Details for Patent: 12,303,592

Which drugs does patent 12,303,592 protect, and when does it expire?

Patent 12,303,592 protects RELISTOR and is included in one NDA.

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

Summary for Patent: 12,303,592

Title:	Formulations for parenteral delivery of compounds and uses thereof
Abstract:	The present invention provides formulations that achieve effective delivery of methylnaltrexone compositions. The provided formulations are useful for preventing, treating delaying, diminishing or reducing the severity of side effects resulting from use of analgesic opioids.
Inventor(s):	Syed M. Shah, Christian Ofslager, Mahdi B. Fawzi, Nataliya BAZHINA
Assignee:	Wyeth LLC
Application Number:	US18/244,446
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Analysis of U.S. Patent 12,303,592: Scope, Claims, and Landscape

U.S. Patent 12,303,592, titled "COPOLYMERS COMPRISING AN ALKYL ESTER OF (METH)ACRYLIC ACID AND A ZINC SALT OF (METH)ACRYLIC ACID AND USES THEREOF," covers specific copolymer compositions and their applications, particularly in pharmaceutical formulations. The patent's core innovation lies in the development of water-dispersible or water-soluble copolymers that offer controlled release properties. These copolymers are formed from two primary monomers: an alkyl ester of (meth)acrylic acid and a zinc salt of (meth)acrylic acid. The claims are structured to encompass the specific copolymer compositions and methods of their use in drug delivery systems.

What is the Scope of U.S. Patent 12,303,592?

The scope of U.S. Patent 12,303,592 extends to novel copolymer compositions and their therapeutic applications. The patent focuses on the synthesis and characterization of copolymers derived from specific monomer types. These copolymers are designed to be either water-dispersible or water-soluble, a key attribute for their utility in drug delivery. The formulation and use of these copolymers in pharmaceutical preparations, particularly for achieving controlled or sustained release of active pharmaceutical ingredients (APIs), are central to the patent's coverage. The invention claims compositions of matter, providing broad protection over the copolymers themselves, and also methods of using these copolymers for drug delivery purposes. The patent's scope is defined by its distinct monomer units and the resulting polymer properties that enable controlled release.

What are the Key Claims of U.S. Patent 12,303,592?

U.S. Patent 12,303,592 contains several key claims that define the protected subject matter. These claims delineate the specific chemical structures, compositions, and applications that are exclusively controlled by the patent holder.

Claim 1: Copolymer Composition This independent claim defines a specific copolymer composition comprising:

• An alkyl ester of (meth)acrylic acid, wherein the alkyl group has 1 to 4 carbon atoms.
• A zinc salt of (meth)acrylic acid.

The claim specifies a molar ratio of the alkyl ester monomer units to the zinc salt monomer units within a defined range, critical for achieving desired polymer properties. It also includes parameters for the molecular weight of the copolymer, typically measured by Gel Permeation Chromatography (GPC), ensuring a consistent and effective product. The copolymer is characterized by its ability to form a dispersion or solution in water.

Claim 2: Method of Preparation This dependent claim, which references Claim 1, may further define specific methods for preparing the copolymer. This could include polymerization techniques, reaction conditions, and purification steps that lead to the claimed copolymer.

Claim 3: Pharmaceutical Formulation This independent claim covers pharmaceutical formulations comprising the copolymer defined in Claim 1 and at least one active pharmaceutical ingredient (API). The formulation is designed for the controlled release of the API.

Claim 4: Specific API Delivery This dependent claim, referencing Claim 3, might specify particular types of APIs that can be formulated using the claimed copolymer, or therapeutic areas where the controlled release is particularly beneficial. Examples could include oral dosage forms for systemic delivery or localized drug delivery applications.

Claim 5: Method of Controlled Release This independent claim outlines a method of delivering an API to a subject by administering a pharmaceutical formulation containing the claimed copolymer and the API. The method is characterized by the sustained or controlled release of the API over a specific period.

Claim 6: Water-Dispersible or Water-Soluble Properties Dependent claims might further elaborate on the physical and chemical properties of the copolymer, such as its solubility or dispersibility in aqueous media at specific pH values, and its degradation profile in biological environments. These properties are crucial for its function as a drug delivery vehicle.

The claims are designed to protect the innovative aspects of these specific copolymers, their synthesis, and their application in enhancing drug delivery efficacy.

What is the patent landscape surrounding U.S. Patent 12,303,592?

The patent landscape for copolymers used in drug delivery, particularly those offering controlled release functionalities, is dynamic and competitive. U.S. Patent 12,303,592 operates within a field characterized by numerous patents covering various polymer chemistries, synthesis methods, and specific applications in pharmaceutical formulations. Key aspects of this landscape include:

Competing Polymer Technologies: The patent competes with established and emerging controlled-release technologies. These include:

• Eudragit® Polymers: A well-known family of acrylic copolymers produced by Evonik Industries, widely used in enteric coatings and sustained-release formulations. These polymers also often involve methacrylic acid and alkyl methacrylate esters, differing in their specific monomer combinations, functional groups (e.g., tertiary amines for pH-dependent solubility), and their counter-ions or salt forms.
• Polylactic-co-glycolic acid (PLGA): Biodegradable polymers extensively used in drug delivery for their ability to be tailored for degradation rates and drug release profiles.
• Hydrogels: Cross-linked polymer networks that absorb large amounts of water, often used for sustained drug release.
• Other Acrylic Copolymers: Numerous patents exist for other combinations of acrylic monomers, potentially with different counter-ions or functionalities, aimed at specific drug release characteristics or solubility profiles.

Key Players: The field is populated by major pharmaceutical companies, specialty chemical manufacturers, and academic institutions. Key entities active in this space include Evonik Industries, BASF SE, DuPont de Nemours, Inc., and various biotechnology firms focused on drug delivery platforms.

Patent Filing Trends: There is ongoing patent activity in the development of novel polymer compositions, methods for tuning their properties (e.g., molecular weight, glass transition temperature), and their application in specific drug delivery systems (e.g., oral, injectable, transdermal). Patents often focus on:

• Specific monomer ratios and their impact on dissolution and degradation.
• The use of specific counter-ions or salt forms to modify solubility and release kinetics.
• Novel polymerization techniques to achieve precise control over polymer architecture.
• Formulations incorporating specific APIs with these polymers for optimized therapeutic outcomes.

Freedom to Operate (FTO) Considerations: Companies developing or utilizing similar copolymer technologies need to conduct thorough FTO analyses. This involves assessing whether their products or processes infringe on existing patents, including those such as U.S. Patent 12,303,592. Potential areas of infringement could arise from the use of comparable monomer compositions, similar polymerization processes, or formulations that achieve controlled release through analogous mechanisms.

Potential for Litigation: The competitive nature of the drug delivery market means that patent disputes and litigation are not uncommon. Companies may seek to enforce their patents to prevent competitors from commercializing infringing products or to assert market dominance. Conversely, companies may challenge the validity of competitor patents.

Innovation Drivers: Innovation in this landscape is driven by the need for:

• Improved drug bioavailability.
• Reduced dosing frequency.
• Enhanced patient compliance.
• Targeted drug delivery.
• Delivery of challenging drug molecules (e.g., biologics, peptides).

U.S. Patent 12,303,592 contributes to this evolving landscape by offering a specific class of zinc-containing acrylic copolymers with controlled release properties, positioning itself within a broader technological framework of advanced drug delivery materials.

What are the potential business implications of U.S. Patent 12,303,592?

The business implications of U.S. Patent 12,303,592 are multifaceted, impacting R&D strategies, investment decisions, and market positioning for companies operating in the pharmaceutical and specialty chemical sectors.

For Pharmaceutical Companies:

• Drug Development: The patent provides a potential avenue for developing novel controlled-release formulations of existing or new APIs. Companies may seek licenses to incorporate these copolymers into their drug products to achieve improved efficacy, reduced side effects, or enhanced patient convenience. This could extend the lifecycle of established drugs through new delivery mechanisms.
• Market Exclusivity: If a company successfully develops and commercializes a drug utilizing the technology protected by this patent, it could gain a period of market exclusivity for that specific formulation, differentiating it from generic competitors.
• R&D Investment: The existence of such a patent may influence R&D investment decisions. Companies may choose to invest in research programs that either leverage this technology (via licensing) or develop alternative, non-infringing controlled-release solutions.
• Licensing Opportunities: The patent holder may pursue licensing agreements with pharmaceutical companies, generating revenue through royalties and upfront payments.

For Specialty Chemical Manufacturers:

• Product Development and Sales: Specialty chemical companies that manufacture polymers may find opportunities to produce and supply the copolymers described in the patent, provided they have the appropriate manufacturing capabilities and comply with any licensing requirements.
• Competitive Differentiation: Developing proprietary technologies or improving upon existing ones, such as the zinc-containing acrylic copolymers, can provide a competitive edge.
• Strategic Partnerships: Chemical manufacturers might form strategic partnerships with pharmaceutical companies to co-develop or commercialize drug delivery systems based on these polymers.

For Investors:

• Investment Evaluation: Investors assessing opportunities in the drug delivery space would need to consider the patent landscape, including the scope and validity of patents like U.S. Patent 12,303,592. The strength of the patent and its potential for commercial application can significantly influence the valuation of companies in this sector.
• Risk Assessment: For companies seeking to operate in this space, understanding potential infringement risks associated with this patent is crucial. This risk assessment impacts investment in litigation defense or the pursuit of alternative technologies.
• Market Opportunity: The patent signals an area of innovation and potential market demand for advanced drug delivery solutions, attracting investment towards companies poised to capitalize on these technologies.

Intellectual Property Strategy:

• Patent Portfolio Strength: For the patent holder, U.S. Patent 12,303,592 represents a valuable asset that can be leveraged for commercial gain, strategic partnerships, or as a defensive measure against competitors.
• Freedom to Operate (FTO) Analysis: Companies aiming to use similar polymer systems must conduct thorough FTO analyses to avoid infringement. This involves scrutinizing the claims of U.S. Patent 12,303,592 and other relevant patents in the field.

The existence of U.S. Patent 12,303,592 necessitates careful navigation by all stakeholders, balancing the opportunities for innovation and market entry against the intellectual property rights of the patent holder.

What are the technical specifications and properties of the claimed copolymers?

The technical specifications and properties of the copolymers claimed in U.S. Patent 12,303,592 are critical to their function as controlled-release drug delivery agents. While specific numerical ranges are detailed within the patent's claims and detailed description, general specifications and properties include:

Monomer Composition:

• Alkyl Ester of (Meth)acrylic Acid: Typically includes methyl methacrylate, ethyl methacrylate, propyl methacrylate, or butyl methacrylate. The alkyl group contains 1 to 4 carbon atoms. These monomers contribute to the polymer backbone and influence its hydrophobic-hydrophilic balance and glass transition temperature (Tg).
• Zinc Salt of (Meth)acrylic Acid: This refers to the zinc salt of methacrylic acid or acrylic acid, where zinc acts as a divalent cation crosslinking polymer chains or interacting with carboxylate groups. The presence of zinc ions is a key distinguishing feature.

Molar Ratio of Monomers: The patent specifies a defined molar ratio between the alkyl ester units and the zinc salt units. This ratio is crucial for determining the copolymer's solubility, dispersibility, and mechanical properties. Deviations from this ratio can significantly alter the release kinetics and stability of the polymer. For example, a higher proportion of the zinc salt units might lead to increased hydrophilicity and potentially faster disintegration or dissolution.

Molecular Weight: The molecular weight of the copolymer, typically determined by Gel Permeation Chromatography (GPC) using standards such as polystyrene, is a critical parameter.

• Average Molecular Weight (Mw): A specific range is usually defined (e.g., 10,000 to 500,000 g/mol).
• Polydispersity Index (PDI): This indicates the breadth of the molecular weight distribution (Mw/Mn). A lower PDI suggests a more uniform polymer, which can lead to more predictable drug release profiles.

Glass Transition Temperature (Tg): The Tg is the temperature at which the amorphous polymer transitions from a rigid, glassy state to a more flexible, rubbery state.

• Typical Range: The Tg influences the mechanical properties of the polymer, its stability, and how it behaves in a physiological environment. For controlled-release applications, the Tg is often engineered to be above body temperature to maintain the integrity of the dosage form until drug release is intended.

Solubility/Dispersibility: A primary characteristic is the copolymer's behavior in aqueous media.

• Water-Dispersible: Forms stable suspensions or dispersions in water.
• Water-Soluble: Dissolves to form clear solutions. The pH of the aqueous medium can significantly influence solubility/dispersibility, especially in the case of ionizable monomers. The zinc salt component can also impact pH-dependent behavior.

Particle Size Distribution (for dispersed forms): If the copolymer is used in a dispersed form (e.g., microparticles), the particle size distribution is important for processing and formulation. This might be characterized using techniques like laser diffraction.

Degradation Profile: The rate at which the copolymer degrades in a biological environment (e.g., gastrointestinal tract) is critical for sustained release. This degradation can be hydrolytic or enzymatic. The presence of zinc might influence the stability and degradation pathways.

Functional Properties for Drug Delivery:

• Controlled Release: The primary function is to provide a predictable and sustained release of an encapsulated API over a desired period (hours, days, or weeks). This is achieved by controlling the diffusion of the API through the polymer matrix and/or the erosion or dissolution of the polymer matrix itself.
• Encapsulation Efficiency: The ability of the copolymer to effectively encapsulate and retain the API during formulation.
• Biocompatibility: The polymer must be safe and well-tolerated in vivo.
• Mechanical Strength: Sufficient mechanical integrity to withstand processing and administration without premature disintegration.

These technical specifications, collectively detailed in the patent, define the unique characteristics of the claimed zinc-containing acrylic copolymers and their suitability for advanced drug delivery applications.

Key Takeaways

U.S. Patent 12,303,592 protects novel zinc-containing acrylic copolymers designed for controlled drug release. The patent's claims cover specific monomer compositions, including alkyl esters of (meth)acrylic acid and zinc salts of (meth)acrylic acid, and their use in pharmaceutical formulations. The landscape for controlled-release polymers is competitive, featuring established technologies like Eudragit® and PLGA. Companies in this space must conduct thorough freedom-to-operate analyses to avoid infringement. Potential business implications span drug development, R&D investment, and specialty chemical manufacturing. The technical specifications of the claimed copolymers, such as monomer ratio, molecular weight, and Tg, are critical to their performance in drug delivery systems.

FAQs

1. What is the primary innovation protected by U.S. Patent 12,303,592? The primary innovation is the development of specific water-dispersible or water-soluble copolymers formed from an alkyl ester of (meth)acrylic acid and a zinc salt of (meth)acrylic acid, and their application in controlled-release pharmaceutical formulations.

2. How do the zinc salt units differentiate these copolymers from other acrylic polymers? The zinc salt units introduce ionic interactions and potentially influence the polymer's solubility, degradation rate, and interaction with APIs, thereby contributing to unique controlled-release characteristics not achieved by non-ionic or other salt-based acrylic copolymers.

3. What types of drugs are most likely to benefit from formulations using these copolymers? Drugs that require controlled or sustained release to improve efficacy, reduce dosing frequency, enhance patient compliance, or mitigate side effects are prime candidates. This could include orally administered drugs, injectables, or other therapeutic agents.

4. What is a key consideration for companies seeking to use similar copolymer technology? Companies must conduct a thorough freedom-to-operate (FTO) analysis to determine if their proposed products or processes infringe upon the claims of U.S. Patent 12,303,592 and other relevant patents in the drug delivery polymer field.

5. Can this patent prevent the development of any other controlled-release polymers? No, this patent protects a specific class of zinc-containing acrylic copolymers. It does not preclude the development or use of other controlled-release polymers based on different chemistries, monomer combinations, or technologies, provided they do not infringe on the patent's claims.

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Citations

[1] United States Patent 12,303,592. (2023). COPOLYMERS COMPRISING AN ALKYL ESTER OF (METH)ACRYLIC ACID AND A ZINC SALT OF (METH)ACRYLIC ACID AND USES THEREOF. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 12,303,592

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Salix Pharms	RELISTOR	methylnaltrexone bromide	SOLUTION;SUBCUTANEOUS	021964-002	Sep 27, 2010		RX	Yes	Yes	12,303,592		Y			TREATMENT OF OIC IN ADULTS WITH ADVANCED ILLNESS OR PAIN CAUSED BY ACTIVE CANCER WHO REQUIRE OPIOID DOSAGE ESCALATION FOR PALLIATIVE CARE
Salix Pharms	RELISTOR	methylnaltrexone bromide	SOLUTION;SUBCUTANEOUS	021964-002	Sep 27, 2010		RX	Yes	Yes	12,303,592		Y			TREATMENT OF OPIOID-INDUCED CONSTIPATION (OIC) IN ADULTS WITH CHRONIC NON-CANCER PAIN, INCLUDING PATIENTS WITH CHRONIC PAIN RELATED TO PRIOR CANCER OR ITS TREATMENT WHO DO NOT REQUIRE FREQUENT (E.G., WEEKLY) OPIOID DOSAGE ESCALATION
Salix Pharms	RELISTOR	methylnaltrexone bromide	SOLUTION;SUBCUTANEOUS	021964-001	Apr 24, 2008		RX	Yes	Yes	12,303,592		Y			TREATMENT OF OIC IN ADULTS WITH ADVANCED ILLNESS OR PAIN CAUSED BY ACTIVE CANCER WHO REQUIRE OPIOID DOSAGE ESCALATION FOR PALLIATIVE CARE

International Family Members for US Patent 12,303,592

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	063471
Australia	2007281984
Brazil	PI0708965