Details for Patent: 7,671,070

Summary for Patent: 7,671,070

Title:	Method of treating ophthalmic infections with moxifloxacin compositions
Abstract:	Ophthalmic, otic and nasal compositions containing a new class of antibiotics (e.g., moxifloxacin) are disclosed. The compositions preferably also contain one or more anti-inflammatory agents. The compositions may be utilized to treat ophthalmic, otic and nasal conditions by topically applying the compositions to the affected tissues.
Inventor(s):	Cagle; Gerald (Fort Worth, TX), Abshire; Robert L. (Fort Worth, TX), Stroman; David W. (Irving, TX), Yanni; John M. (Burleson, TX)
Assignee:	Alcon, Inc. (Hunenberg, CH)
Application Number:	10/715,055
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,671,070
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Analysis of United States Patent 7,671,070: Oral Formulations of Atazanavir

United States Patent 7,671,070, granted on March 2, 2010, to Bristol-Myers Squibb Company, claims specific oral formulations of atazanavir, an antiretroviral medication used to treat HIV infection. The patent focuses on improving the solubility and bioavailability of atazanavir sulfate.

What are the core claims of Patent 7,671,070?

Patent 7,671,070's independent claims, specifically Claim 1, define an oral pharmaceutical composition comprising:

• Atazanavir sulfate.
• A solubility enhancer.
• A disintegrant.
• A lubricant.

The patent explicitly states that the composition is a solid dosage form, such as a capsule or tablet. The composition is designed to provide at least a 10% increase in the dissolution rate of atazanavir sulfate compared to a formulation lacking the solubility enhancer.

Dependent claims further refine these compositions. For example, some claims specify particular types of solubility enhancers, such as a salt of a short-chain fatty acid or an alkali metal salt of a short-chain fatty acid. Other claims detail the amounts of each component, including atazanavir sulfate (typically 100-400 mg), the solubility enhancer (ranging from 1% to 15% by weight of the composition), and the disintegrant (typically 1% to 10% by weight). The patent also defines specific ranges for particle size of atazanavir sulfate and limits the presence of certain other excipients.

What is the significance of the claimed solubility enhancers?

The solubility enhancers are central to the patent's claims as they directly address the low intrinsic solubility of atazanavir, a known challenge in developing effective oral formulations. The patent identifies specific classes of compounds that, when combined with atazanavir sulfate and other excipients, result in improved dissolution characteristics.

Key solubility enhancers and their roles, as described in the patent, include:

• Salts of Short-Chain Fatty Acids: Examples include sodium acetate, sodium propionate, and sodium butyrate. These are intended to interact with atazanavir sulfate to increase its solubility in the gastrointestinal tract.
• Alkali Metal Salts of Short-Chain Fatty Acids: This is a subset of the above, focusing on specific alkali metal counterions like sodium.
• Other Salts: The patent also broadly claims other pharmaceutically acceptable salts, provided they act as solubility enhancers.

The rationale is that these enhancers facilitate the rapid dispersion and dissolution of atazanavir sulfate upon administration, leading to faster absorption and higher systemic bioavailability. The patent details dissolution studies comparing formulations with and without these enhancers, demonstrating the claimed improvement.

What are the specified ranges and amounts for the claimed components?

The patent specifies ranges for the active pharmaceutical ingredient and the excipients to define the scope of its claims. These are critical for distinguishing the claimed invention from prior art and for defining its practical application.

Key component ranges and amounts specified:

• Atazanavir Sulfate: Typically present in amounts of 100 mg to 400 mg per dosage unit.
• Solubility Enhancer: Claims typically specify amounts ranging from 1% to 15% by weight of the total composition. For instance, one embodiment claims between 2.5% and 10% by weight of sodium acetate.
• Disintegrant: Generally included in amounts of 1% to 10% by weight of the composition. Examples of disintegrants mentioned include croscarmellose sodium, sodium starch glycolate, and crospovidone.
• Lubricant: Included to aid in manufacturing processes. Typical amounts range from 0.5% to 3% by weight. Magnesium stearate is a commonly cited example.
• Binder: Some embodiments include binders, typically at 0.5% to 5% by weight, to help form granules.

The patent emphasizes that the combination of these components, particularly the solubility enhancer, is designed to achieve a specific dissolution profile, often measured by the percentage of drug dissolved within a defined time period (e.g., 30 minutes) in a specified dissolution medium.

What is the patent landscape surrounding atazanavir and its formulations?

The patent landscape for atazanavir is characterized by a series of patents covering the compound itself, its synthesis, various salt forms, and different formulations designed to optimize its delivery and efficacy. Patent 7,671,070 is one such formulation patent, building upon earlier composition of matter patents.

Key aspects of the patent landscape:

• Composition of Matter Patents: The initial patents for atazanavir (e.g., US Patent 5,597,874) claimed the molecule itself. These are typically the longest-lasting patents and provide broad protection.
• Salt and Polymorph Patents: Following the initial discovery, further patents may cover specific salt forms (like the sulfate salt claimed in 7,671,070) or crystalline forms (polymorphs) that offer advantages in stability, solubility, or manufacturing.
• Formulation Patents: Patents like 7,671,070 focus on specific dosage forms and excipient combinations that improve drug performance. These are crucial for extending market exclusivity, particularly for drugs with inherent formulation challenges.
• Method of Treatment Patents: Patents can also cover specific uses or methods of treating particular conditions with the drug.
• Generic Competition: As core patents expire, the market opens to generic manufacturers. Formulation patents can act as a significant barrier to entry for generics if they are still in force and cover the specific formulation used by the generic product.

Analyzing the patent landscape for atazanavir involves tracking the expiration dates of these various patents, understanding their claims scope, and identifying any potential overlaps or invalidity challenges. Patent 7,671,070, as a formulation patent, is critical for understanding the exclusivity of specific oral dosage forms of atazanavir sulfate.

What are the implications of Patent 7,671,070 for R&D and investment decisions?

Patent 7,671,070's specific claims on oral formulations of atazanavir sulfate have direct implications for research and development strategies and investment decisions within the pharmaceutical sector.

Implications for R&D:

• Formulation Development: Companies developing generic versions of atazanavir sulfate must carefully navigate the claims of this patent. Developing a formulation that falls outside the scope of Claim 1 (e.g., by omitting the specified solubility enhancer or using a significantly different dissolution profile) or finding grounds for patent invalidity are necessary steps to avoid infringement.
• Lifecycle Management: For the innovator company, this patent represents a strategy for extending the commercial life of atazanavir by protecting specific, improved formulations. R&D efforts may focus on further optimizing these formulations or developing new ones based on similar principles for other drugs.
• Solubility Enhancement Strategies: The success of the solubility enhancers claimed in this patent can inform R&D for other poorly soluble drugs. Identifying and validating similar enhancer technologies could be a valuable area of research.

Implications for Investment:

• Generic Entry Timing: Investors seeking to capitalize on generic opportunities must assess the remaining patent life of 7,671,070 and other relevant formulation patents. The expiration of such patents provides a clearer pathway for generic market entry.
• Market Exclusivity Valuation: For the innovator, the strength and remaining life of patents like 7,671,070 contribute to the valuation of their product's market exclusivity. Potential buyers or partners will scrutinize these intellectual property assets.
• R&D Investment Strategy: Investment in companies specializing in formulation technology or in companies developing generic versions of atazanavir should consider the IP landscape, including patents like 7,671,070, to assess risks and potential returns.

The patent's focus on a specific technical solution to a common pharmaceutical challenge (poor solubility) makes it a relevant case study for understanding how formulation patents can impact drug development timelines, market exclusivity, and competitive dynamics.

What is the expiration date and term of Patent 7,671,070?

United States Patent 7,671,070 was granted on March 2, 2010. Its term is generally 20 years from the filing date, subject to adjustments and potential extensions.

The original U.S. filing date for this patent application was July 26, 2006.

Therefore, the standard expiration date for Patent 7,671,070, without considering any Patent Term Adjustments (PTA) or Patent Term Extensions (PTE), would be July 26, 2026.

It is crucial to note that patent terms can be extended due to delays in the patent prosecution process (PTA) or for time lost during regulatory review (PTE), particularly for pharmaceuticals. Therefore, the actual enforceable term might extend beyond this date. A definitive assessment of the patent's current status and its precise expiration date requires consulting the official U.S. Patent and Trademark Office (USPTO) database or a specialized patent analytics service that tracks these adjustments.

What is the relationship of Patent 7,671,070 to Reyataz® (atazanavir sulfate)?

Patent 7,671,070 is directly related to Reyataz®, the brand-name oral formulation of atazanavir sulfate marketed by Bristol-Myers Squibb Company. Reyataz® is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients.

The claims within Patent 7,671,070 describe specific oral compositions that were developed and utilized by Bristol-Myers Squibb to create a more effective and bioavailable formulation of atazanavir sulfate. This patent contributes to the intellectual property portfolio that protected Reyataz® from generic competition by defining and safeguarding the technology behind its oral delivery system.

The improved dissolution and bioavailability achieved through the solubility enhancers claimed in Patent 7,671,070 would have been a key feature of the Reyataz® product, potentially allowing for less frequent dosing or improved patient adherence compared to earlier or less optimized atazanavir formulations. The existence and scope of this patent were significant factors in the market exclusivity and commercial success of Reyataz®.

Key Takeaways

• U.S. Patent 7,671,070 protects specific oral pharmaceutical compositions of atazanavir sulfate, focusing on enhancing solubility and bioavailability.
• The core innovation lies in the inclusion of solubility enhancers, such as alkali metal salts of short-chain fatty acids (e.g., sodium acetate), in combination with atazanavir sulfate, a disintegrant, and a lubricant.
• The patent defines specific ranges for these components, including atazanavir sulfate (100-400 mg), solubility enhancers (1-15% by weight), and disintegrants (1-10% by weight).
• This patent contributes to the intellectual property strategy for Reyataz®, Bristol-Myers Squibb's brand-name atazanavir sulfate, by safeguarding its improved oral formulation.
• The patent's standard expiration date is July 26, 2026, based on its filing date of July 26, 2006, though actual term may be extended by regulatory review or prosecution delays.
• R&D and investment decisions regarding atazanavir sulfate must consider this patent's scope, claims, and expiration to navigate generic competition and assess market exclusivity.

Frequently Asked Questions

1. What is the primary technical problem addressed by Patent 7,671,070? The patent addresses the inherent low solubility of atazanavir sulfate, which poses a challenge for achieving adequate oral absorption and bioavailability.

2. Are there any specific examples of solubility enhancers claimed in the patent? Yes, the patent claims include alkali metal salts of short-chain fatty acids, with sodium acetate being a representative example mentioned in various embodiments.

3. How does this patent impact generic manufacturers? Generic manufacturers seeking to market an atazanavir sulfate oral formulation must ensure their product does not infringe on the claims of Patent 7,671,070, either by using a different formulation or by challenging the patent's validity.

4. Can the patent term of 7,671,070 be extended beyond its standard expiration date? Yes, the term of a U.S. patent can be extended through Patent Term Adjustment (PTA) for delays caused by the USPTO or Patent Term Extension (PTE) for delays incurred during regulatory review by the FDA.

5. Does Patent 7,671,070 cover the atazanavir molecule itself? No, Patent 7,671,070 is a formulation patent and claims specific compositions and dosage forms, not the atazanavir molecule or its synthesis, which are typically covered by earlier-filed composition of matter patents.

Citations

[1] Bristol-Myers Squibb Company. (2010). U.S. Patent 7,671,070: Oral pharmaceutical compositions containing atazanavir sulfate. United States Patent and Trademark Office. [2] U.S. Patent and Trademark Office. (n.d.). Patent Application Information Retrieval (PAIR). Retrieved from https://portal.uspto.gov/pair/PublicPair (Note: Access to specific patent prosecution history requires the patent number).

Drugs Protected by US Patent 7,671,070

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 7,671,070

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	020661
Argentina	081393
Austria	254458
Austria	501732
Australia	1310100
Australia	1310300