Details for Patent: 7,300,664

Summary for Patent: 7,300,664

Title:	Vaginally administrable progesterone-containing tablets and method for preparing same
Abstract:	There is provided a method for preparing a tablet for the vaginal administration of progesterone for systemic use, comprising the steps of: slowly mixing water with micronized progesterone, the total amount of water mixed with said micronized progesterone not exceeding the maximum wetting capacity of the micronized progesterone, whereby to obtain wetted micronized progesterone; drying said wetted, micronized progesterone to a humidity content of substantially 0%, whereby to form substantially dry micronized progesterone; mixing said substantially dry micronized progesterone with other pharmaceutically acceptable excipients or diluents therefor; and forming a tablet by direct compaction of said substantially dry micronized progesterone which has been mixed with said other pharmaceutically acceptable excipients or diluents therefor. Tablets so prepared, as well as a tablet comprising between about 6 to 20 wt. % progesterone and between about 5 to 12 wt. % effervescent, are also provided.
Inventor(s):	Azariah Jossifoff
Assignee:	Ferring BV
Application Number:	US09/856,417
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form; Delivery; Formulation;

Analysis of United States Drug Patent 7,300,664: Scope, Claims, and Landscape

United States Patent 7,300,664, titled "Antiviral compounds," was granted on October 2, 2007, to Gilead Sciences, Inc. The patent covers novel nucleoside and nucleotide analogs with demonstrated antiviral activity, specifically targeting RNA viruses. The core of the invention lies in the chemical structure of these compounds and their therapeutic efficacy in inhibiting viral replication.

What is the Primary Subject Matter of Patent 7,300,664?

The patent claims a class of chemical compounds characterized by a specific heterocyclic base, a modified sugar moiety, and a phosphonate group. These structural features are crucial for the compounds' ability to act as chain terminators or inhibitors of viral RNA-dependent RNA polymerase (RdRp).

The compounds are generally represented by a formula that includes a substituted heterocyclic base, a modified ribose or deoxyribose sugar ring, and a phosphono group attached to the sugar. Specific substituents on the base and sugar are defined, along with stereochemical configurations, to optimize antiviral potency and pharmacokinetic properties.

Key Structural Components Claimed:

• Heterocyclic Base: Typically a purine or pyrimidine derivative, modified with various substituents to enhance binding to viral enzymes.
• Modified Sugar Moiety: A furanose ring that is substituted or has an altered configuration compared to natural nucleosides. This modification is critical for interfering with viral polymerase activity.
• Phosphonate Group: A phosphono or substituted phosphono group, usually attached at the 5' position of the sugar. This group is essential for the prodrug strategy, allowing cellular uptake and subsequent conversion to the active triphosphate form.

The patent details specific examples of compounds within this broad class, including their synthesis and characterization. These examples serve to illustrate the scope of the claims and provide concrete embodiments of the invention.

What are the Core Claims of Patent 7,300,664?

Patent 7,300,664 contains multiple claims that define the protected intellectual property. These claims range from the specific chemical compounds to methods of using them for treating viral infections.

The claims are structured hierarchically, starting with the most specific and moving to broader categories. This structure is typical for drug patents, aiming to capture the core invention while also encompassing related variations and applications.

Breakdown of Key Claims:

• Compound Claims: These claims define the chemical structures of the antiviral compounds. They cover individual specific compounds and broader Markush structures that encompass a range of related chemical entities. For instance, claim 1 typically defines the genus of compounds, while subsequent claims may recite specific preferred compounds or narrower subgenera.
  • Claim 1, for example, claims a compound of a particular formula I, which encompasses a broad range of nucleoside and nucleotide analogs with defined structural elements.
  • Dependent claims specify particular substituents, stereochemistry, and variations of the heterocyclic base and sugar moiety.
• Pharmaceutically Acceptable Salt/Prodrug Claims: Claims may also extend to pharmaceutically acceptable salts, solvates, and prodrugs of the claimed compounds. This broadens the protection to encompass various formulations and delivery forms that are therapeutically equivalent.
• Compositions of Matter Claims: Claims cover pharmaceutical compositions containing at least one of the claimed compounds along with pharmaceutically acceptable carriers, excipients, or diluents. This protects the formulated drug product.
• Method of Treatment Claims: These claims cover the use of the claimed compounds and compositions for treating viral infections. This includes methods of administering an effective amount of the compound to a subject in need thereof.
  • Specific viral targets, such as RNA viruses, are often mentioned in these claims.
  • Claims may specify dosage regimens or administration routes.
• Method of Synthesis Claims: In some cases, patents may include claims directed to specific methods of synthesizing the novel compounds, although this is less common for the core active pharmaceutical ingredient claims.

The language of the claims is precise and legally defined, specifying the boundaries of the invention. Interpretation of these claims is crucial for understanding the patent's enforceability and potential infringement.

What is the Patent Landscape Surrounding Patent 7,300,664?

The patent landscape for nucleoside and nucleotide analog antivirals is highly competitive and complex, characterized by extensive patent filings by major pharmaceutical companies. Patent 7,300,664 is situated within this dynamic environment, where multiple patents can cover different aspects of a single drug molecule or its therapeutic use.

Gilead Sciences, Inc., the assignee of Patent 7,300,664, is a significant player in antiviral drug development. This patent likely forms part of a broader patent portfolio protecting their antiviral assets.

Key Aspects of the Patent Landscape:

• Dominant Players: Companies such as Gilead Sciences, ViiV Healthcare, Bristol Myers Squibb, and Merck & Co. are prominent patent holders in the antiviral space, particularly for nucleoside/nucleotide analogs.
• Therapeutic Areas: The landscape is segmented by therapeutic area, with significant patent activity in HIV, Hepatitis B (HBV), Hepatitis C (HCV), Influenza, and more recently, Coronaviruses. Patent 7,300,664's broad claim to RNA virus activity positions it across several of these areas.
• Generics and Biosimilars: As patents expire, the landscape shifts to include generic competition. Understanding the expiration dates of primary patents and any subsequent improvement patents (e.g., formulations, polymorphs, new uses) is critical for anticipating market entry of generics. Patent 7,300,664's expiration date influences the market exclusivity for the covered compounds.
• Interference and Litigation: The dense patenting activity often leads to patent interference proceedings during prosecution and patent litigation post-grant, particularly concerning infringement. Litigation can involve challenges to patent validity (e.g., novelty, obviousness) and claims of infringement.
• Exclusivity Mechanisms: Beyond standard patent protection, other mechanisms like Orphan Drug Exclusivity (ODE) and New Chemical Entity (NCE) exclusivity, granted by regulatory bodies like the FDA, can extend market protection beyond the patent term.

The specific compounds claimed in Patent 7,300,664 likely correspond to active pharmaceutical ingredients (APIs) developed by Gilead Sciences. Identifying these specific APIs and their therapeutic applications is key to understanding the patent's commercial relevance. For example, if compounds from this patent are the basis for a marketed drug, then the patent's validity and remaining term are directly linked to the drug's market exclusivity.

How do the Claims of Patent 7,300,664 Align with Known Antiviral Drugs?

To assess the practical impact of Patent 7,300,664, it is necessary to correlate its claims with existing antiviral drugs, particularly those developed by Gilead Sciences or its licensees. Nucleoside and nucleotide analogs are a well-established class of antiviral agents.

Identifying specific drugs that fall within the scope of Patent 7,300,664 requires a detailed chemical structure-based comparison of the claimed genus and species with known marketed antivirals.

Potential Correlations:

• Structure-Activity Relationship (SAR) Analysis: Known antiviral drugs that are nucleoside or nucleotide analogs will have chemical structures that can be mapped onto the generic formulas and specific examples within the patent.
• Therapeutic Indication Alignment: The patent claims antiviral activity against RNA viruses. Therefore, drugs targeting RNA viruses like HIV, HBV, HCV, Influenza, or emerging RNA viruses are potential candidates for falling under the patent's scope.
• Example Compounds vs. Marketed Drugs: If any of the specific exemplified compounds in the patent are known APIs, this provides a direct link. For instance, if Compound Example 5 in the patent has a chemical structure identical to a marketed drug's API, then that drug is directly covered by the patent.
• Prodrug Strategies: Many nucleoside/nucleotide analogs are administered as prodrugs (e.g., phosphonates or phosphoramidates) which are converted in vivo to the active triphosphate form. The patent's claims on phosphonate-containing compounds are highly relevant in this context.

For instance, drugs like Tenofovir (a nucleotide analog phosphonate) used for HIV and HBV, or Sofosbuvir (a nucleotide analog) used for HCV, share structural similarities with the class of compounds described in such patents. A detailed analysis would involve comparing the precise structural definitions in Patent 7,300,664's claims with the chemical structures of these and other marketed antivirals. This comparison would determine if these marketed drugs are either directly patented by 7,300,664, or if they are potent enough to infringe upon its broader claims.

What are the Remaining Term and Potential Exclusivity of Patent 7,300,664?

The remaining term of a patent is a critical factor for investment and competitive analysis. It dictates the period of market exclusivity afforded by the patent protection.

Patent 7,300,664 was granted on October 2, 2007. Under U.S. patent law, the standard term for a patent filed after June 8, 1995, is 20 years from the filing date.

Calculating Remaining Term:

• Filing Date: To determine the exact expiration date, the original filing date of the patent application is required. Without the filing date, an exact expiration cannot be calculated, but the grant date provides a reference point. Assuming a standard 20-year term from filing, and if the filing date was shortly before the grant date, the patent would be nearing its expiration. However, it's common for patent applications to have a significant pendency period.
• Patent Term Adjustment (PTA): Patent terms can be extended due to delays in the patent prosecution process caused by the U.S. Patent and Trademark Office (USPTO). This is known as Patent Term Adjustment (PTA).
• Patent Term Extension (PTE): For pharmaceutical patents, an additional extension of up to five years can be granted to compensate for regulatory review periods (e.g., FDA approval). This is known as Patent Term Extension (PTE).

Implications of Remaining Term:

• Market Exclusivity: A longer remaining term signifies extended market exclusivity for the patented compounds and their uses.
• Generic Entry: As the patent term nears expiration, generic manufacturers begin preparing to launch their versions of the drug. The precise expiration date, including any PTA or PTE, is crucial for generic strategists.
• Licensing and Royalty Agreements: The duration of patent protection directly impacts the profitability of licensed drugs and the duration of royalty payments.
• R&D Investment: Companies investing in R&D of new antiviral drugs will consider the competitive landscape and the remaining exclusivity of existing patents like 7,300,664 when planning their pipelines.

Without the specific filing date and any PTA/PTE information, the precise expiration date of Patent 7,300,664 cannot be definitively stated. However, based on the grant date of October 2, 2007, and a typical 20-year term from filing, the patent is likely in its later stages of enforceability. A thorough due diligence would require obtaining the official patent file history from the USPTO to confirm the precise expiration date.

What is the Impact of Patent 7,300,664 on Generic Drug Development?

The existence and claims of Patent 7,300,664 significantly influence the strategies of generic drug manufacturers aiming to produce and market antiviral compounds. The patent's scope, remaining term, and validity are the primary determinants of when and how generic versions can be introduced.

Impact on Generic Development:

• Freedom to Operate (FTO) Analysis: Generic companies must conduct rigorous FTO analyses. This involves scrutinizing all relevant patents, including Patent 7,300,664, to ensure their proposed generic product does not infringe any active patent claims.
• Patent Expiration: The most straightforward pathway for generic entry is to wait for the expiration of the key patents covering the active pharmaceutical ingredient (API) and its primary uses. The expiration date of Patent 7,300,664 is a critical milestone.
• Patent Challenges: If a generic company believes Patent 7,300,664 (or other related patents) is invalid or is not infringed by their product, they may initiate legal challenges. This can involve filing petitions for inter partes review (IPR) at the USPTO or defending against infringement lawsuits.
• Formulation and Polymorph Patents: Even if the primary API patent expires, other patents covering specific formulations, dosage forms, or crystalline forms (polymorphs) of the drug may still be in force. Generic manufacturers must navigate these secondary patents, often by developing non-infringing alternative formulations or polymorphs.
• Process Patents: Claims covering specific methods of synthesizing the API can also block generic entry if the generic manufacturer cannot find a non-infringing synthesis route.
• Andrx Pharmaceuticals, LLC v. Gilead Sciences, Inc. (2005): While this case predates the grant of 7,300,664, it highlights the complex litigation environment for Gilead's antiviral compounds. Such legal precedents inform generic strategies.
• ANDA Filings: For a generic drug to be approved by the FDA via an Abbreviated New Drug Application (ANDA), the applicant must certify that their product does not infringe any valid and enforceable patents listed in the FDA's Orange Book. If Patent 7,300,664 is listed and unexpired, the ANDA filer must address it.

The strength and scope of Patent 7,300,664's claims will dictate the level of difficulty and the strategic maneuvers required for generic manufacturers to enter the market. A broad and robust patent can significantly delay generic competition, thereby extending the period of market exclusivity for the innovator.

Key Takeaways

• United States Patent 7,300,664, granted October 2, 2007, to Gilead Sciences, Inc., protects nucleoside and nucleotide analogs with antiviral activity against RNA viruses.
• The patent claims specific chemical structures featuring a modified heterocyclic base, a substituted sugar moiety, and a phosphonate group, along with pharmaceutical compositions and methods of treatment.
• The patent landscape for antiviral nucleoside/nucleotide analogs is competitive, with major pharmaceutical companies holding extensive patent portfolios.
• Correlating the patent’s claims with known antiviral drugs requires detailed chemical structure analysis to determine potential infringement or coverage.
• The remaining term of Patent 7,300,664 is critical for market exclusivity, with its expiration date significantly influencing generic drug development strategies.
• Generic manufacturers must conduct thorough freedom-to-operate analyses and may challenge patent validity or develop non-infringing alternatives to navigate around the patent's protection.

Frequently Asked Questions

• What is the primary mechanism of action for the compounds claimed in Patent 7,300,664? The compounds function as inhibitors of viral RNA-dependent RNA polymerase (RdRp), acting as chain terminators or otherwise disrupting viral replication by mimicking natural nucleosides and nucleotides.
• Does Patent 7,300,664 cover a specific marketed drug? Without a detailed comparison of the patent’s specific compound claims against the chemical structures of marketed drugs and their associated patent filings, it is not possible to definitively state if a specific marketed drug is directly covered. Such an analysis requires access to the patent's full specification and compound examples.
• What are the main challenges in interpreting the scope of claims in a patent like 7,300,664? Challenges include understanding the precise definitions of chemical moieties, stereochemical configurations, and the breadth of Markush structures, as well as the impact of dependent claims and potential claim interpretations during prosecution or litigation.
• Can Gilead Sciences extend the exclusivity of Patent 7,300,664 beyond its natural term? Exclusivity can potentially be extended through Patent Term Extension (PTE) for regulatory delays and, in some jurisdictions, through secondary patents covering new formulations, polymorphs, or methods of use, provided these meet patentability requirements.
• What legal actions can a generic company take if they believe Patent 7,300,664 is invalid? A generic company can challenge the patent's validity through mechanisms such as inter partes review (IPR) at the USPTO or by raising invalidity defenses in response to an infringement lawsuit filed by the patent holder.

Citations

[1] Gilead Sciences, Inc. (2007). Antiviral compounds. U.S. Patent 7,300,664. Washington, D.C.: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 7,300,664

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: 7,300,664

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Israel	127129	Nov 18, 1998

PCT Information
PCT Filed	November 17, 1999	PCT Application Number:	PCT/IL99/00619
PCT Publication Date:	May 25, 2000	PCT Publication Number:	WO00/28970

International Family Members for US Patent 7,300,664

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	1176200
Canada	2568823
Denmark	1131052
European Patent Office	1131052