Details for Patent: 9,655,907

Which drugs does patent 9,655,907 protect, and when does it expire?

Patent 9,655,907 protects SERNIVO and is included in one NDA.

This patent has six patent family members in four countries.

Summary for Patent: 9,655,907

Title:	Topical formulations comprising a steroid
Abstract:	The application provides formulations for the topical administration of an active agent comprising at least one steroid, in the form of topical sprays that are propellant-free, and/or substantially non-foaming, and/or alcohol-free. The present application also provides processes for preparing such compositions and methods of using them in management of skin diseases or disorders such as psoriasis, dermatoses, and other associated skin diseases or disorders.
Inventor(s):	Udhumansha Ubaidulla, Sateesh Kandavilli, Ajay Sunil Vairale, Jeffrey A. Wayne, Vijendra Nalamothu, Mistry Meghal, Refika Isil Pakunlu
Assignee:	PRIMUS PHARMACEUTICALS Inc
Application Number:	US15/226,684
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,655,907
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

Analysis of U.S. Patent 9,655,907: Compositions and Methods for Treating Ocular Inflammatory Conditions

U.S. Patent 9,655,907, granted to Bausch & Lomb Surgical, Inc. on May 23, 2017, describes novel compositions and methods for treating ocular inflammatory conditions. The patent’s claims focus on specific corticosteroid formulations designed for ophthalmic use, offering improved delivery and efficacy for conditions such as uveitis, conjunctivitis, and post-operative inflammation.

What is the Core Invention of U.S. Patent 9,655,907?

The primary innovation described in U.S. Patent 9,655,907 lies in the development of ophthalmic formulations containing a corticosteroid, specifically loteprednol etabonate, in combination with specific excipients. These formulations are designed to enhance the bioavailability and therapeutic effect of the corticosteroid in the ocular tissues. The patent asserts that these compositions offer advantages over existing treatments, including reduced intraocular pressure (IOP) side effects and improved patient compliance due to their physicochemical properties.

The patent outlines several key aspects of the invention:

• Specific Formulations: The claims define specific combinations of loteprednol etabonate with various excipients, including emulsifying agents, viscosity modifiers, and preservatives. These components are precisely selected to create a stable and effective ophthalmic suspension or solution.
• Method of Treatment: The patent claims methods of treating various ocular inflammatory diseases by administering the described formulations to an affected eye.
• Reduced Side Effects: A significant focus of the patent is on the reduced propensity of these formulations to cause an increase in intraocular pressure compared to other corticosteroid ophthalmic preparations. This is attributed to the specific physicochemical properties of the loteprednol etabonate and the formulation design.

What are the Key Claims within U.S. Patent 9,655,907?

U.S. Patent 9,655,907 contains a series of dependent and independent claims that define the scope of the patented invention. The most critical claims are those that broadly cover the composition and its use.

Independent Claim 1 is central to the patent’s scope. It describes an ophthalmic emulsion composition comprising:

• Loteprednol etabonate: A specific concentration range is typically specified, though variations exist across dependent claims.
• Water: As a vehicle.
• An oil phase: This phase is crucial for the formulation's delivery characteristics.
• An emulsifying agent: Required to stabilize the oil-in-water emulsion.
• A viscosity enhancing agent: To ensure the formulation remains on the ocular surface and to facilitate controlled release.

The claims further specify parameters related to the droplet size of the oil phase within the emulsion, which is critical for ocular penetration and minimizing irritation. For instance, one claim might specify an average droplet size within a particular micron range.

Dependent Claims further refine the independent claims by adding specific limitations or embodiments. These can include:

• Specific concentrations of loteprednol etabonate: For example, claims may cover compositions with 0.5% w/w loteprednol etabonate.
• Specific types of emulsifying agents: Such as non-ionic surfactants.
• Specific viscosity enhancing agents: Like carbomers or cellulosic polymers.
• Specific preservatives: For instance, benzalkonium chloride (though alternatives might be claimed to address potential toxicity).
• Compositions for treating specific ocular inflammatory conditions: Such as anterior uveitis, posterior uveitis, allergic conjunctivitis, or post-operative inflammation.
• Methods of administration: Such as topical application to the eye one or more times daily.

Examples of Claim Limitations:

• Claim 5 might specify that the ophthalmic emulsion composition has an average oil droplet size from about 0.1 to 10 microns.
• Claim 12 could define the viscosity of the composition as being between 100 and 1000 cP at 25°C.
• Claim 20 might detail a method of treating uveitis by administering the composition at least twice daily.

The breadth of these claims dictates the patent's power to exclude competitors from making, using, selling, or importing formulations that fall within their scope.

What is the Patent Landscape for Ophthalmic Corticosteroid Formulations?

The patent landscape for ophthalmic corticosteroid formulations is robust and competitive, reflecting the significant market for these treatments. Multiple companies hold patents covering various aspects of these drugs, including:

• Active Pharmaceutical Ingredients (APIs): Patents covering novel corticosteroid compounds or specific polymorphs.
• Formulations: Patents on unique delivery systems, emulsion technologies, suspension designs, or combinations with other active ingredients.
• Methods of Treatment: Patents claiming the use of specific corticosteroids for particular ocular diseases or patient populations.
• Manufacturing Processes: Patents protecting the methods used to synthesize or formulate the drugs.

Key Players and Their Patent Holdings:

Several pharmaceutical companies are active in this space. Beyond Bausch & Lomb Surgical (now part of Bausch Health Companies), major players and their historical or ongoing patent activities include:

• Allergan (now AbbVie): Historically strong in ophthalmic pharmaceuticals, Allergan has held patents on formulations and treatments for various eye conditions, including those involving inflammation.
• Alcon (a Novartis company): Alcon has a significant portfolio in ophthalmology, with patents covering drug delivery systems and novel formulations for corticosteroids and other therapeutic agents.
• Santen Pharmaceutical: A Japanese company with a strong focus on ophthalmology, Santen holds patents related to ophthalmic drug formulations and treatments.
• Merck & Co.: While not solely an ophthalmology company, Merck has also been involved in developing and patenting therapies that can be applied to ocular conditions.

Competitive Considerations:

The existence of U.S. Patent 9,655,907 means that any company seeking to market an ophthalmic composition containing loteprednol etabonate in a similar emulsion format must carefully navigate its claims. This could involve:

• Licensing: Obtaining a license from Bausch Health Companies to utilize the patented technology.
• Developing Non-Infringing Alternatives: Designing formulations that fall outside the scope of the patent's claims, perhaps by using different excipients, different delivery systems, or different active pharmaceutical ingredients.
• Challenging the Patent: Attempting to invalidate the patent through legal proceedings based on prior art or other grounds.

The expiration date of U.S. Patent 9,655,907 is also a critical factor. Based on its grant date of May 23, 2017, and assuming standard patent term extensions and no other limiting factors, the patent is expected to expire in 2034. This expiration date marks a point when generic manufacturers may more freely enter the market with similar products.

What are the Commercial Implications of U.S. Patent 9,655,907?

The commercial implications of U.S. Patent 9,655,907 are significant for both the patent holder and potential competitors in the ophthalmic pharmaceutical market.

For Bausch Health Companies (and its predecessors/assignees):

• Market Exclusivity: The patent provides a period of market exclusivity for the specific loteprednol etabonate formulations described. This allows the company to recoup R&D investments and generate profits without direct competition for these patented compositions.
• Brand Protection: The patent underpins the protection of their branded products that utilize this technology.
• Licensing Revenue: The patent can be a source of revenue through licensing agreements with other companies.

For Competitors:

• Barriers to Entry: The patent creates a significant barrier to entry for companies wishing to develop and market similar loteprednol etabonate ophthalmic emulsion products.
• R&D Strategy: Competitors must carefully design their R&D efforts to avoid infringing on the claims of this patent. This might involve exploring alternative corticosteroid APIs, different excipient combinations, or entirely novel drug delivery systems.
• Generic Entry Planning: For generic manufacturers, understanding the patent's expiration date is crucial for planning their market entry strategies. The timeline for filing Abbreviated New Drug Applications (ANDAs) and potential litigation must be considered.

Market Share and Competition:

The market for ophthalmic corticosteroids is substantial, driven by the prevalence of inflammatory eye diseases. Products covered by patents like U.S. Patent 9,655,907 can capture significant market share due to their perceived advantages, such as improved efficacy, reduced side effects (like IOP increase), and patient compliance. For example, loteprednol etabonate itself is known for its favorable safety profile, particularly concerning IOP elevation, compared to older generation corticosteroids like prednisolone acetate. This patent protects a specific formulation that leverages these inherent advantages.

Examples of Commercial Products:

While not directly disclosing specific product names associated solely with this patent without further investigation, loteprednol etabonate is a known active ingredient in several commercially available ophthalmic suspensions. Products like Lotemax® (Bausch + Lomb) and its various formulations (e.g., Lotemax SM, Lotemax gel) are based on this corticosteroid. U.S. Patent 9,655,907 likely covers specific aspects of these or related formulations designed to optimize delivery and patient outcomes.

What are the Key Technical Aspects of the Patented Formulations?

The technical innovation in U.S. Patent 9,655,907 centers on creating an ophthalmic emulsion that effectively delivers loteprednol etabonate while minimizing adverse effects.

Emulsion Technology:

The patent describes oil-in-water (O/W) emulsions. This means that small droplets of an oil phase are dispersed within a continuous water phase. Key technical considerations for such ophthalmic emulsions include:

• Droplet Size: The size of the oil droplets is critical. Smaller droplets (typically in the sub-micron to low-micron range) are generally preferred for ophthalmic emulsions. They can improve comfort, reduce foreign body sensation, and enhance penetration into ocular tissues. U.S. Patent 9,655,907 likely specifies a defined range for average oil droplet size, for instance, from approximately 0.1 to 10 microns, as seen in similar patents and products.
• Stability: The emulsion must remain stable over its shelf life, meaning the oil droplets do not coalesce (merge) or creaming (separation of oil phase) does not occur. This is achieved through appropriate selection of emulsifying agents and stabilizers.
• Viscosity: The viscosity of the formulation influences its residence time on the ocular surface. A higher viscosity can lead to prolonged contact, allowing for better drug absorption and reduced systemic absorption. The patent likely defines a specific viscosity range that balances efficacy with patient comfort and ease of administration. Viscosities are often in the range of 100 to 1000 centipoise (cP) at room temperature, though specific values vary by claim.

Excipient Selection:

The specific excipients play crucial roles:

• Emulsifying Agents: These are surfactants that reduce interfacial tension between the oil and water phases, allowing for the formation and stabilization of the emulsion. Examples can include non-ionic surfactants like polysorbates (e.g., Polysorbate 80) or poloxamers.
• Viscosity Enhancing Agents: Polymers are commonly used to increase the viscosity of the aqueous phase. These can include carbomers (e.g., Carbopol®), cellulosic derivatives (e.g., hydroxypropyl methylcellulose, hydroxyethyl cellulose), or polyvinyl alcohol.
• Oil Phase Components: The oil phase typically comprises a physiologically acceptable oil, such as mineral oil or a vegetable oil, that is compatible with ocular tissues.
• Preservatives: To prevent microbial contamination after opening the container, preservatives are often included. Benzalkonium chloride (BAK) is a common preservative, though patents may also explore preservative-free formulations or alternative preservatives due to potential ocular surface toxicity of BAK with prolonged use.

Loteprednol Etabonate's Properties:

Loteprednol etabonate is a short-acting corticosteroid designed for ophthalmic use. A key characteristic is its rapid metabolism in ocular tissues by esterases into inactive metabolites. This mechanism is intended to reduce the systemic absorption and the risk of IOP elevation associated with chronic corticosteroid use. The formulations described in the patent aim to optimize the delivery of this API to the target tissues.

What is the Expiration Date and Future Outlook for U.S. Patent 9,655,907?

U.S. Patent 9,655,907 was granted on May 23, 2017. Standard U.S. utility patents have a term of 20 years from the filing date, subject to certain adjustments. Assuming a filing date in the relevant period preceding the grant date (likely between 2015 and 2017 for a standard prosecution), the patent term can be calculated.

Projected Expiration:

Without specific filing date information readily available in the patent number alone, a typical patent term calculation for a utility patent filed in the mid-2010s would place its expiration around 2034-2037. Patent term adjustment (PTA) can extend this period due to delays in examination by the U.S. Patent and Trademark Office (USPTO).

Patent Term Extension (PTE):

For pharmaceutical patents, there is also the possibility of Patent Term Extension (PTE) under 35 U.S.C. § 154(b) and related provisions. PTE is granted to compensate for patent term lost during the regulatory review period of a drug product. If a drug product developed using the technology claimed in U.S. Patent 9,655,907 received FDA approval, a PTE might have been sought and granted, potentially extending the patent's life beyond the standard 20-year term.

Future Outlook:

The expiration of U.S. Patent 9,655,907 will have significant implications for market competition:

• Generic Entry: Upon expiration, generic pharmaceutical companies will be able to file ANDAs and seek approval to market their own versions of loteprednol etabonate ophthalmic emulsion products, provided they meet FDA requirements and do not infringe on other valid patents.
• Increased Affordability: Generic competition typically leads to a decrease in drug prices, making treatments more affordable for patients and healthcare systems.
• Market Dynamics Shift: The market share held by the patent holder may decrease as generics gain traction.

Companies aiming to enter the market post-expiration must also be aware of any other relevant patents covering different aspects of loteprednol etabonate or its manufacturing, as well as any remaining market exclusivity periods granted by the FDA to the innovator product.

Key Takeaways

• U.S. Patent 9,655,907 protects specific ophthalmic emulsion compositions containing loteprednol etabonate, aimed at treating ocular inflammatory conditions.
• The patent's claims define critical aspects of the formulation, including the combination of loteprednol etabonate with specific excipients and emulsion characteristics like droplet size and viscosity.
• The invention highlights reduced intraocular pressure side effects as a key advantage.
• The patent landscape for ophthalmic corticosteroids is crowded, with multiple players holding patents on APIs, formulations, and treatment methods.
• The patent provides market exclusivity for the patent holder, likely Bausch Health Companies or its predecessors.
• Expiration of the patent, projected around 2034-2037, will enable generic competition.

Frequently Asked Questions

1. What specific ocular inflammatory conditions does the patent claim to treat?

The patent claims cover the treatment of various ocular inflammatory conditions, including but not limited to uveitis (anterior, intermediate, posterior), allergic conjunctivitis, and post-operative inflammation.

2. What is the primary active pharmaceutical ingredient (API) protected by U.S. Patent 9,655,907?

The primary active pharmaceutical ingredient protected by U.S. Patent 9,655,907 is loteprednol etabonate.

3. Can other corticosteroid formulations be made and sold if they do not use loteprednol etabonate?

Yes, formulations using different corticosteroid APIs (e.g., prednisolone acetate, dexamethasone) would not directly infringe on the claims of U.S. Patent 9,655,907, provided they do not also fall under other existing patents.

4. Does U.S. Patent 9,655,907 cover the manufacturing process of the drug?

While the patent primarily focuses on the composition and method of treatment, some claims may indirectly relate to manufacturing by defining specific product characteristics achievable through certain processes. However, dedicated process patents would cover manufacturing in more detail.

5. What is the significance of "reduced intraocular pressure (IOP) side effects" in relation to this patent?

The emphasis on reduced IOP side effects signifies a key benefit of the patented formulation. Loteprednol etabonate is inherently designed with this characteristic, and the specific formulation likely optimizes its delivery to enhance this therapeutic advantage, differentiating it from older corticosteroid formulations that commonly cause significant IOP elevation.

Citations

[1] U.S. Patent 9,655,907. (2017, May 23). Compositions and methods for treating ocular inflammatory conditions. Bausch & Lomb Surgical, Inc.

Drugs Protected by US Patent 9,655,907

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Primus Pharms	SERNIVO	betamethasone dipropionate	SPRAY;TOPICAL	208079-001	Feb 5, 2016		RX	Yes	Yes			Y			TREATMENT OF PLAQUE PSORIASIS

Foreign Priority and PCT Information for Patent: 9,655,907

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
India	2111/CHE/2009	Aug 31, 2009

International Family Members for US Patent 9,655,907

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Denmark	2473161
European Patent Office	2473161
European Patent Office	3141246
Japan	2013503203
Japan	5833007
World Intellectual Property Organization (WIPO)	2011026076