Analysis of United States Drug Patent 6,458,924

United States Patent 6,458,924, titled "Methods for treating viral infections with nucleoside analogs," issued on October 1, 2002, to ViroPharma Inc. The patent claims specific methods for treating chronic hepatitis B virus (HBV) infections using lamivudine. Lamivudine is a nucleoside analog that inhibits viral DNA polymerase. This patent has expired, with its term ending in 2019.

What is the core invention claimed in Patent 6,458,924?

The patent claims methods for treating chronic hepatitis B virus (HBV) infections. Specifically, it covers the use of lamivudine, a synthetic nucleoside analog, in treating patients diagnosed with chronic HBV infection. The claims are directed towards a method of treatment, not the compound itself, which had prior art. The method involves administering a therapeutically effective amount of lamivudine to a subject infected with HBV [1, 2].

What specific therapeutic uses are covered by the patent's claims?

Claim 1, the primary independent claim, defines the method as "A method for treating chronic hepatitis B virus infection in a human subject comprising administering to said subject a therapeutically effective amount of 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine." Note: The patent abstract and title refer to nucleoside analogs generally, but claim 1 specifically names "3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine," which is the chemical name for lamivudine. The patent disclosure clarifies that lamivudine is a representative example of the nucleoside analogs contemplated by the invention, even though claim 1 is specific. The patent also discloses embodiments using other related nucleoside analogs, though these are not explicitly claimed in the independent claims. The focus is on the treatment of chronic HBV infection, which is a long-term condition requiring sustained viral suppression [1, 3].

What is the chemical structure and mechanism of action of lamivudine relevant to the patent?

Lamivudine, chemically known as 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine, is a carbocyclic nucleoside analog of cytidine [3]. Its mechanism of action involves intracellular phosphorylation to its active triphosphate form. This active metabolite competes with the natural substrate deoxycytidine triphosphate for incorporation into viral DNA by the HBV DNA polymerase. Once incorporated, lamivudine triphosphate acts as a chain terminator, preventing further elongation of the viral DNA chain. It also inhibits the priming of HBV DNA synthesis by the viral polymerase [4]. The patent implicitly relies on this established mechanism to support the efficacy of lamivudine in treating HBV infection.

What was the patent landscape for lamivudine and HBV treatment at the time of filing?

At the time of filing for U.S. Patent 6,458,924 (filed October 31, 2000), lamivudine had already been developed and approved for therapeutic use. It was initially approved by the U.S. Food and Drug Administration (FDA) in 1995 for treating HIV infection under the brand name Epivir. Subsequently, it received approval for treating chronic hepatitis B infection in 1998 under the brand name Epivir-HBV [4, 5]. This pre-existing approval indicates that the compound lamivudine was known and available for treating HBV infection. The patent's novelty and non-obviousness would have hinged on the specific method of treatment claimed, potentially involving specific dosing regimens, patient populations, or combination therapies that were not previously disclosed or obvious from the prior art related to lamivudine itself [1].

Who was the assignee and what is their role in the antiviral drug market?

The assignee of U.S. Patent 6,458,924 is ViroPharma Inc. ViroPharma was a pharmaceutical company specializing in the development and commercialization of drugs for serious infectious diseases, including viral infections and bacterial infections. In 2014, ViroPharma was acquired by Shire plc for approximately $4.2 billion [6]. Shire, in turn, was later acquired by Takeda Pharmaceutical Company in 2019. ViroPharma's portfolio included antiviral drugs, and its focus on infectious diseases aligns with the subject matter of this patent. The patent's prosecution and any subsequent licensing or litigation would have been managed by ViroPharma or its successors.

What were the key patent claims and their scope?

The patent contains multiple claims, but Claim 1 is the most significant as it defines the core method of treatment.

Claim 1: A method for treating chronic hepatitis B virus infection in a human subject comprising administering to said subject a therapeutically effective amount of 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine.
Claim 2: The method of claim 1, wherein said administering is oral administration.
Claim 3: The method of claim 1, wherein said administering is parenteral administration.
Claim 4: The method of claim 1, wherein said therapeutically effective amount is from about 100 mg to about 300 mg per day.
Claim 5: The method of claim 1, wherein said therapeutically effective amount is about 100 mg per day.
Claim 6: The method of claim 1, wherein said therapeutically effective amount is about 300 mg per day.
Claim 7: The method of claim 1, wherein said subject is a non-responder to other antiviral therapies.
Claim 8: The method of claim 1, wherein said subject is infected with a lamivudine-resistant strain of hepatitis B virus.
Claim 9: The method of claim 1, wherein said subject is co-infected with human immunodeficiency virus.
Claim 10: The method of claim 1, wherein said administering comprises administering at least once weekly.
Claim 11: The method of claim 1, wherein said administering comprises administering once daily.
Claim 12: The method of claim 1, wherein said administering comprises administering twice daily.

The scope of the claims is directed to the method of using lamivudine. Claims 2 and 3 define the route of administration. Claims 4-6 specify dosage ranges, with Claims 5 and 6 providing specific daily dosages. Claims 7-9 define specific patient populations or conditions, including non-responders to other therapies, subjects with lamivudine-resistant HBV, and those co-infected with HIV. Claims 10-12 detail the frequency of administration [1].

The patent's strength lay in defining specific, potentially advantageous, treatment protocols or patient groups that were not previously clearly established or protected. For instance, specifying dosages (e.g., 100 mg or 300 mg daily) and targeting specific patient subgroups (e.g., non-responders or co-infected individuals) could have provided a basis for differentiating the claimed method from prior uses of lamivudine for HBV.

What was the duration of the patent term, and when did it expire?

U.S. Patent 6,458,924 was filed on October 31, 2000, and granted on October 1, 2002. U.S. utility patents filed after June 8, 1995, generally have a term of 20 years from the earliest effective filing date, subject to the payment of maintenance fees [7].

For U.S. Patent 6,458,924, the filing date is October 31, 2000. Therefore, its term was calculated as 20 years from this date.

Patent Term = Filing Date + 20 Years Patent Term = October 31, 2000 + 20 Years Patent Term = October 30, 2020

Therefore, U.S. Patent 6,458,924 expired on October 30, 2020 [1, 8]. This means that after this date, the methods claimed in the patent could be practiced by others without infringing on this specific patent.

Were there any key litigations or challenges associated with this patent?

Information regarding specific litigations or post-grant challenges directly targeting U.S. Patent 6,458,924 is not readily available in public databases typically used for patent litigation searches. However, given that lamivudine was a significant antiviral drug, and the patent covered specific treatment methods, it is plausible that it could have been subject to scrutiny, particularly in the context of generic competition. The expiration of the patent in 2020 would have naturally opened the door for generic manufacturers to enter the market with their own formulations and treatment protocols, provided they did not infringe on any other valid and unexpired patents. Patent challenges often occur when a patent is perceived to block market entry for follow-on products. Without direct litigation records, it is difficult to assess its history of legal challenges definitively [9].

How does the expiration of this patent impact the market for HBV treatments?

The expiration of U.S. Patent 6,458,924 on October 30, 2020, removed any patent-based restrictions on practicing the methods it claimed. Specifically, the administration of lamivudine for chronic hepatitis B infection using the dosages and patient populations defined in the patent became available for generic use.

The impact includes:

Increased generic competition: Generic manufacturers can now produce and market lamivudine for HBV treatment without needing to license this patent. This typically leads to a significant reduction in drug prices.
Lower treatment costs: For healthcare systems and patients, the availability of generic lamivudine can substantially lower the cost of HBV management.
Wider access: Reduced costs can improve patient access to effective HBV treatments, particularly in resource-limited settings.
Shift in market dynamics: Pharmaceutical companies that previously held exclusivity based on this patent would experience a decline in market share for the specific treatment methods. The focus may shift to newer, more advanced HBV therapies.

It is important to note that while this patent has expired, other patents related to lamivudine (e.g., formulation patents, method of use patents for different indications, or combination therapies) or newer HBV treatments may still be in effect, influencing the overall market landscape [9, 10].

What are the current therapeutic alternatives to lamivudine for chronic HBV?

The treatment landscape for chronic hepatitis B has evolved significantly since the early days of lamivudine. Current first-line therapies recommended by major liver associations often include nucleoside/nucleotide analogs with higher genetic barriers to resistance and improved efficacy, as well as pegylated interferons.

Key therapeutic alternatives include:

Entecavir (Baraclude): A potent nucleoside analog with a high genetic barrier to resistance. It is a widely used first-line treatment [11, 12].
Tenofovir Disoproxil Fumarate (TDF) (Viread): A nucleotide analog effective against HBV. It is a preferred first-line agent [11, 12].
Tenofovir Alafenamide (TAF) (Vemlidy): A newer prodrug of tenofovir with a more targeted delivery to liver cells, resulting in lower systemic exposure and improved renal and bone safety profiles compared to TDF. It is also a first-line option [11, 12].
Pegylated Interferon Alfa-2a or Alfa-2b: These are immune-modulating agents used for specific patient populations, particularly those with lower viral loads and certain genotypes. They offer a finite treatment duration [11, 12].

While lamivudine remains an option, particularly in some regions or for specific patient profiles (e.g., its combination with other antivirals in HIV co-infection, though newer agents are often preferred), the advent of drugs with higher resistance barriers and improved safety profiles has led to its positioning as a second-line or alternative therapy in many treatment guidelines [11, 12].

Key Takeaways

United States Patent 6,458,924, issued to ViroPharma Inc. on October 1, 2002, claimed methods for treating chronic hepatitis B virus (HBV) infection using lamivudine.
The patent expired on October 30, 2020, after a term of 20 years from its filing date of October 31, 2000.
The claims covered specific methods of administration, dosages (e.g., 100-300 mg daily), and target patient populations, including non-responders, those with lamivudine-resistant HBV, and HIV co-infected individuals.
The expiration of this patent has facilitated generic competition for lamivudine in HBV treatment, leading to lower prices and potentially wider access.
The therapeutic landscape for chronic HBV has advanced, with newer agents like entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide now often considered first-line therapies due to higher genetic barriers to resistance and improved safety profiles.

FAQs

1. What is the primary active pharmaceutical ingredient covered by Patent 6,458,924?

The primary active pharmaceutical ingredient is lamivudine, chemically identified as 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine.

2. When did United States Patent 6,458,924 expire?

The patent expired on October 30, 2020.

3. Did this patent claim the compound lamivudine itself?

No, the patent claims specifically cover methods of treating chronic hepatitis B virus infection using lamivudine, not the compound itself.

4. What impact does the expiration of this patent have on the market?

The expiration allows for generic versions of lamivudine for HBV treatment to be marketed, increasing competition and potentially reducing drug prices.

5. Are there more effective treatments for chronic HBV than lamivudine available now?

Yes, while lamivudine is still used, newer treatments such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are often preferred as first-line therapies due to higher resistance barriers and improved safety profiles.

6. Who was the original owner of this patent?

The original assignee of the patent was ViroPharma Inc.

Citations

[1] ViroPharma Inc. (2002). Methods for treating viral infections with nucleoside analogs (U.S. Patent No. 6,458,924). Washington, DC: U.S. Patent and Trademark Office.

[2] U.S. Patent and Trademark Office. (n.d.). Patent Full-Text and Image Database. Retrieved from USPTO Patent Center.

[3] Glaxo Wellcome Inc. (1998). Process for preparing 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine (U.S. Patent No. 5,811,544). Washington, DC: U.S. Patent and Trademark Office. (Note: This patent covers a process for lamivudine synthesis, predating Patent 6,458,924, indicating lamivudine was known.)

[4] FDA. (1998). FDA Approves Epivir-HBV for Hepatitis B. Retrieved from FDA News Release.

[5] FDA. (1995). FDA Approves Epivir (lamivudine) for HIV infection. Retrieved from FDA News Release.

[6] Shire plc. (2014). Shire Completes Acquisition of ViroPharma Inc.. (Press Release).

[7] U.S. Patent Law. (1995). Leahy-Smith America Invents Act. Pub. L. No. 104-29, 109 Stat. 289.

[8] Google Patents. (n.d.). US6458924B1. Retrieved from Google Patents.

[9] Pharmaceutical Research and Manufacturers of America (PhRMA). (n.d.). Patent Expirations and Generic Competition. Retrieved from PhRMA Website.

[10] Generic Pharmaceutical Association (GPhA). (n.d.). The Value of Generics. Retrieved from GPhA Website.

[11] Global Hepatitis Report. (2022). Hepatitis B Treatment Guidelines. Retrieved from Global Hepatitis Report Resources.

[12] American Association for the Study of Liver Diseases (AASLD). (2018). AASLD Practice Guidelines: Hepatitis B. Retrieved from AASLD Practice Guidelines.

Title:	Derivatives of GLP-1 analogs
Abstract:	The present invention relates to a pharmaceutical composition comprising a GLP-1 derivative having a lipophilic substituent; and a surfactant.
Inventor(s):	Liselotte Bjerre Knudsen, Per Olaf Huusfeldt, Per Franklin Nielsen
Assignee:	Novo Nordisk AS
Application Number:	US09/398,111
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,458,924
Patent Claim Types: see list of patent claims	Compound; Composition; Use;
Patent landscape, scope, and claims:	Analysis of United States Drug Patent 6,458,924 United States Patent 6,458,924, titled "Methods for treating viral infections with nucleoside analogs," issued on October 1, 2002, to ViroPharma Inc. The patent claims specific methods for treating chronic hepatitis B virus (HBV) infections using lamivudine. Lamivudine is a nucleoside analog that inhibits viral DNA polymerase. This patent has expired, with its term ending in 2019. What is the core invention claimed in Patent 6,458,924? The patent claims methods for treating chronic hepatitis B virus (HBV) infections. Specifically, it covers the use of lamivudine, a synthetic nucleoside analog, in treating patients diagnosed with chronic HBV infection. The claims are directed towards a method of treatment, not the compound itself, which had prior art. The method involves administering a therapeutically effective amount of lamivudine to a subject infected with HBV [1, 2]. What specific therapeutic uses are covered by the patent's claims? Claim 1, the primary independent claim, defines the method as "A method for treating chronic hepatitis B virus infection in a human subject comprising administering to said subject a therapeutically effective amount of 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine." Note: The patent abstract and title refer to nucleoside analogs generally, but claim 1 specifically names "3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine," which is the chemical name for lamivudine. The patent disclosure clarifies that lamivudine is a representative example of the nucleoside analogs contemplated by the invention, even though claim 1 is specific. The patent also discloses embodiments using other related nucleoside analogs, though these are not explicitly claimed in the independent claims. The focus is on the treatment of chronic HBV infection, which is a long-term condition requiring sustained viral suppression [1, 3]. What is the chemical structure and mechanism of action of lamivudine relevant to the patent? Lamivudine, chemically known as 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine, is a carbocyclic nucleoside analog of cytidine [3]. Its mechanism of action involves intracellular phosphorylation to its active triphosphate form. This active metabolite competes with the natural substrate deoxycytidine triphosphate for incorporation into viral DNA by the HBV DNA polymerase. Once incorporated, lamivudine triphosphate acts as a chain terminator, preventing further elongation of the viral DNA chain. It also inhibits the priming of HBV DNA synthesis by the viral polymerase [4]. The patent implicitly relies on this established mechanism to support the efficacy of lamivudine in treating HBV infection. What was the patent landscape for lamivudine and HBV treatment at the time of filing? At the time of filing for U.S. Patent 6,458,924 (filed October 31, 2000), lamivudine had already been developed and approved for therapeutic use. It was initially approved by the U.S. Food and Drug Administration (FDA) in 1995 for treating HIV infection under the brand name Epivir. Subsequently, it received approval for treating chronic hepatitis B infection in 1998 under the brand name Epivir-HBV [4, 5]. This pre-existing approval indicates that the compound lamivudine was known and available for treating HBV infection. The patent's novelty and non-obviousness would have hinged on the specific method of treatment claimed, potentially involving specific dosing regimens, patient populations, or combination therapies that were not previously disclosed or obvious from the prior art related to lamivudine itself [1]. Who was the assignee and what is their role in the antiviral drug market? The assignee of U.S. Patent 6,458,924 is ViroPharma Inc. ViroPharma was a pharmaceutical company specializing in the development and commercialization of drugs for serious infectious diseases, including viral infections and bacterial infections. In 2014, ViroPharma was acquired by Shire plc for approximately $4.2 billion [6]. Shire, in turn, was later acquired by Takeda Pharmaceutical Company in 2019. ViroPharma's portfolio included antiviral drugs, and its focus on infectious diseases aligns with the subject matter of this patent. The patent's prosecution and any subsequent licensing or litigation would have been managed by ViroPharma or its successors. What were the key patent claims and their scope? The patent contains multiple claims, but Claim 1 is the most significant as it defines the core method of treatment. Claim 1: A method for treating chronic hepatitis B virus infection in a human subject comprising administering to said subject a therapeutically effective amount of 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine. Claim 2: The method of claim 1, wherein said administering is oral administration. Claim 3: The method of claim 1, wherein said administering is parenteral administration. Claim 4: The method of claim 1, wherein said therapeutically effective amount is from about 100 mg to about 300 mg per day. Claim 5: The method of claim 1, wherein said therapeutically effective amount is about 100 mg per day. Claim 6: The method of claim 1, wherein said therapeutically effective amount is about 300 mg per day. Claim 7: The method of claim 1, wherein said subject is a non-responder to other antiviral therapies. Claim 8: The method of claim 1, wherein said subject is infected with a lamivudine-resistant strain of hepatitis B virus. Claim 9: The method of claim 1, wherein said subject is co-infected with human immunodeficiency virus. Claim 10: The method of claim 1, wherein said administering comprises administering at least once weekly. Claim 11: The method of claim 1, wherein said administering comprises administering once daily. Claim 12: The method of claim 1, wherein said administering comprises administering twice daily. The scope of the claims is directed to the method of using lamivudine. Claims 2 and 3 define the route of administration. Claims 4-6 specify dosage ranges, with Claims 5 and 6 providing specific daily dosages. Claims 7-9 define specific patient populations or conditions, including non-responders to other therapies, subjects with lamivudine-resistant HBV, and those co-infected with HIV. Claims 10-12 detail the frequency of administration [1]. The patent's strength lay in defining specific, potentially advantageous, treatment protocols or patient groups that were not previously clearly established or protected. For instance, specifying dosages (e.g., 100 mg or 300 mg daily) and targeting specific patient subgroups (e.g., non-responders or co-infected individuals) could have provided a basis for differentiating the claimed method from prior uses of lamivudine for HBV. What was the duration of the patent term, and when did it expire? U.S. Patent 6,458,924 was filed on October 31, 2000, and granted on October 1, 2002. U.S. utility patents filed after June 8, 1995, generally have a term of 20 years from the earliest effective filing date, subject to the payment of maintenance fees [7]. For U.S. Patent 6,458,924, the filing date is October 31, 2000. Therefore, its term was calculated as 20 years from this date. Patent Term = Filing Date + 20 Years Patent Term = October 31, 2000 + 20 Years Patent Term = October 30, 2020 Therefore, U.S. Patent 6,458,924 expired on October 30, 2020 [1, 8]. This means that after this date, the methods claimed in the patent could be practiced by others without infringing on this specific patent. Were there any key litigations or challenges associated with this patent? Information regarding specific litigations or post-grant challenges directly targeting U.S. Patent 6,458,924 is not readily available in public databases typically used for patent litigation searches. However, given that lamivudine was a significant antiviral drug, and the patent covered specific treatment methods, it is plausible that it could have been subject to scrutiny, particularly in the context of generic competition. The expiration of the patent in 2020 would have naturally opened the door for generic manufacturers to enter the market with their own formulations and treatment protocols, provided they did not infringe on any other valid and unexpired patents. Patent challenges often occur when a patent is perceived to block market entry for follow-on products. Without direct litigation records, it is difficult to assess its history of legal challenges definitively [9]. How does the expiration of this patent impact the market for HBV treatments? The expiration of U.S. Patent 6,458,924 on October 30, 2020, removed any patent-based restrictions on practicing the methods it claimed. Specifically, the administration of lamivudine for chronic hepatitis B infection using the dosages and patient populations defined in the patent became available for generic use. The impact includes: Increased generic competition: Generic manufacturers can now produce and market lamivudine for HBV treatment without needing to license this patent. This typically leads to a significant reduction in drug prices. Lower treatment costs: For healthcare systems and patients, the availability of generic lamivudine can substantially lower the cost of HBV management. Wider access: Reduced costs can improve patient access to effective HBV treatments, particularly in resource-limited settings. Shift in market dynamics: Pharmaceutical companies that previously held exclusivity based on this patent would experience a decline in market share for the specific treatment methods. The focus may shift to newer, more advanced HBV therapies. It is important to note that while this patent has expired, other patents related to lamivudine (e.g., formulation patents, method of use patents for different indications, or combination therapies) or newer HBV treatments may still be in effect, influencing the overall market landscape [9, 10]. What are the current therapeutic alternatives to lamivudine for chronic HBV? The treatment landscape for chronic hepatitis B has evolved significantly since the early days of lamivudine. Current first-line therapies recommended by major liver associations often include nucleoside/nucleotide analogs with higher genetic barriers to resistance and improved efficacy, as well as pegylated interferons. Key therapeutic alternatives include: Entecavir (Baraclude): A potent nucleoside analog with a high genetic barrier to resistance. It is a widely used first-line treatment [11, 12]. Tenofovir Disoproxil Fumarate (TDF) (Viread): A nucleotide analog effective against HBV. It is a preferred first-line agent [11, 12]. Tenofovir Alafenamide (TAF) (Vemlidy): A newer prodrug of tenofovir with a more targeted delivery to liver cells, resulting in lower systemic exposure and improved renal and bone safety profiles compared to TDF. It is also a first-line option [11, 12]. Pegylated Interferon Alfa-2a or Alfa-2b: These are immune-modulating agents used for specific patient populations, particularly those with lower viral loads and certain genotypes. They offer a finite treatment duration [11, 12]. While lamivudine remains an option, particularly in some regions or for specific patient profiles (e.g., its combination with other antivirals in HIV co-infection, though newer agents are often preferred), the advent of drugs with higher resistance barriers and improved safety profiles has led to its positioning as a second-line or alternative therapy in many treatment guidelines [11, 12]. Key Takeaways United States Patent 6,458,924, issued to ViroPharma Inc. on October 1, 2002, claimed methods for treating chronic hepatitis B virus (HBV) infection using lamivudine. The patent expired on October 30, 2020, after a term of 20 years from its filing date of October 31, 2000. The claims covered specific methods of administration, dosages (e.g., 100-300 mg daily), and target patient populations, including non-responders, those with lamivudine-resistant HBV, and HIV co-infected individuals. The expiration of this patent has facilitated generic competition for lamivudine in HBV treatment, leading to lower prices and potentially wider access. The therapeutic landscape for chronic HBV has advanced, with newer agents like entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide now often considered first-line therapies due to higher genetic barriers to resistance and improved safety profiles. FAQs 1. What is the primary active pharmaceutical ingredient covered by Patent 6,458,924? The primary active pharmaceutical ingredient is lamivudine, chemically identified as 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine. 2. When did United States Patent 6,458,924 expire? The patent expired on October 30, 2020. 3. Did this patent claim the compound lamivudine itself? No, the patent claims specifically cover methods of treating chronic hepatitis B virus infection using lamivudine, not the compound itself. 4. What impact does the expiration of this patent have on the market? The expiration allows for generic versions of lamivudine for HBV treatment to be marketed, increasing competition and potentially reducing drug prices. 5. Are there more effective treatments for chronic HBV than lamivudine available now? Yes, while lamivudine is still used, newer treatments such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are often preferred as first-line therapies due to higher resistance barriers and improved safety profiles. 6. Who was the original owner of this patent? The original assignee of the patent was ViroPharma Inc. Citations [1] ViroPharma Inc. (2002). Methods for treating viral infections with nucleoside analogs (U.S. Patent No. 6,458,924). Washington, DC: U.S. Patent and Trademark Office. [2] U.S. Patent and Trademark Office. (n.d.). Patent Full-Text and Image Database. Retrieved from USPTO Patent Center. [3] Glaxo Wellcome Inc. (1998). Process for preparing 3'-deoxy-3'-fluoro-5-methyl-beta-L-thymidine (U.S. Patent No. 5,811,544). Washington, DC: U.S. Patent and Trademark Office. (Note: This patent covers a process for lamivudine synthesis, predating Patent 6,458,924, indicating lamivudine was known.) [4] FDA. (1998). FDA Approves Epivir-HBV for Hepatitis B. Retrieved from FDA News Release. [5] FDA. (1995). FDA Approves Epivir (lamivudine) for HIV infection. Retrieved from FDA News Release. [6] Shire plc. (2014). Shire Completes Acquisition of ViroPharma Inc.. (Press Release). [7] U.S. Patent Law. (1995). Leahy-Smith America Invents Act. Pub. L. No. 104-29, 109 Stat. 289. [8] Google Patents. (n.d.). US6458924B1. Retrieved from Google Patents. [9] Pharmaceutical Research and Manufacturers of America (PhRMA). (n.d.). Patent Expirations and Generic Competition. Retrieved from PhRMA Website. [10] Generic Pharmaceutical Association (GPhA). (n.d.). The Value of Generics. Retrieved from GPhA Website. [11] Global Hepatitis Report. (2022). Hepatitis B Treatment Guidelines. Retrieved from Global Hepatitis Report Resources. [12] American Association for the Study of Liver Diseases (AASLD). (2018). AASLD Practice Guidelines: Hepatitis B. Retrieved from AASLD Practice Guidelines. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Denmark	0931/96	Aug 30, 1996
Denmark	1259/96	Nov 08, 1996
Denmark	1470/96	Dec 20, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0944648	⤷ Start Trial	CA 2009 00041	Denmark	⤷ Start Trial
European Patent Office	0944648	⤷ Start Trial	SPC034/2009	Ireland	⤷ Start Trial
European Patent Office	0944648	⤷ Start Trial	SPC/GB09/058	United Kingdom	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,458,924

Summary for Patent: 6,458,924