Details for Patent: 5,922,695

Summary for Patent: 5,922,695

Title:	Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
Abstract:	Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR.sup.3. The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly to patients for antiviral therapy or prophylaxis. Embodiments are particularly useful when administered orally.
Inventor(s):	Arimilli; Murty N. (Fremont, CA), Cundy; Kenneth C. (Belmont, CA), Dougherty; Joseph P. (New York, NY), Kim; Choung U. (San Carlos, CA), Oliyai; Reza (Foster City, CA), Stella; Valentino J. (Lawrence, KS)
Assignee:	Gilead Sciences, Inc. (Foster City, CA)
Application Number:	08/900,746
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 5,922,695
Patent Claim Types: see list of patent claims	Compound; Use; Process;

United States Patent 5,922,695: A Detailed Analysis

Overview of the Patent

United States Patent 5,922,695, titled "Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability," is a crucial patent held by Gilead Sciences, Inc. This patent is one of the four key patents related to the drug tenofovir disoproxil fumarate (TDF), a significant medication in the treatment of HIV/AIDS.

Background and Context

The patent was granted to Gilead Sciences and relates to novel compounds that are esters of antiviral phosphonomethoxy nucleotide analogs. These compounds are designed to enhance the oral bioavailability of the antiviral agents, making them more effective in treating viral infections such as HIV/AIDS[4].

Scope and Claims

The patent 5,922,695 encompasses a range of claims that define the scope of the invention. Here are some key aspects:

Chemical Structure and Composition

The patent describes antiviral phosphonomethoxy nucleotide analogs, which are modified to include esters with carbonates and/or carbamates. These modifications are intended to improve the oral bioavailability of the compounds, making them more effective when taken orally[4].

Specific Compounds and Derivatives

The claims include various chemical groups and derivatives, such as alkyl, aryl, alkenyl, and alkynyl groups, which are part of the nucleotide analogs. The patent also specifies the use of certain chemical groups like isopropyl, tert-butyl, and cyano groups[4].

Pharmaceutical Applications

The primary application of these compounds is in the treatment of viral infections, particularly HIV/AIDS. The improved oral bioavailability enhances the therapeutic efficacy of the drug, making it a critical component in antiviral therapy[5].

Patent Landscape and Challenges

Reexamination Proceedings

In 2007, the Public Patent Foundation (PUBPAT) challenged the validity of this patent along with three other related patents (U.S. Patents No. 5,935,946, 5,977,089, and 6,043,230) by requesting reexaminations from the U.S. Patent and Trademark Office (USPTO). PUBPAT alleged that prior art existed which could have impacted the issuance of these patents[1][2][5].

USPTO Review and Outcome

The USPTO granted PUBPAT's requests for reexamination and initiated review proceedings. Following a detailed analysis, the USPTO confirmed the patentability of the first two patents, including U.S. Patent 5,922,695, with no reduction in the scope of the claims. This decision reinforced Gilead Sciences' confidence in the novelty and exclusivity of their product[1][2].

Impact on HIV/AIDS Treatment

Exclusive Rights and Market Dominance

The confirmation of these patents by the USPTO allowed Gilead Sciences to maintain exclusive rights to distribute TDF in the United States. This exclusivity has significant implications for the cost and accessibility of the drug, as it prevents other companies from manufacturing and distributing generic versions of TDF[5].

Global Implications

Gilead Sciences has also applied for similar patents in other countries, including India, where they have faced opposition from non-profit AIDS patient groups. The global patent landscape for TDF is complex, with ongoing challenges and debates about patent validity and public health implications[5].

Public Health and Access to Medication

Criticism and Advocacy

Organizations like PUBPAT argue that undeserved patents can lead to exorbitant prices for life-saving medications, hindering access to treatment for millions of people worldwide. The challenge to these patents is part of a broader effort to ensure that patients have access to the best medical treatments available without unjustified impediments[5].

Forward-Looking Statements and Risks

Gilead Sciences has acknowledged the risks associated with patent challenges, including the possibility that the USPTO may narrow or invalidate some or all of the original claims. These risks could impact the company's ability to maintain its exclusive position in the market and affect the availability and cost of TDF[1].

Key Takeaways

• Patent Scope: U.S. Patent 5,922,695 covers antiviral phosphonomethoxy nucleotide analogs with improved oral bioavailability.
• Challenges: The patent was challenged by PUBPAT due to alleged prior art, but the USPTO confirmed its validity.
• Impact on Treatment: The patent's confirmation maintains Gilead Sciences' exclusive rights to TDF, affecting its cost and accessibility.
• Global Implications: Similar patents are being contested globally, particularly in regions with high HIV/AIDS prevalence.
• Public Health: The debate surrounding these patents highlights the tension between patent protection and public health access to essential medications.

FAQs

Q: What is the main subject of U.S. Patent 5,922,695? A: The patent covers antiviral phosphonomethoxy nucleotide analogs with improved oral bioavailability, specifically related to the drug tenofovir disoproxil fumarate (TDF).

Q: Who challenged the validity of this patent? A: The Public Patent Foundation (PUBPAT) challenged the validity of this patent along with three other related patents held by Gilead Sciences.

Q: What was the outcome of the USPTO review? A: The USPTO confirmed the patentability of U.S. Patent 5,922,695 with no reduction in the scope of the claims.

Q: How does this patent affect the treatment of HIV/AIDS? A: The patent's confirmation allows Gilead Sciences to maintain exclusive rights to distribute TDF, impacting its cost and accessibility for patients.

Q: Are there global implications for this patent? A: Yes, Gilead Sciences has applied for similar patents in other countries, facing opposition from non-profit groups, particularly in regions with high HIV/AIDS prevalence.

Cited Sources

1. Gilead Sciences Press Release: "U.S. Patent Office Confirms First of Four Viread(R) Patents"[1]
2. Gilead Sciences Press Release: "U.S. Patent Office Confirms Second of Four Viread(R) Patents"[2]
3. USPTO Notices: "Patent and Trademark Office Notices"[3]
4. Google Patents: "US5922695A - Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability"[4]
5. Community Catalyst: "PAL member Public Patent Foundation challenges Gilead HIV/AIDS drug patents"[5]

Drugs Protected by US Patent 5,922,695

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,922,695

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0915894		CA 2005 00032	Denmark
European Patent Office	0915894		91178	Luxembourg
European Patent Office	0915894		05C0032	France
European Patent Office	0915894		CA 2008 00023	Denmark
European Patent Office	0915894		91433	Luxembourg