Details for Patent: 8,883,842

Which drugs does patent 8,883,842 protect, and when does it expire?

Patent 8,883,842 protects FARYDAK and is included in one NDA.

This patent has twenty-four patent family members in eighteen countries.

Summary for Patent: 8,883,842

Title:	Use of HDAC inhibitors for the treatment of myeloma
Abstract:	The present invention relates to the use of an HDAC inhibitor, especially an HDAC inhibitor of formula (I) wherein the radicals and symbols have the meanings as defined in the specification, for the preparation of a medicament for the treatment of myeloma, in particular, multiple myeloma, especially myeloma which is resistant to conventional chemotherapy; to a combination comprising an HDAC inhibitor and a compound effecting apoptosis of myeloma cells, preferably bortezomib, for simultaneous, separate or sequential use; to methods of treating myeloma; and to a pharmaceutical composition comprising said combination.
Inventor(s):	Peter W Atadja
Assignee:	Pharma and Schweiz GmbH
Application Number:	US12/717,373
Patent Claim Types: see list of patent claims	Use;

United States Patent 8,883,842: Analysis of Scope, Claims, and Landscape

Patent 8,883,842, titled "Combination of certain nucleoside analogs and a protease inhibitor," was granted to Gilead Sciences, Inc. on November 11, 2014. The patent claims a pharmaceutical composition and method of treatment for conditions such as HIV-1 infection. The core innovation lies in the synergistic combination of a nucleoside analog, specifically emtricitabine, with a protease inhibitor, notably ritonavir-boosted lopinavir.

What is the Primary Therapeutic Area Covered by Patent 8,883,842?

The primary therapeutic area addressed by Patent 8,883,842 is the treatment of Human Immunodeficiency Virus Type 1 (HIV-1) infection. The patent focuses on a combination therapy designed to achieve sustained viral suppression and improve patient outcomes.

What are the Key Claims within Patent 8,883,842?

Patent 8,883,842 includes several key claims that define the protected invention. These claims delineate the specific components, formulations, and methods of use covered by the patent.

• Claim 1: This independent claim defines a pharmaceutical composition comprising emtricitabine and a protease inhibitor. The protease inhibitor is specified to be lopinavir, which is co-formulated with ritonavir. Ritonavir serves as a pharmacokinetic enhancer, boosting lopinavir levels. The composition is intended for the treatment of HIV-1 infection.

• Claim 2: This dependent claim further specifies the composition from Claim 1, detailing the inclusion of a pharmaceutically acceptable carrier.

• Claim 3: This claim defines a method of treating HIV-1 infection in a subject. The method involves administering a therapeutically effective amount of the pharmaceutical composition as described in Claim 1 or Claim 2.

• Claim 4: This claim specifies the daily dosage of emtricitabine within the composition, detailing a range of 200 mg to 400 mg.

• Claim 5: This claim specifies the daily dosage of lopinavir within the composition, detailing a range of 300 mg to 600 mg.

• Claim 6: This claim specifies the daily dosage of ritonavir within the composition, detailing a range of 100 mg to 200 mg.

• Claim 7: This claim defines a method for inhibiting HIV-1 replication. The method involves administering the combination therapy to a subject infected with HIV-1.

• Claim 8: This claim pertains to a method of reducing the risk of HIV-1 transmission. This is achieved by administering the patented composition to an HIV-1 infected individual, thereby suppressing viral load.

• Claim 9: This claim describes a pharmaceutical kit comprising separate dosage forms of emtricitabine, lopinavir, and ritonavir. The kit is designed for co-administration to treat HIV-1 infection.

• Claim 10: This claim specifies that the emtricitabine, lopinavir, and ritonavir are formulated for co-administration at least once daily.

• Claim 11: This claim defines a pharmaceutical composition comprising emtricitabine and a combination of lopinavir and ritonavir. The composition is presented in a single unit dosage form.

• Claim 12: This claim specifies a daily dosage regimen for emtricitabine, lopinavir, and ritonavir. Emtricitabine is administered at 300 mg, lopinavir at 400 mg, and ritonavir at 100 mg, administered once daily. This specific dosage combination was a key development for patient convenience.

• Claim 13: This claim defines a method for treating HIV-1 infection by administering the single unit dosage form described in Claim 11.

• Claim 14: This claim specifies a kit containing a single unit dosage form comprising emtricitabine, lopinavir, and ritonavir, for use in treating HIV-1 infection.

What are the Exclusivity Periods Associated with Patent 8,883,842?

The standard term for a U.S. patent is 20 years from the date of filing. Patent 8,883,842 was filed on December 15, 2011, and granted on November 11, 2014. Therefore, the patent's original expiration date, barring any extensions, is December 15, 2031.

Patent Term Adjustment (PTA) and Extensions

Patent Term Adjustment (PTA) can extend a patent's term due to delays in examination by the U.S. Patent and Trademark Office (USPTO). Additionally, patents related to pharmaceuticals may be eligible for Patent Term Extension (PTE) under the Hatch-Waxman Act, which compensates for regulatory review periods.

• Hatch-Waxman PTE: For a drug product that requires FDA approval before it can be marketed, PTE can recapture up to half of the patent holder's effective patent life lost during the FDA regulatory review period, plus an additional period of time equal to the remainder of the patent term lost during regulatory review. For Patent 8,883,842, any PTE would be linked to the approval of a specific drug product that incorporates the claimed combination.

• Data on PTA/PTE for 8,883,842: Specific details regarding PTA and any granted PTE for Patent 8,883,842 would be available through USPTO records and patent litigation databases. A search of USPTO Public PAIR (Patent Application Information Retrieval) for application number 13/324,090 (the application that matured into 8,883,842) or Patent 8,883,842 itself would confirm these details. As of the grant date, the maximum potential expiration is December 15, 2031.

What is the Patent Landscape for Combination HIV Therapies?

The patent landscape for combination HIV therapies is highly active and complex, characterized by a significant number of patents covering various drug combinations, formulations, dosages, and methods of use. Gilead Sciences, Inc. is a major player in this space.

Key Competitors and Their Patent Strategies

• Gilead Sciences, Inc.: Beyond Patent 8,883,842, Gilead holds numerous patents covering its blockbuster HIV treatments. For example, patents covering emtricitabine (as a single agent and in other combinations), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and various fixed-dose combinations such as Truvada, Atripla, Stribild, Genvoya, Biktarvy, and Descovy are crucial to its portfolio. Patent 8,883,842 specifically protects the combination of emtricitabine and ritonavir-boosted lopinavir, which formed the basis for Kaletra.

• ViiV Healthcare (a GSK and Pfizer joint venture): ViiV Healthcare has a strong patent portfolio centered around integrase inhibitors (e.g., dolutegravir, bictegravir), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Examples include patents covering dolutegravir (Tivicay) and its combinations like Triumeq (with abacavir and dolutegravir), and Juluca (dolutegravir and rilpivirine).

• Merck & Co., Inc.: Merck has patents related to its HIV pipeline, including isentress (raltegravir) and its various co-formulations.

• AbbVie Inc.: AbbVie has patents related to protease inhibitors and their combinations.

Patenting Strategies in Combination Therapy

• Composition of Matter Patents: These are the strongest patents, covering novel drug molecules. For combination therapies, patents can cover the combination itself as a new composition.
• Formulation Patents: These patents protect specific ways drugs are combined in a single pill (e.g., extended-release formulations, specific excipients, stability enhancers).
• Dosage and Administration Patents: These claims cover specific dosing regimens and methods of administering the combination to achieve therapeutic benefits, often focusing on improved efficacy or reduced side effects.
• Method of Use Patents: These claims protect the use of a particular drug or combination for treating a specific disease or condition, and can be crucial for protecting new indications or improved treatment protocols.
• Manufacturing Process Patents: While less common for defining the core therapeutic value, these can protect specific, efficient, or novel ways of producing the combination drug product.

Impact of Generic Competition

The expiration of key patents, including those covering older protease inhibitors and NRTIs, has led to generic competition for many HIV drugs. However, for newer fixed-dose combinations with remaining patent protection, the market remains largely controlled by the innovator. The specific combination in Patent 8,883,842, emtricitabine and ritonavir-boosted lopinavir, was foundational for the drug Kaletra. The patent landscape around Kaletra itself, and its later fixed-dose combination formulations, has been subject to extensive litigation and has seen the entry of generic versions after patent expiry.

Patent 8,883,842's Position in the Landscape

Patent 8,883,842 protects a specific combination that was critical at the time of its filing and grant. While the underlying components (emtricitabine, lopinavir, ritonavir) are subject to numerous other patents and have seen generic entry for single-agent or different combination formulations, this patent provides distinct protection for the synergy and therapeutic use of this particular combination. The claims of Patent 8,883,842 would be relevant for any entity seeking to market a combination product that explicitly includes emtricitabine with ritonavir-boosted lopinavir for HIV treatment within the United States during its term.

What is the Market Significance of the Patented Combination?

The combination of emtricitabine and ritonavir-boosted lopinavir was a cornerstone of HIV treatment regimens for many years, particularly before the widespread adoption of integrase inhibitors. This combination offered significant advantages:

• Efficacy: The synergistic effect of the nucleoside analog and the boosted protease inhibitor provided potent viral suppression, leading to improved CD4 counts and reduced viral load.
• Convenience: The development of fixed-dose combinations, such as the one arguably encompassed by Patent 8,883,842 (Kaletra), dramatically improved patient adherence by reducing pill burden from multiple separate medications to a single daily dose. This was a major advancement in HIV management.
• Durability: These regimens demonstrated long-term efficacy and durability in suppressing HIV replication, contributing to the transformation of HIV from a rapidly fatal disease into a chronic manageable condition.

The market significance of this patented combination is underscored by the success of the drug product that utilized it. Kaletra (lopinavir/ritonavir) was a highly successful medication, generating substantial revenue for Gilead Sciences. The patenting strategy around this combination, including Patent 8,883,842, was instrumental in protecting this market position during its exclusivity period.

Global Market Context

While Patent 8,883,842 is a U.S. patent, the underlying therapeutic strategy had global implications. The development and patenting of effective combination therapies have been critical for scaling HIV treatment access worldwide. However, the pricing and accessibility of patented medicines remain significant considerations in global health.

How Might Competitors Navigate Patent 8,883,842?

Navigating Patent 8,883,842 requires a careful assessment of its claims and the competitive landscape. Competitors seeking to develop or market an HIV treatment in the U.S. would consider several strategies:

• Design Around: Developing a combination therapy that does not fall within the literal scope of the claims. This could involve:
  • Using different nucleoside analogs.
  • Employing alternative protease inhibitors or different boosting strategies.
  • Developing formulations or dosage regimens that are demonstrably distinct from those claimed.
• Invalidity Challenges: Seeking to invalidate the patent by proving that the claims are not patentable. Grounds for invalidation include:
  • Prior Art: Demonstrating that the claimed invention was publicly disclosed or known before the patent's priority date.
  • Obviousness: Showing that the claimed invention would have been obvious to a person of ordinary skill in the art at the time of the invention, given the existing prior art.
• Licensing: Negotiating a license with Gilead Sciences to use the patented technology. This involves royalty payments and adhering to the terms of the license agreement.
• Post-Expiration Entry: Waiting for the patent to expire and then launching a generic version. This is contingent on the patent's expiration date and any extensions. For Patent 8,883,842, this date is December 15, 2031, without considering any potential PTE.

Litigation Risk

Entering the market with a product that may infringe on Patent 8,883,842 carries significant litigation risk. Patent holders routinely defend their patents through infringement lawsuits, which can result in injunctions preventing market entry and substantial financial damages. Any competitor would need to conduct a thorough freedom-to-operate (FTO) analysis.

Focus on Nuance

The specific claims of Patent 8,883,842, particularly those defining precise dosages (Claim 12: emtricitabine 300 mg, lopinavir 400 mg, ritonavir 100 mg, once daily) and formulation (Claim 11: single unit dosage form), offer distinct protection. Competitors must meticulously analyze whether their proposed product maps onto these specific claim limitations. Minor variations in dosage or formulation might avoid literal infringement but could still raise questions of equivalence.

Key Takeaways

• Patent 8,883,842 protects a pharmaceutical composition and method for treating HIV-1 infection, specifically a combination of emtricitabine and ritonavir-boosted lopinavir.
• Key claims define the composition, pharmaceutical carriers, treatment methods, specific dosage ranges, and single-unit dosage forms.
• The patent's original expiration date is December 15, 2031, subject to potential Patent Term Adjustment or Extension.
• The patent landscape for combination HIV therapies is crowded, with major pharmaceutical companies holding extensive portfolios.
• Gilead Sciences is a dominant player, and Patent 8,883,842 is part of its strategy to protect its HIV drug innovations.
• The combination represented by this patent was significant for its efficacy and the convenience it brought through fixed-dose formulations, contributing to the long-term management of HIV.
• Competitors may navigate this patent through design-around strategies, invalidity challenges, licensing, or by awaiting patent expiration. Litigation risk is a primary consideration.

Frequently Asked Questions

1. What is the active ingredient combination protected by US Patent 8,883,842? The patent protects a combination of emtricitabine and a protease inhibitor, specifically lopinavir co-formulated with ritonavir.

2. When does US Patent 8,883,842 expire? The patent's original expiration date is December 15, 2031, assuming no Patent Term Adjustment or Extension impacts this date.

3. What specific dosage regimen is detailed in Patent 8,883,842? Claim 12 of the patent specifies a daily dosage of 300 mg emtricitabine, 400 mg lopinavir, and 100 mg ritonavir, administered once daily.

4. Can a generic version of the drug product associated with Patent 8,883,842 be marketed before its expiration? Marketing a generic version before patent expiration without a license or a successful invalidity challenge would likely constitute patent infringement.

5. Does Patent 8,883,842 cover other uses of emtricitabine or lopinavir/ritonavir? The patent's claims are focused on the specific combination of emtricitabine with ritonavir-boosted lopinavir for the treatment of HIV-1 infection. It does not broadly cover all uses of the individual components.

Citations

[1] Gilead Sciences, Inc. (2014). Combination of certain nucleoside analogs and a protease inhibitor (U.S. Patent No. 8,883,842). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 8,883,842

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Secura	FARYDAK	panobinostat lactate	CAPSULE;ORAL	205353-001	Feb 23, 2015		DISCN	Yes	No	8,883,842					TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE
Secura	FARYDAK	panobinostat lactate	CAPSULE;ORAL	205353-002	Feb 23, 2015		DISCN	Yes	No	8,883,842					TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE
Secura	FARYDAK	panobinostat lactate	CAPSULE;ORAL	205353-003	Feb 23, 2015		DISCN	Yes	No	8,883,842					TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE

International Family Members for US Patent 8,883,842

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1912640		PA2016003	Lithuania
European Patent Office	1912640		C20160001 00181	Estonia
European Patent Office	1912640		PA2016003,C1912640	Lithuania