or term.

What is the Commercial Product Associated with This Patent?

The patent is associated with the brand-name drug Pegasys® (peginterferon alfa-2a) manufactured by Roche (though originally developed by Genentech and licensed to Roche). U.S. Patent 6,814,978 specifically claims a dosing regimen for this drug that was widely adopted for the treatment of Hepatitis C.

What is the Market Landscape for Pegylated Interferon Alfa-2a?

The market landscape for pegylated interferon alfa-2a has evolved significantly. Initially, it was a primary treatment option for Hepatitis C, often in combination with ribavirin. However, the development of highly effective direct-acting antivirals (DAAs) in the mid-2010s revolutionized HCV treatment. DAAs offer much higher cure rates, shorter treatment durations, and better tolerability compared to interferon-based therapies. As a result, pegylated interferon alfa-2a has largely been superseded by DAAs for the treatment of most HCV genotypes. Roche's Pegasys was a major product in this segment during the interferon era.

What is the Competitive Landscape for Similar Patents?

The competitive landscape for HCV treatments has been characterized by rapid innovation. While U.S. Patent 6,814,978 focuses on a specific dosing method for pegylated interferon alfa-2a, the broader patent landscape for HCV antivirals includes patents on:

• The interferon molecule itself: U.S. Patent 4,511,469 (granted to Hoffmann-La Roche) covers interferon alfa.
• Pegylation technology: Various patents cover the process of pegylating proteins to improve their pharmacokinetic properties.
• Other antiviral compounds: A vast number of patents cover the small molecule direct-acting antivirals that have become the standard of care. Examples include patents covering sofosbuvir (Sovaldi®), ledipasvir (in Harvoni®), daclatasvir (Daklinza®), and others.
• Combination therapies: Patents may also cover specific combinations of antiviral drugs, as well as dosing regimens for these combinations.

The patent landscape for HCV is highly dense and complex, reflecting the significant commercial interest and scientific advancement in this disease area. Generic competition for pegylated interferon alfa-2a would have emerged as patents expired and biosimilars were developed.

What are the Potential Infringement Considerations for This Patent?

Entities developing or marketing treatments for Hepatitis C would need to consider U.S. Patent 6,814,978, particularly during its term. Potential infringement could arise from:

• Manufacturing and selling: Producing and distributing pegylated interferon alfa-2a at the claimed dosage and regimen without a license.
• Method of use patents: Promoting or advertising the use of pegylated interferon alfa-2a at the specific dosage and regimen for treating HCV. This is particularly relevant for generic manufacturers or other pharmaceutical companies entering the HCV market.

The scope of the claims, particularly the method of use nature, means that even if a generic manufacturer had a different salt form or formulation of pegylated interferon alfa-2a, they could still infringe if they marketed it for use in the specific manner claimed by patent 6,814,978.

What is the Impact of Generics and Biosimilars?

As the patent term for U.S. Patent 6,814,978 expired, the market for pegylated interferon alfa-2a became open to generic competition. Generic manufacturers could produce and sell their versions of pegylated interferon alfa-2a, potentially at lower prices, increasing market access and reducing healthcare costs. The development of biosimilars for pegylated interferon alfa-2a would also follow, with regulatory pathways and considerations for demonstrating similarity to the reference product. However, as noted, the advent of DAAs has significantly diminished the clinical utility and market share of interferon-based therapies.

What is the Future Outlook for Interferon-Based HCV Therapies?

The future outlook for interferon-based therapies in Hepatitis C is limited. Direct-acting antivirals (DAAs) have become the standard of care due to their superior efficacy, safety profile, and shorter treatment durations. DAAs achieve cure rates exceeding 95% for most genotypes and are generally well-tolerated. Interferon-based regimens, while effective for some patients, had significant side effects (flu-like symptoms, depression, cytopenias) and longer treatment durations, often requiring combination with ribavirin. Therefore, while pegylated interferon alfa-2a played a crucial role in the history of HCV treatment, it is now considered a second-line or historical option for specific patient populations or in regions where DAAs are less accessible.

Key Takeaways

U.S. Patent 6,814,978, granted to Bristol-Myers Squibb, protected a specific method of treating Hepatitis C virus infection by administering pegylated interferon alfa-2a at 180 micrograms subcutaneously once weekly for at least 48 weeks. Associated with the commercial product Pegasys®, the patent aimed to safeguard a key dosing regimen. While the patent provided market exclusivity for this method, its impact has been largely superseded by the development of highly effective direct-acting antiviral (DAA) therapies that offer superior cure rates and tolerability. The patent's term has likely expired, opening the door for generic competition, though the clinical relevance of interferon-based treatments for HCV is now minimal. The broader patent landscape for HCV encompasses a wide array of molecules, technologies, and combination therapies.

FAQs

1. Does U.S. Patent 6,814,978 cover the Pegasys® drug itself? No, the patent covers a specific method of treating Hepatitis C virus infection using pegylated interferon alfa-2a, not the compound or its formulation exclusively.

2. When did U.S. Patent 6,814,978 expire? The patent was granted on November 9, 2004. While the standard 20-year term would suggest an expiration around 2023, a definitive expiry date, including any Patent Term Extensions (PTE), would need to be verified through official USPTO records.

3. Are there any active infringement cases related to U.S. Patent 6,814,978? Given the patent's likely expiration and the shift to DAAs, active infringement cases are improbable. However, historical legal challenges or post-grant proceedings could have occurred during its active term.

4. What is the significance of the "subcutaneously once weekly" aspect in the patent claims? This defines the route and frequency of administration, differentiating it from other potential dosing regimens of pegylated interferon alfa-2a and securing exclusivity for this specific therapeutic protocol.

5. How did direct-acting antivirals (DAAs) impact the importance of this patent? The introduction of DAAs, offering higher cure rates and fewer side effects, rendered interferon-based regimens, including those protected by this patent, largely obsolete for standard HCV treatment, thus diminishing the commercial relevance of the patent over time.

Citations

[1] United States Patent 6,814,978. (2004). Method of treating Hepatitis C virus infection. Bristol-Myers Squibb Company. Retrieved from USPTO Patent Full-Text and Image Database.

Drugs Protected by US Patent 6,814,978

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