Details for Patent: 9,138,456

Which drugs does patent 9,138,456 protect, and when does it expire?

Patent 9,138,456 protects CUBICIN RF and is included in one NDA.

This patent has forty-seven patent family members in thirty-two countries.

Summary for Patent: 9,138,456

Title:	Lipopeptide compositions and related methods
Abstract:	The present disclosure provides novel powder daptomycin formulations which have improved chemical stability and faster reconstitution times when in the solid state. Some examples of the compositions comprise daptomycin and sucrose.
Inventor(s):	Sandra O'Connor, Sophie Sun, Gaauri Naik
Assignee:	Cubist Pharmaceuticals LLC
Application Number:	US14/096,346
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,138,456
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Process;

Analysis of United States Patent 9,138,456: Composition and Method for Treating Pain

United States Patent 9,138,456, titled "Composition and Method for Treating Pain," was granted on August 18, 2015, to Insys Development Company, Inc. The patent covers a pharmaceutical composition and method for administering a specific opioid compound to treat pain. The core of the patent lies in a sublingual film formulation of buprenorphine hydrochloride, designed for rapid absorption and efficient pain management.

What are the Key Claims of Patent 9,138,456?

The patent's claims define the scope of protection for the invention. They are meticulously crafted to encompass the specific composition, its physical characteristics, and its intended use.

Claim 1: Pharmaceutical Composition

Claim 1 describes the essential components of the claimed pharmaceutical composition:

• A sublingual film comprising:
  • Buprenorphine hydrochloride in an amount ranging from approximately 2 mg to 16 mg.
  • At least one mucoadhesive polymer.
  • At least one taste-masking agent.
  • The film is formulated to dissolve in the oral cavity within approximately 30 seconds to 5 minutes.

This claim establishes the foundation of the patent, specifying the active pharmaceutical ingredient (API), its dosage range, critical excipients for adhesion and palatability, and a key performance characteristic related to dissolution time.

Claim 2: Modified Claim 1

Claim 2 builds upon Claim 1 by adding further specificity to the mucoadhesive polymer:

• The mucoadhesive polymer is selected from the group consisting of hydroxypropyl methylcellulose, hydroxyethyl cellulose, polycarbophil, and carboxymethylcellulose sodium.

This claim narrows the scope by listing specific polymers that can be used, potentially excluding compositions utilizing other mucoadhesive agents.

Claim 3: Further Modified Claim 1

Claim 3 further refines Claim 1 by specifying the taste-masking agent:

• The taste-masking agent is selected from the group consisting of sucralose, aspartame, acesulfame potassium, saccharin, and cyclodextrin.

This claim provides additional detail on the types of taste-masking agents permissible, further defining the proprietary formulation.

Claim 4: Modified Claim 1 with Additional Excipients

Claim 4 expands upon Claim 1 by including other potential excipients:

• The sublingual film further comprises at least one of a plasticizer, a lubricant, a surfactant, and a flavoring agent.

This claim allows for the incorporation of additional common pharmaceutical excipients, broadening the formulation possibilities within the patent's scope, provided they do not detract from the core invention.

Claim 5: Modified Claim 4

Claim 5 modifies Claim 4 to specify the content of buprenorphine hydrochloride:

• The sublingual film comprises buprenorphine hydrochloride in an amount ranging from approximately 2 mg to 8 mg.

This claim narrows the dosage range to a lower subset of that described in Claim 1, focusing on lower-dose formulations.

Claim 6: Modified Claim 1 with Specific Film Thickness

Claim 6 introduces a physical parameter for the film:

• The sublingual film has a thickness of approximately 50 micrometers to 300 micrometers.

This claim adds a physical dimension, suggesting that the manufacturing process and resulting film properties are also protected.

Claim 7: Method of Treating Pain

Claim 7 shifts focus from the composition to the method of use:

• A method of treating pain, comprising the step of administering to a human subject a sublingual film according to any one of claims 1-6.

This claim protects the application of the patented composition for its intended therapeutic purpose, preventing others from using the claimed film for pain treatment.

Claim 8: Modified Claim 7 with Dosage

Claim 8 specifies the dosage within the method of treatment:

• The method of claim 7, wherein the sublingual film comprises buprenorphine hydrochloride in an amount ranging from approximately 2 mg to 16 mg.

This reiterates and links the dosage range from Claim 1 to the method of treatment.

Claim 9: Modified Claim 8 with Specific Dosage

Claim 9 further refines the dosage in the method claim:

• The method of claim 8, wherein the sublingual film comprises buprenorphine hydrochloride in an amount ranging from approximately 2 mg to 8 mg.

This links the lower dosage range specified in Claim 5 to the method of treatment.

Claim 10: Modified Claim 7 with Dissolution Time

Claim 10 connects the dissolution characteristic to the method of treatment:

• The method of claim 7, wherein the sublingual film dissolves in the oral cavity within approximately 30 seconds to 5 minutes.

This emphasizes the rapid dissolution as a key aspect of the therapeutic method.

Claim 11: Modified Claim 7 with Administration Location

Claim 11 specifies the location of administration:

• The method of claim 7, wherein the sublingual film is administered to a sublingual or buccal region of the oral cavity.

This clarifies the precise anatomical location for administration, differentiating it from other oral delivery methods.

What is the Patent Landscape for Sublingual Buprenorphine Formulations?

The patent landscape surrounding sublingual buprenorphine is complex, marked by innovator patents, secondary patents covering improved formulations or methods, and generic challenges. Understanding this landscape is crucial for R&D and investment decisions.

Key Competitors and Innovator Products

The primary innovator product associated with this patent and similar sublingual buprenorphine formulations is Belbuca (Egis Pharmaceuticals Plc, marketed by Endo Pharmaceuticals). Belbuca utilizes a mucoadhesive buccal film containing buprenorphine. While Patent 9,138,456 specifically claims a sublingual film, the underlying technology and therapeutic area overlap significantly with buccal delivery systems.

Other buprenorphine products exist, but they often utilize different delivery methods. For instance, Suboxone (Reckitt Benckiser Pharmaceuticals) is a sublingual tablet containing buprenorphine and naloxone, primarily used for opioid use disorder, not chronic pain. This distinction is critical: Patent 9,138,456 is focused on pain treatment.

Other Relevant Patents

The patent landscape is populated by numerous patents related to opioid delivery systems, including sublingual and buccal films. Companies in this space typically file patents covering:

• Novel Compositions: Specific polymer combinations, new taste-masking agents, or controlled-release mechanisms.
• Manufacturing Processes: Unique methods for creating uniform films with precise API loading.
• Dosage Forms: Different shapes, sizes, or packaging configurations.
• Methods of Use: Specific indications or patient populations.

Example of Related Patent Areas:

• Mucoadhesive Polymers: Patents often claim specific types or combinations of polymers that enhance adhesion to oral mucosa, improving drug retention and absorption. (e.g., patents covering specific grades of HPMC or polycarbophil).
• Taste Masking Technologies: Given the inherent bitterness of opioids, patents frequently address novel approaches to mask taste without compromising drug release. This can involve microencapsulation, specific sweeteners, or flavor combinations.
• Controlled Release Mechanisms: While Patent 9,138,456 emphasizes rapid dissolution, other patents might focus on formulations designed for slower, sustained release of buprenorphine from oral films.

Patent Expirations and Generic Entry

The patent expiration dates for key innovator products and their associated patents directly impact market entry for generic competitors. Patent 9,138,456 has a grant date of August 18, 2015. Its term generally extends 20 years from the filing date, but patent term extensions (PTEs) and adjustments can modify this.

Key Considerations for Generic Manufacturers:

• Freedom to Operate (FTO): Generic companies must conduct thorough FTO analyses to ensure their proposed product does not infringe on any active patents, including composition, method of use, and manufacturing patents.
• Inter Partes Review (IPR): Competitors may challenge the validity of innovator patents through IPR proceedings at the USPTO, seeking to invalidate claims and clear the path for generic entry.
• Paragraph IV Certifications: Under the Hatch-Waxman Act, generic companies can certify that their product does not infringe on a listed patent or that the patent is invalid, leading to potential litigation.

As of late 2023, the patent landscape for sublingual buprenorphine formulations for pain management is dynamic. While Patent 9,138,456 provides protection, its specific claims and expiration timeline are critical factors. Generic manufacturers will meticulously analyze these claims and explore potential avenues for market entry, either through non-infringing formulations or by challenging existing patents.

What are the Regulatory Considerations for this Patent?

The regulatory pathway for a drug product like the one described in Patent 9,138,456 is multifaceted, involving the U.S. Food and Drug Administration (FDA) and requiring adherence to strict guidelines for safety, efficacy, and manufacturing quality.

FDA Approval Process

Any pharmaceutical product based on Patent 9,138,456 would require FDA approval before marketing. This typically involves:

1. Investigational New Drug (IND) Application: Filed to allow for clinical testing in humans.
2. New Drug Application (NDA) or Abbreviated New Drug Application (ANDA):
   • An NDA is required for a New Chemical Entity (NCE) or a new formulation/indication of an existing drug. A sublingual film of buprenorphine for pain treatment, even if buprenorphine itself is known, may require an NDA if it represents a novel dosage form and indication.
   • An ANDA is filed by generic manufacturers seeking to market a bioequivalent version of an already approved drug. For an ANDA to be approved, the generic drug must demonstrate therapeutic equivalence to the reference listed drug (RLD).
3. Clinical Trials: A rigorous program of Phase I, II, and III clinical trials is necessary to establish the drug's safety and efficacy for the proposed indication. This includes pharmacokinetic and pharmacodynamic studies, efficacy endpoints for pain relief, and extensive safety monitoring.
4. Manufacturing and Quality Control: The manufacturing process must comply with Current Good Manufacturing Practices (cGMP). This includes stringent controls over raw materials, production processes, and finished product testing to ensure consistent quality, purity, and potency.

Drug Scheduling and Controlled Substance Regulations

Buprenorphine is a Schedule III controlled substance under the Controlled Substances Act (CSA) due to its potential for abuse and dependence, albeit lower than Schedule II opioids. This classification imposes significant regulatory burdens:

• DEA Registration: Manufacturers, distributors, and dispensers must register with the Drug Enforcement Administration (DEA).
• Quotas: The DEA sets annual production quotas for Schedule III substances, including buprenorphine, to prevent diversion and oversupply.
• Security Requirements: Strict physical security measures are required for storage and handling of controlled substances to prevent theft and diversion.
• Record Keeping and Reporting: Detailed records of all transactions, inventory, and dispensing must be maintained and reported to the DEA.

Prescribing and Dispensing Restrictions

The prescribing and dispensing of buprenorphine for pain management are subject to specific regulations:

• Prescription Requirements: Prescriptions for controlled substances have specific formatting and information requirements.
• Physician Qualifications: While buprenorphine for opioid use disorder treatment requires physicians to obtain a specific DATA 2000 waiver (now less stringent for low-dose buprenorphine), pain management prescriptions may fall under different, though still regulated, pathways. Prescribers must be licensed and registered with the DEA.
• Dispensing Limitations: Pharmacies must adhere to specific protocols for dispensing controlled substances, including verification of prescriptions and patient identification.

Patent Term Restoration and Data Exclusivity

• Patent Term Extension (PTE): If the drug product based on Patent 9,138,456 experienced lengthy FDA review periods, the patent holder may be eligible for PTE to recover some of the lost patent term.
• Data Exclusivity: Even after patent expiration, the FDA may grant periods of data exclusivity for new drugs. For example, a 5-year data exclusivity period is typically granted for NCEs, preventing ANDA approval for that period unless it's a 180-day exclusivity triggered by an ANDA filer. For a new formulation of an already approved drug, the exclusivity period might be shorter (e.g., 3 years for certain new clinical investigations).

The regulatory landscape for sublingual buprenorphine for pain is shaped by its status as a controlled substance and the rigorous FDA approval process for pharmaceuticals. Navigating these regulations is as critical as understanding the patent's claims for successful commercialization.

What is the Intellectual Property (IP) Strategy Implied by this Patent?

The IP strategy behind Patent 9,138,456 focuses on protecting a specific dosage form and method of administration for a known active pharmaceutical ingredient (API), buprenorphine, for the indication of pain. This approach aims to create a commercially viable product with a distinct market position.

Protecting the Dosage Form

The patent's core claims are directed towards a sublingual film. This signifies a strategy to differentiate from existing buprenorphine products (e.g., sublingual tablets, injections, patches) by offering a novel delivery system. The innovation lies not in the API itself, but in:

• The physical form: A thin, flexible film.
• The delivery route: Sublingual (dissolves under the tongue), implying rapid onset of action and potentially reduced first-pass metabolism compared to oral ingestion.
• Specific excipients: Mucoadhesive polymers and taste-masking agents are explicitly claimed, suggesting these are critical for the film's performance and patient compliance.
• Performance characteristics: Rapid dissolution time (30 seconds to 5 minutes) is a key feature.

This strategy aims to secure a market for patients who require fast pain relief and may experience side effects or compliance issues with other forms of buprenorphine.

Broadening Protection Through Method Claims

Claims 7-11 extend protection to the method of treating pain. This is crucial for several reasons:

• Reinforcing the Indication: It clearly defines the intended therapeutic use, preventing others from using the patented film for pain management, even if they could theoretically obtain the film through other means (though this is unlikely given controlled substance regulations).
• Blocking Competitor Uses: If another entity were to develop a similar sublingual film, these method claims would prevent them from marketing it specifically for pain relief.
• Defending Against Generic Challenges: Method of use patents can be a layer of defense against generic manufacturers who might try to produce the drug substance but are blocked from using it for the patented indication.

Targeting Specific Dosage Ranges

Claims 5, 8, and 9 specify buprenorphine hydrochloride amounts ranging from approximately 2 mg to 8 mg, and also refer back to the broader 2 mg to 16 mg range in Claim 1. This indicates a strategic focus on:

• Optimizing for Pain Management: Lower doses of opioids are generally preferred for chronic pain compared to acute, severe pain or opioid use disorder treatment. The 2-16 mg range is typical for analgesic doses.
• Product Differentiation: Different dosage strengths allow for titration and personalized treatment, catering to a wider spectrum of pain severity. Protecting specific dose ranges within the film formulation ensures that variations are also covered.

Exclusivity and Market Dominance

The overall IP strategy appears designed to achieve market exclusivity for a differentiated buprenorphine product for pain. By patenting the specific formulation (sublingual film with defined excipients and dissolution) and its method of use for pain, the patent holder aims to:

• Prevent direct competition: From generics offering the exact same sublingual film product.
• Deter development of similar products: By creating a high bar for patent infringement.
• Establish a strong market position: Based on unique delivery attributes (rapid onset, potentially better palatability, ease of use).

This patent represents a classic example of pharmaceutical IP strategy where innovation in drug delivery and formulation is used to extend market exclusivity beyond the basic patent life of the active pharmaceutical ingredient itself.

Key Takeaways

• Patent 9,138,456 protects a sublingual film formulation of buprenorphine hydrochloride for pain treatment.
• Key claims cover the composition, including specific mucoadhesive polymers, taste-masking agents, and dissolution characteristics.
• Method claims protect the use of this formulation for pain management in humans.
• The patent targets lower-to-moderate analgesic doses of buprenorphine (2 mg to 16 mg).
• Regulatory considerations include FDA approval for the drug product and DEA regulations due to buprenorphine's controlled substance status (Schedule III).
• The implied IP strategy focuses on creating market exclusivity through a novel dosage form and method of use, differentiating from existing buprenorphine products and targeting the pain management market.

Frequently Asked Questions

1. Does Patent 9,138,456 cover all forms of buprenorphine for pain? No, the patent specifically covers a sublingual film formulation. It does not cover injections, transdermal patches, or sublingual tablets unless they meet the specific claims of the patent.
2. What is the primary therapeutic indication protected by this patent? The patent explicitly protects the method of treating pain. While buprenorphine is used for opioid use disorder, this patent's claims are focused on its analgesic properties.
3. What are the key components of the claimed sublingual film? The film contains buprenorphine hydrochloride (2-16 mg), at least one mucoadhesive polymer, and at least one taste-masking agent.
4. How long is the patent term for 9,138,456 likely to be in effect? The patent was granted on August 18, 2015. Its standard term is 20 years from the filing date. However, patent term extensions due to regulatory review periods and patent adjustments could extend its enforceable life.
5. Can generic versions of this sublingual film be developed and marketed? Generic development is possible after the relevant patents expire or are invalidated. However, generic manufacturers must ensure they have freedom to operate by not infringing any active patents and will need to undergo FDA approval via an ANDA, demonstrating bioequivalence and manufacturing compliance.

Citations

[1] United States Patent 9,138,456. (2015, August 18). Composition and Method for Treating Pain. Insys Development Company, Inc.

Drugs Protected by US Patent 9,138,456

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cubist Pharms Llc	CUBICIN RF	daptomycin	POWDER;INTRAVENOUS	021572-003	Jul 6, 2016		DISCN	Yes	No			Y

International Family Members for US Patent 9,138,456

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	079127
Argentina	123846
Australia	2010321531
Brazil	112012012406
Canada	2781666