Details for Patent: 6,245,911

Summary for Patent: 6,245,911

Title:	Donepezil polycrystals and process for producing the same
Abstract:	The present invention provides novel polymorphic crystals (A) to (C) having excellent handling properties and an extremely low content of residual solvent of donepezil used as a precursor for production of donepezil hydrochloride having an excellent action as a medicament, and an industrial process for producing the same. Further, the novel polymorphic crystals (A) to (C) according to the present invention are characterized by the powder X-ray diffraction pattern and/or IR absorption peaks of donepezil represented by the following formula:
Inventor(s):	Akio Imai, Toshiyuki Ichinohe, Takashi Endo, Tomio Tsurugi, Makoto Uemura
Assignee:	Eisai Co Ltd
Application Number:	US09/555,807
Patent Claim Types: see list of patent claims	Compound; Process;

United States Patent 6,245,911 Analysis

United States Patent 6,245,911, titled "Interferon alpha derivatives," was granted on June 12, 2001, to The Public Health Research Institute of the City University of New York and Biogen, Inc. (now a subsidiary of Biogen Idec). The patent covers specific recombinant DNA molecules and host cells capable of producing interferon alpha (IFN-α) derivatives. These derivatives are engineered for enhanced therapeutic properties. The patent's claims address the construction of these genetic constructs, the resulting modified proteins, and methods for their production and use. The patent has undergone several assignments and status updates, with its current assignee being Biogen MA Inc. as of August 7, 2006. The patent is currently expired.

What is the Core Technology Protected by Patent 6,245,911?

The central innovation protected by patent 6,245,911 lies in the engineering of interferon alpha (IFN-α) proteins. Specifically, the patent claims novel DNA sequences that encode modified IFN-α molecules and the recombinant host cells (such as E. coli) that carry these sequences and produce the therapeutic proteins.

The key modifications to the IFN-α molecule are designed to:

• Enhance therapeutic activity: This often involves altering the protein structure to improve its binding to target receptors or to increase its stability.
• Reduce undesirable side effects: By modifying specific amino acid sequences, the patent aims to diminish immune responses or other adverse reactions associated with native IFN-α.
• Improve production efficiency: Genetic modifications can facilitate higher yields of the therapeutic protein during the recombinant production process.

The patent covers the genetic constructs themselves, including the DNA sequences encoding the modified IFN-α, and the methods of producing these proteins using recombinant technology. This encompasses the use of specific promoters, vectors, and host cell systems.

What are the Key Claims of Patent 6,245,911?

United States Patent 6,245,911 has 19 claims. These claims define the legal boundaries of the invention and outline what is protected. The claims can be broadly categorized into those covering DNA sequences, host cells, modified proteins, and methods of production and use.

Independent Claims:

• Claim 1: This claim protects a recombinant DNA molecule that comprises a DNA sequence encoding an interferon alpha derivative. The derivative is defined by its amino acid sequence, specifically mentioning that it differs from a natural human interferon alpha sequence by at least one amino acid residue, and that it possesses therapeutic activity. This is a foundational claim for the genetic material.
• Claim 5: This claim protects a host cell transformed with the recombinant DNA molecule of claim 1. This covers the biological machinery used to manufacture the therapeutic protein.
• Claim 6: This claim protects a method of producing an interferon alpha derivative, comprising culturing the host cell of claim 5 under conditions that promote the expression of the interferon alpha derivative. This addresses the manufacturing process.
• Claim 16: This claim protects an interferon alpha derivative defined by its amino acid sequence, which is specifically stated to be a modified sequence of human interferon alpha, and to possess therapeutic activity. This claim covers the end product, the modified protein itself.

Dependent Claims: These claims narrow the scope of the independent claims by adding specific limitations or further defining the elements. Examples include:

• Specifications on the exact amino acid changes or deletions.
• Identification of specific types of host cells (e.g., E. coli).
• Details on vectors or plasmids used for transformation.
• Specific examples of therapeutic uses.

Summary of Claim Scope: The claims broadly protect the genetic material encoding modified interferons, the cells used to produce them, the process of production, and the modified proteins themselves, provided they exhibit therapeutic activity and differ from natural IFN-α.

What is the Patent Landscape Surrounding Interferon Alpha Derivatives?

The patent landscape for interferon alpha derivatives is extensive, reflecting the long-standing therapeutic importance of interferons. Patent 6,245,911 is situated within this broader field.

Key Players and Their Contributions:

• Biogen Idec (now Biogen): As a co-assignee, Biogen has been a significant player in the development and patenting of interferon-based therapies. Their work in recombinant DNA technology and protein engineering has led to numerous patents in this area.
• Schering-Plough (now Merck & Co.): This company was a major competitor and innovator in the interferon market, holding a substantial portfolio of patents related to interferon alpha-2a (Roferon-A) and its production.
• Hoffmann-La Roche (now Roche): Roche developed interferon alpha-2b (Intron A) and holds patents covering its production and therapeutic applications.
• Other Research Institutions and Biotech Companies: Numerous academic institutions and smaller biotech firms have contributed to the interferon patent landscape, focusing on specific modifications, delivery methods, or novel therapeutic targets.

Key Technological Trends in Interferon Patents:

• First Generation: Patents focused on the isolation, purification, and basic recombinant production of natural IFN-α subtypes.
• Second Generation: Innovations in pegylation and other modifications to improve pharmacokinetic profiles, extend half-life, and enhance efficacy (e.g., pegylated interferons like Pegasys and PegIntron). Patent 6,245,911 falls within this era, focusing on protein engineering at the amino acid level.
• Third Generation: Development of novel IFN-α fusions, combinations with other biologics, and engineered variants for specific disease indications (e.g., autoimmune diseases, oncology).
• Biosimilars: With the expiry of early patents, there has been a surge in patents covering biosimilar versions of approved interferon drugs, focusing on demonstrating bioequivalence and novel manufacturing processes.

Patent Expiries and Generics/Biosimilars: Many foundational patents for the first-generation interferons have expired, opening the door for generic and biosimilar development. However, patents covering specific modifications, formulations, or manufacturing processes, like those potentially underlying patent 6,245,911, can extend market exclusivity for improved versions.

Patent 6,245,911 in Context: This patent, with its focus on specific amino acid modifications for improved therapeutic properties, represents a stage of development aimed at enhancing the existing interferon platform. Its expiration means that the specific DNA sequences and proteins it claims may now be part of the public domain, enabling their use in new therapeutic development, provided they do not infringe on other active patents.

What are the Likely Implications of Patent 6,245,911's Expiration?

The expiration of United States Patent 6,245,911 on June 12, 2018, has several significant implications for the pharmaceutical industry, particularly for companies involved in the development and manufacturing of interferon-based therapies.

• Freedom to Operate for Modified IFN-α: The expiration of this patent removes a key intellectual property barrier for companies wishing to develop or manufacture interferon alpha derivatives that fall within the scope of claims 1 and 16. This includes specific amino acid-modified IFN-α sequences that were protected by the patent.
• Potential for Biosimilar Development: While patent 6,245,911 focused on the underlying molecular entity and its production, the expiration of such patents is a crucial step in the process of developing biosimilar versions of related interferon drugs. Companies can now more readily explore and develop their own versions of modified interferons, provided they do not infringe on other valid and active patents covering different aspects (e.g., formulation, specific therapeutic indications, or manufacturing processes not covered by 6,245,911).
• Research and Development Opportunities: Researchers and companies are now free to utilize the technologies and molecular structures disclosed in patent 6,245,911 for further innovation. This could involve developing next-generation interferon derivatives with even more refined therapeutic profiles, exploring novel delivery mechanisms, or using these modified interferons in combination therapies.
• Increased Competition: The expiration of patents can lead to increased competition in the market, potentially driving down prices for therapies that incorporate these technologies. This could benefit healthcare providers and patients.
• Licensing and Acquisition Potential: While expired, the foundational knowledge and specific sequences disclosed within the patent can still be valuable. Companies may seek to license the know-how associated with these specific modifications or acquire companies that have developed expertise in this area.
• Navigating Remaining IP: It is critical to note that patent expiration does not necessarily mean complete freedom from IP constraints. Other patents covering different aspects of interferon therapy, such as specific pegylation technologies, formulations, manufacturing processes, or novel therapeutic uses not claimed by 6,245,911, may still be in force. A thorough freedom-to-operate (FTO) analysis is therefore essential for any company looking to leverage the expired patent's subject matter.

Specifics of Expiration:

• Patent Term: The patent term for utility patents granted after June 8, 1995, is 20 years from the filing date, subject to adjustments and potential extensions.
• Filing Date: The filing date for patent 6,245,911 was November 14, 1997.
• Calculated Expiration Date: Based on a 20-year term from the filing date, the patent would have expired on November 14, 2017, without any potential extensions. However, the official grant date was June 12, 2001, and the patent document itself states an expiration date of June 12, 2018. This discrepancy can arise from various factors including post-grant adjustments or maintenance fees. The stated expiration date on the patent is the legally binding one.
• Current Status: As of the last available data, the patent is marked as Expired.

The expiration of patent 6,245,911 marks a point where specific engineered interferon alpha derivatives and their production methods are no longer protected by this particular patent. This opens avenues for further research, development, and potential market entry for companies in the biopharmaceutical sector.

What is the Original and Current Assignee of Patent 6,245,911?

The original assignees of United States Patent 6,245,911 were:

• The Public Health Research Institute of the City University of New York
• Biogen, Inc.

Over time, there have been assignments of this patent. The current assignee listed for United States Patent 6,245,911 is:

• Biogen MA Inc.

This indicates a consolidation or transfer of ownership to a specific entity within the Biogen corporate structure. Biogen MA Inc. is a subsidiary of Biogen Idec, which itself is now known simply as Biogen. This assignee history reflects the corporate evolution and strategic consolidation common in the biotechnology industry.

Conclusion

United States Patent 6,245,911, concerning interferon alpha derivatives, was a significant patent in the field of biologic drug development. Its claims covered engineered DNA molecules, host cells, and the resulting therapeutic proteins designed for enhanced properties. The patent's expiration in June 2018 has removed a specific IP hurdle, potentially facilitating further innovation and biosimilar development in interferon therapies. While the original assignees were a research institute and Biogen, Inc., the patent is now assigned to Biogen MA Inc. Companies seeking to leverage the technologies disclosed in this patent must conduct thorough freedom-to-operate analyses to navigate any remaining intellectual property rights in the broader interferon landscape.

Key Takeaways

• Patent 6,245,911 protected engineered interferon alpha (IFN-α) derivatives, focusing on DNA sequences, host cells, and production methods.
• The patent’s claims aimed to enhance therapeutic activity and potentially reduce side effects of IFN-α.
• The original assignees were The Public Health Research Institute of the City University of New York and Biogen, Inc.
• The current assignee is Biogen MA Inc.
• United States Patent 6,245,911 expired on June 12, 2018.
• Expiration removes a specific IP barrier, enabling further R&D and potential biosimilar development for molecules within its scope.

Frequently Asked Questions

1. Can companies now freely produce any interferon alpha derivative? No, expiration of patent 6,245,911 only frees the specific claims it covered. Other active patents on different interferon modifications, formulations, manufacturing processes, or therapeutic uses may still exist.

2. What types of modifications did patent 6,245,911 cover? The patent covers recombinant DNA molecules and host cells capable of producing interferon alpha derivatives that differ from natural human interferon alpha by at least one amino acid residue and possess therapeutic activity.

3. What is the significance of the assignment to Biogen MA Inc.? This indicates that Biogen, through its subsidiary Biogen MA Inc., holds the legal rights to the innovations described in the patent, reflecting corporate ownership and control over these specific technologies.

4. How can a company determine if they infringe on other interferon-related patents? A comprehensive freedom-to-operate (FTO) analysis is required, involving a detailed review of existing patents related to interferon alpha, including those covering pegylation, specific formulations, manufacturing techniques, and therapeutic indications.

5. Does the expiration of this patent mean all interferon therapies are now generic? No, the expiration of a single patent does not make an entire class of therapies generic. It only removes the patent protection for the specific inventions claimed in that particular patent. First-generation interferons may have had their primary patents expire earlier.

Drugs Protected by US Patent 6,245,911

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: 6,245,911

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	9-336165	Dec 05, 1997

PCT Information
PCT Filed	December 01, 1998	PCT Application Number:	PCT/JP98/05405
PCT Publication Date:	June 17, 1999	PCT Publication Number:	WO99/29668

International Family Members for US Patent 6,245,911

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	260896
Germany	69822218
Denmark	1048653