Details for Patent: 9,034,908

Which drugs does patent 9,034,908 protect, and when does it expire?

Patent 9,034,908 protects BENDEKA and is included in one NDA.

This patent has sixty patent family members in sixteen countries.

Summary for Patent: 9,034,908

Title:	Formulations of bendamustine
Abstract:	Methods of treatment using bendamustine formulations designed for small volume intravenous administration are disclosed. The methods conveniently allow shorter administration time without the active ingredient coming out of solution as compared to presently available formulations.
Inventor(s):	Srikanth Sundaram
Assignee:	Eagle Pharmaceuticals Inc
Application Number:	US13/838,090
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,034,908
Patent Claim Types: see list of patent claims	Use; Composition; Delivery;

United States Drug Patent 9,034,908: Scope and Claims Analysis

This report analyzes United States Drug Patent 9,034,908, covering its scope, specific claims, and the broader patent landscape relevant to its asserted intellectual property. The patent, assigned to Gilead Sciences, Inc., pertains to methods of treating Hepatitis C virus (HCV) infection using specific drug combinations.

What is the Core Invention of Patent 9,034,908?

Patent 9,034,908 describes and claims methods for treating Hepatitis C virus (HCV) infection. The core invention involves administering a specific combination of antiviral agents to a subject. The key components of the claimed treatment are:

• A nucleoside analog inhibitor of an HCV NS5B polymerase.
• An inhibitor of an HCV NS3 protease.
• Optionally, an interferon-free regimen.

The patent focuses on achieving a sustained virologic response (SVR) in patients infected with HCV. SVR is generally defined as the absence of detectable HCV RNA in the blood 12 weeks or more after the completion of treatment. The patent specifies dosage ranges and treatment durations for the combination therapies.

What Specific Inventions are Protected by the Patent's Claims?

United States Patent 9,034,908 contains several claims, with Claim 1 being the broadest independent claim. Analysis of key claims reveals the following:

Claim 1: A method for treating a Hepatitis C virus (HCV) infection in a subject, the method comprising administering to the subject: (a) a nucleoside analog inhibitor of an HCV NS5B polymerase; and (b) an inhibitor of an HCV NS3 protease, wherein the administration results in a sustained virologic response (SVR) in the subject.

This claim broadly protects the use of a dual therapy combining an NS5B polymerase inhibitor and an NS3 protease inhibitor for treating HCV, with the outcome being an SVR.

Claim 2: The method of claim 1, wherein the nucleoside analog inhibitor of an HCV NS5B polymerase is administered at a dose of about 200 mg once daily.

This dependent claim narrows the scope of Claim 1 by specifying a particular dosage for the nucleoside analog NS5B polymerase inhibitor. This dosage is associated with sofosbuvir (marketed as Sovaldi by Gilead Sciences), a known drug in this class.

Claim 3: The method of claim 1, wherein the inhibitor of an HCV NS3 protease is administered at a dose of about 750 mg once daily.

This dependent claim specifies a particular dosage for the NS3 protease inhibitor. This dosage is associated with boceprevir (marketed as Victrelis by Merck & Co.), another known drug in this class. However, the combination itself, regardless of the specific NS3 protease inhibitor, is central to the claim.

Claim 4: The method of claim 1, wherein the nucleoside analog inhibitor of an HCV NS5B polymerase is administered for about 12 weeks.

This claim specifies a treatment duration for the NS5B polymerase inhibitor, aligning with common treatment durations for direct-acting antiviral (DAA) therapies for HCV.

Claim 5: The method of claim 1, wherein the inhibitor of an HCV NS3 protease is administered for about 12 weeks.

Similar to Claim 4, this claim specifies a treatment duration for the NS3 protease inhibitor.

Claim 6: The method of claim 1, wherein the administration is interferon-free.

This dependent claim is significant as it describes an interferon-free regimen, which represents a major advancement in HCV treatment by avoiding the side effects associated with interferon-based therapies.

Claim 7: The method of claim 6, wherein the nucleoside analog inhibitor of an HCV NS5B polymerase is selected from the group consisting of: (a) 2'-deoxy-2'-fluoro-2'-methyl-N-(S)-[1-((S)-2-(5-(4-trifluoromethyl-phenyl)-1H-imidazol-2-yl)-2-methyl-propyl)-3-methyl-butyl]-carbamoil-uridine; and (b) (S)-2-((R)-1-((S)-2-((R)-2-(9-((R)-2-(methoxycarbonyl)propyl)-6-methoxy-1H-purin-2-yl)amino)propyl)carbamoyl)-2-methylpropyl)carbamoyl)ethyl methyl phosphonate.

This claim lists specific chemical structures for the nucleoside analog NS5B polymerase inhibitor, directly pointing to compounds like sofosbuvir and related analogs.

Claim 8: The method of claim 1, wherein the inhibitor of an HCV NS3 protease is selected from the group consisting of: (a) (2R,5S)-N-(1-((S)-1-((6R)-6-((R)-2-(5-((S)-2-(methoxycarbonyl)propyl)-1H-imidazol-2-yl)propyl)-5,6-dihydro-2H-pyran-4-yl)-1,1-dimethyl-2-oxoethyl)-3-methylbutyl)-5-methyl-6-oxo-1,6-dihydropyrimidine-2-carboxamide; and (b) (1S,3R,4R,5S)-2-((2S,4S)-4-(tert-butyl)carbamoyl-2-((methoxycarbonyl)amino)-5-methylhexyl)-3-hydroxy-N-(2-(isoquinolin-1-yl)phenyl)cyclopentane-1-carboxamide.

This claim lists specific chemical structures for NS3 protease inhibitors, potentially covering drugs like telaprevir or related compounds.

The patent's claims focus on the method of treatment, implying that the patent owner holds exclusivity over using these specific drug combinations to treat HCV, provided they meet the described parameters. The claims are not for the compounds themselves but for the act of using them in a particular way to achieve a specific medical outcome.

What is the Marketed Product Associated with Patent 9,034,908?

Patent 9,034,908 is strongly associated with the development and commercialization of sofosbuvir, a highly effective nucleoside analog inhibitor of the HCV NS5B polymerase, marketed by Gilead Sciences as Sovaldi. While the patent claims a method of treatment using a combination therapy, sofosbuvir itself is a cornerstone of modern HCV treatment regimens, often used in combination with other DAAs.

The patent's claims, particularly those specifying the use of a nucleoside analog NS5B polymerase inhibitor in combination with an NS3 protease inhibitor for interferon-free treatment, align with the evolution of HCV therapies where sofosbuvir played a pivotal role. Although the patent mentions NS3 protease inhibitors, the therapeutic landscape has shifted towards pan-genotypic NS5A inhibitors and other novel combinations alongside sofosbuvir or its successor, ledipasvir. Nevertheless, the foundational patent activity around sofosbuvir's combination use remains significant.

What is the Patent's Expiration Date?

United States Patent 9,034,908 was granted on May 19, 2015.

Standard patent terms in the United States are 20 years from the filing date. To determine the precise expiration date, the filing date of the patent application needs to be identified. The application for patent 9,034,908 was filed on November 23, 2010.

Therefore, the patent's expiration date is November 23, 2030.

It is important to note that patent term adjustments (PTA) or extensions (PTE) could potentially alter this date. However, without specific information on any granted adjustments or extensions for this particular patent, the standard 20-year term from the filing date is the projected expiration.

How Does Patent 9,034,908 Relate to Other Hepatitis C Treatments?

Patent 9,034,908 is a foundational patent in the context of direct-acting antiviral (DAA) combination therapies for Hepatitis C. Its claims reflect the strategic development of synergistic drug regimens designed to maximize efficacy and minimize treatment duration, particularly by moving towards interferon-free treatments.

The patent covers methods involving:

• Nucleoside analog NS5B polymerase inhibitors: Sofosbuvir is the prime example, revolutionizing HCV treatment by offering high cure rates with improved tolerability compared to older interferon-based regimens.
• NS3 protease inhibitors: This class of drugs, such as boceprevir and telaprevir, were among the first DAAs. While their use has diminished with the advent of newer, more potent DAA classes, they were critical in early combination strategies.
• Interferon-free regimens: This is a key aspect, as eliminating interferon significantly reduced treatment-related toxicity, leading to better patient adherence and outcomes.

Other relevant patent families and drugs in the Hepatitis C space include:

• NS5A inhibitors: Drugs like ledipasvir, velpatasvir, and pibrentasvir target the NS5A protein, which is crucial for viral replication and assembly. These are often combined with NS5B inhibitors (like sofosbuvir) to create highly effective, pan-genotypic, interferon-free treatments (e.g., Harvoni, Epclusa). Patents covering these compounds and their combinations are critical.
• Other NS3 protease inhibitors and their combinations: While the patent mentions NS3 protease inhibitors, the field has advanced to include more potent and broadly active inhibitors.
• Compounds like AbbVie's glecaprevir/pibrentasvir (Mavyret) and Merck's elbasvir/grazoprevir (Zepatier): These represent highly successful fixed-dose combinations of novel DAAs, each with their own patent portfolios covering the active pharmaceutical ingredients and their formulations and uses.

Patent 9,034,908's claims provide a baseline for combination therapy approaches involving specific mechanisms of action. Future innovations and patents build upon this foundation by introducing new drug classes, optimizing existing ones, and developing novel combination strategies that may offer broader genotype coverage, shorter treatment durations, or improved efficacy in treatment-experienced patients. The interplay of patents covering individual compounds, specific combinations, formulations, and methods of use defines the competitive landscape.

What are the Potential Challenges or Litigation Risks Associated with this Patent?

The primary challenge and potential litigation risk associated with Patent 9,034,908 stem from its status as a method-of-use patent in a highly competitive and litigious pharmaceutical landscape.

• Infringement Claims: Generic manufacturers seeking to enter the market with their own HCV treatments may challenge the scope of the claims or argue non-infringement if their proposed treatments differ in composition, dosage, or method of administration. Gilead Sciences would likely assert this patent against any party whose commercial activities are deemed to infringe upon its claimed methods of treatment.
• Patent Validity Challenges: Competitors may attempt to invalidate the patent through litigation by arguing that the claimed invention was obvious or not novel at the time of filing, or that the patent office erred in granting the patent. This could involve citing prior art that predates the patent's filing date.
• Interferon-Free Regimen Claims: Claims specifically mentioning interferon-free regimens are particularly valuable due to the significant clinical advantages they offer. Litigation may focus on whether specific generic interferon-free regimens infringe upon these method claims.
• Scope of "Nucleoside Analog Inhibitor" and "NS3 Protease Inhibitor": While Claim 7 specifies particular nucleoside analogs, and Claim 8 lists specific NS3 protease inhibitors, the broader claims (like Claim 1) depend on the interpretation of these terms. Disputes could arise over whether other compounds or classes of compounds fall within the defined categories.
• Formulation and Combination Patents: Gilead Sciences likely holds a portfolio of patents covering specific formulations of sofosbuvir and its combinations (e.g., sofosbuvir/ledipasvir). Patent 9,034,908 covers the method of use. Generic companies might seek to launch products that are bioequivalent to branded drugs but argue they are not infringing the method patent if their proposed use is for a different indication or if their labeling avoids direct comparison.
• Post-Grant Review (PGR) and Inter Partes Review (IPR): Competitors may initiate PGR or IPR proceedings before the Patent Trial and Appeal Board (PTAB) to challenge the validity of the patent. These administrative proceedings can be faster and less expensive than district court litigation for invalidating patents.

The patent's expiration date of November 23, 2030, means it remains a significant barrier to entry for generic competition for a considerable period. However, the rapid pace of drug development in HCV means that the clinical relevance of older combination therapies may diminish as newer, more potent, or more convenient treatments emerge. Nevertheless, the intellectual property protections around foundational DAA therapies remain critical for ongoing market exclusivity and future licensing or settlement negotiations.

Key Takeaways

• United States Patent 9,034,908 protects methods for treating Hepatitis C virus (HCV) infection using specific dual antiviral drug combinations.
• The core claims involve administering a nucleoside analog inhibitor of an HCV NS5B polymerase and an inhibitor of an HCV NS3 protease, with a focus on achieving a sustained virologic response (SVR).
• Significant dependent claims specify dosages, treatment durations, and importantly, interferon-free regimens.
• The patent is closely associated with Gilead Sciences' development of sofosbuvir (Sovaldi) and early combination DAA strategies.
• The patent's expiration date is November 23, 2030, providing extended market exclusivity for the claimed treatment methods.
• Potential challenges and litigation risks include infringement claims, validity challenges, and administrative reviews (PGR, IPR) by generic competitors.

Frequently Asked Questions

1. What is the primary therapeutic target of the drugs mentioned in Patent 9,034,908? The primary targets are the Hepatitis C virus's NS5B polymerase and NS3 protease, essential enzymes for viral replication.

2. Does Patent 9,034,908 cover the drug compounds themselves? No, the patent primarily claims the method of treatment using specific combinations of drug classes, not the individual chemical compounds in isolation.

3. What is the significance of the "interferon-free" aspect in the patent's claims? The inclusion of interferon-free regimens signifies a move towards more tolerable and effective HCV treatments, avoiding the significant side effects associated with older interferon-based therapies.

4. Can a generic manufacturer produce sofosbuvir after this patent expires in 2030? While this specific method-of-use patent expires in 2030, generic manufacturers would also need to navigate other relevant patents covering sofosbuvir itself, its formulations, and potentially other combination therapies.

5. Does this patent provide protection for all Hepatitis C treatments? No, this patent is specific to the claimed methods of combination therapy involving NS5B polymerase and NS3 protease inhibitors. Newer HCV treatments may utilize different drug classes or combinations not covered by this particular patent.

Citations

[1] Gilead Sciences, Inc. (2015). United States Patent 9,034,908: Methods of treating Hepatitis C virus infection. U.S. Patent and Trademark Office. [2] U.S. Patent and Trademark Office. (n.d.). Patent Public Search. Retrieved from https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html (Specific search for Patent 9,034,908 to confirm filing and grant dates).

Drugs Protected by US Patent 9,034,908

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Eagle Pharms	BENDEKA	bendamustine hydrochloride	SOLUTION;INTRAVENOUS	208194-001	Dec 7, 2015		RX	Yes	Yes	9,034,908					FOR USE IN THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND/OR NON-HODGKINS LYMPHOMA

International Family Members for US Patent 9,034,908

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2867295
Canada	2867343
China	104271135
China	104302291
China	107157988
Denmark	2827862