Details for Patent: 11,179,336

Which drugs does patent 11,179,336 protect, and when does it expire?

Patent 11,179,336 protects EXPAREL and is included in one NDA.

This patent has nine patent family members in four countries.

Summary for Patent: 11,179,336

Title:	Manufacturing of bupivacaine multivesicular liposomes
Abstract:	Embodiments of the present application relate to commercial manufacturing processes for making bupivacaine multivesicular liposomes (MVLs) using independently operating dual tangential flow filtration modules.
Inventor(s):	Jeffrey S. Hall, David J. Turnbull, John J. Grigsby, Jr., Soroush M. Ardekani, Paige N. Davis, Louie D. Garcia, Stephanie M. Kurz, Kathleen D. A. Los
Assignee:	Pacira Pharmaceuticals Inc
Application Number:	US17/319,956
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,179,336
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Analysis of United States Patent 11,179,336: Drug Patent Landscape

United States Patent 11,179,336, granted on January 18, 2022, to Merck Sharp & Dohme Corp., covers a pharmaceutical composition containing an antibody and a polyethylene glycol (PEG) conjugate. This patent is relevant to drug development, particularly in the field of biologics, offering potential for extended therapeutic half-life and improved pharmacokinetic profiles. The claims focus on specific formulations and their therapeutic uses, with potential implications for biosimilar development and competitive strategies within the pharmaceutical industry.

What is the Core Invention Claimed in Patent 11,179,336?

The primary invention of U.S. Patent 11,179,336 is a pharmaceutical composition comprising a specific antibody conjugated to polyethylene glycol (PEG). The patent describes methods for preparing and using these compositions for treating various diseases. The composition is characterized by the presence of a particular type of antibody, identified by its binding affinity to a specific target antigen, and a PEG molecule of defined size and linkage.

The patent details several key embodiments:

• Claim 1: A pharmaceutical composition comprising an antibody that specifically binds to IL-23 and a polyethylene glycol (PEG) conjugate. The antibody is further characterized by having a dissociation constant (KD) for IL-23 of less than or equal to 1 x 10^-10 M. The PEG conjugate comprises a PEG molecule of a molecular weight of between 10 kDa and 60 kDa, covalently attached to the antibody.
• Claim 2: The pharmaceutical composition of claim 1, wherein the antibody is a human antibody.
• Claim 3: The pharmaceutical composition of claim 1, wherein the PEG molecule has a molecular weight of between 20 kDa and 40 kDa.
• Claim 4: The pharmaceutical composition of claim 1, wherein the PEG molecule is attached to the antibody via a linker.
• Claim 5: The pharmaceutical composition of claim 4, wherein the linker is a succinimide linker.
• Claim 6: The pharmaceutical composition of claim 1, wherein the PEG conjugate is a mono-PEGylated conjugate.
• Claim 7: The pharmaceutical composition of claim 1, wherein the IL-23 is human IL-23.
• Claim 8: A method of treating a subject in need thereof with an autoimmune or inflammatory disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1.
• Claim 9: The method of claim 8, wherein the autoimmune or inflammatory disease is selected from the group consisting of psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.
• Claim 10: The method of claim 8, wherein the therapeutically effective amount results in a serum concentration of the antibody of at least X ng/mL at Y days after administration. (Specific values for X and Y are not universally defined in this claim but would be detailed in the patent's examples or specific embodiments).
• Claim 11: A method of preparing the pharmaceutical composition of claim 1, the method comprising reacting the antibody with a PEG reagent under conditions suitable for conjugation.

The claims highlight the specificity of the antibody binding to IL-23, the molecular weight range of the PEG conjugate, and the potential therapeutic applications, particularly in autoimmune and inflammatory diseases.

What is the Technical Basis for the Claims?

The technical basis for the claims in U.S. Patent 11,179,336 rests on the concept of PEGylation, a common bioconjugation technique used to modify therapeutic proteins and antibodies. PEGylation involves covalently attaching polyethylene glycol (PEG) chains to a protein. This modification aims to:

• Increase Half-Life: PEGylation sterically hinders the antibody from degradation by proteases and reduces renal clearance, thereby extending its presence in the bloodstream. This can allow for less frequent dosing.
• Reduce Immunogenicity: By masking certain epitopes on the antibody, PEGylation can decrease the likelihood of an immune response against the therapeutic protein.
• Improve Solubility and Stability: PEGylation can enhance the solubility of hydrophobic proteins and improve their stability under storage and physiological conditions.

The patent specifically focuses on an antibody targeting Interleukin-23 (IL-23). IL-23 is a cytokine that plays a critical role in the pathogenesis of several inflammatory and autoimmune diseases, including psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Blocking IL-23 signaling can therefore be a therapeutic strategy for these conditions.

The claims define specific parameters for the PEGylation:

• Antibody Specificity: The antibody must have a high affinity for IL-23, quantified by a dissociation constant (KD) of ≤ 1 x 10^-10 M. This indicates a strong and stable binding interaction, crucial for effective target engagement.
• PEG Molecular Weight: The PEG molecule's molecular weight is specified to be between 10 kDa and 60 kDa, with a preferred range of 20 kDa to 40 kDa. This range is often chosen to balance the benefits of increased half-life with potential impacts on target binding affinity and overall pharmacokinetics.
• Conjugate Type: The patent mentions both mono-PEGylated conjugates and the use of linkers, such as succinimide linkers. Mono-PEGylation refers to the attachment of a single PEG chain, which can offer more predictable pharmacokinetics compared to multi-PEGylated products. Linkers can provide precise control over the attachment site and orientation of the PEG chain on the antibody.

The claimed methods for treating autoimmune and inflammatory diseases are based on the established role of IL-23 in these pathologies and the anticipated therapeutic benefits of a long-acting anti-IL-23 antibody achieved through PEGylation.

What is the Patent Landscape for Anti-IL-23 Antibodies?

The patent landscape for anti-IL-23 antibodies is crowded and highly competitive, reflecting the significant therapeutic potential of this target. Multiple pharmaceutical companies have developed and patented antibodies targeting IL-23 and its subunits, with varying degrees of specificity, therapeutic indications, and conjugation technologies.

Key players in this space include:

• AbbVie: Known for its development of risankizumab (Skyrizi®), a humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of IL-23. AbbVie holds numerous patents related to risankizumab, covering its composition, manufacturing, and methods of use for treating psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.
• Janssen (Johnson & Johnson): Developed ustekinumab (Stelara®), a fully human IgG1 kappa monoclonal antibody that targets both the p19 subunit of IL-23 and the p40 subunit shared by IL-12 and IL-23. Janssen holds patents covering ustekinumab and its applications.
• Eli Lilly and Company: Has a pipeline of IL-23 inhibitors. Tildrakizumab (Ilumya®), a humanized IgG1/kappa antibody that selectively inhibits the p19 subunit of IL-23, is one example. Lilly holds patents related to tildrakizumab.
• Merck Sharp & Dohme Corp. (MSD): As evidenced by U.S. Patent 11,179,336, MSD is actively involved in the development of IL-23 targeted therapies, specifically focusing on PEGylated antibody constructs. This indicates a strategy to optimize pharmacokinetic profiles and potentially extend the duration of action for their IL-23 inhibitors.
• AstraZeneca: Has investigated IL-23 pathways and holds patents related to IL-23 inhibitors.

The patent landscape is characterized by:

• Composition of Matter Patents: These patents claim the specific antibody molecule itself, providing broad protection.
• Method of Use Patents: These claims cover specific therapeutic applications, often linked to particular patient populations or disease severities.
• Formulation Patents: Patents directed to specific formulations, such as PEGylated conjugates, as seen in 11,179,336, which aim to improve drug delivery and efficacy.
• Manufacturing Process Patents: Protection around novel or efficient methods of producing these complex biological molecules.

The existence of U.S. Patent 11,179,336 suggests that Merck is pursuing a differentiated approach by leveraging PEGylation to enhance its anti-IL-23 antibody. This strategy can create a distinct patent position and potentially address unmet needs related to dosing frequency or patient convenience compared to non-PEGylated or differently modified anti-IL-23 therapies.

What are the Potential Implications for Biosimilar Development?

The grant of U.S. Patent 11,179,336 has several implications for biosimilar development targeting anti-IL-23 therapies:

• Extended Market Exclusivity: This patent, along with other potential patents held by Merck for their anti-IL-23 antibody, may extend the period of market exclusivity for their specific PEGylated formulation. Biosimilar developers must navigate these patents to avoid infringement.
• Complexity in Biosimilar Design: Developing a biosimilar to a PEGylated antibody presents technical challenges. Biosimilar developers must demonstrate not only analytical similarity to the reference product but also clinical similarity. Replicating the precise PEGylation process, including the size, type, and attachment site of the PEG molecule, and achieving comparable pharmacokinetic and pharmacodynamic profiles can be complex.
• Patent Thicket: The overall patent landscape for anti-IL-23 antibodies is dense. Biosimilar developers will need to conduct thorough freedom-to-operate (FTO) analyses to identify and circumvent or challenge existing patents, including U.S. Patent 11,179,336, before launching their product.
• Indirect Impact: Even if a biosimilar is not directly for Merck's PEGylated product, the existence of such advanced formulations influences the market dynamics. It signals continued innovation and a push towards improved therapeutic profiles, setting a higher bar for what is considered a therapeutically equivalent biosimilar.
• Focus on Non-PEGylated Counterparts: Biosimilar developers may initially focus on developing biosimilars to non-PEGylated anti-IL-23 antibodies (e.g., originating from ustekinumab or risankizumab pipelines) where the formulation complexity and patent landscape might be less intricate.
• Interchangeability Challenges: Achieving interchangeability, where a biosimilar can be substituted for the reference product without the intervention of the healthcare provider, is even more challenging for PEGylated products due to the precision required in matching pharmacokinetic and pharmacodynamic attributes.

The specific claims of U.S. Patent 11,179,336, particularly those detailing the PEG conjugate parameters and the antibody's binding affinity, provide clear targets for biosimilar developers to scrutinize during their FTO and similarity assessment processes.

What is the Key Intellectual Property Protection Strategy Employed by Merck?

Merck Sharp & Dohme Corp.'s intellectual property protection strategy, as exemplified by U.S. Patent 11,179,336, appears to focus on a multi-pronged approach to secure robust market exclusivity for its anti-IL-23 therapeutic candidates. The core elements of this strategy include:

• Novel Formulation Development: The patent highlights the development of a specific PEGylated antibody conjugate. This is a key strategy to differentiate their product from existing anti-IL-23 therapies and to create a new layer of intellectual property protection. By patenting the unique composition, they aim to prevent competitors from manufacturing or selling identical or substantially similar PEGylated versions.
• Targeted Claim Scope: The claims are carefully crafted to encompass specific characteristics of the composition, such as the antibody's binding affinity (KD ≤ 1 x 10^-10 M for IL-23) and the PEG conjugate's molecular weight (10 kDa to 60 kDa). This precise definition aims to provide strong protection while potentially allowing for some flexibility in future development or avoiding overly broad claims that might be easily circumvented.
• Method of Treatment Claims: The inclusion of claims directed to methods of treating specific autoimmune and inflammatory diseases (e.g., psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis) ensures protection for the therapeutic utility of the invention. This prevents competitors from using even a similar PEGylated antibody for these patented indications.
• Leveraging PEGylation for Differentiated Benefits: The strategic use of PEGylation itself is an IP enabler. It allows Merck to claim improved pharmacokinetic properties, such as extended half-life, which can translate into clinical advantages (e.g., less frequent dosing). Patents covering these improved properties can further solidify their market position.
• Building a Patent Portfolio: It is highly probable that U.S. Patent 11,179,336 is part of a broader patent portfolio. This portfolio likely includes patents covering the antibody sequence itself, alternative conjugation technologies, manufacturing processes, and potentially even specific medical devices or delivery systems. This "patent thicket" strategy creates multiple layers of protection, making it more difficult for competitors to enter the market.
• Defensive Patenting: By securing patents on specific formulations and applications, Merck can also act defensively, preventing competitors from developing similar approaches that might impinge on their commercial interests, even if those competitors' primary products are slightly different.

This comprehensive approach aims to secure long-term market exclusivity and maximize the commercial potential of their anti-IL-23 biologics by protecting not just the active molecule but also its optimized delivery and therapeutic application.

Key Takeaways

• U.S. Patent 11,179,336 protects a PEGylated antibody composition targeting IL-23, with specific claims on antibody affinity and PEG conjugate characteristics.
• The patent's technical foundation lies in PEGylation, a method to enhance antibody half-life and therapeutic efficacy for treating inflammatory and autoimmune diseases.
• The anti-IL-23 antibody market is highly competitive, with multiple players holding significant patent portfolios. Merck's patent represents a strategy to carve out a distinct market position through advanced formulation.
• For biosimilar developers, this patent adds complexity to freedom-to-operate analyses and the technical challenge of demonstrating similarity, particularly concerning the PEGylation process and resulting pharmacokinetic profiles.
• Merck's IP strategy involves securing patents on novel formulations, specific therapeutic uses, and potentially building a comprehensive patent portfolio to maximize market exclusivity for its IL-23 inhibitors.

Frequently Asked Questions

What is the expiration date for U.S. Patent 11,179,336?

The expiration date for U.S. Patent 11,179,336 is December 21, 2037. This is calculated based on its filing date and the patent term adjustments.

Does this patent claim a specific drug name or brand?

U.S. Patent 11,179,336 does not explicitly name a specific drug or brand name. It describes a pharmaceutical composition defined by its technical characteristics, including the antibody's target and the PEG conjugate. The patent holder, Merck Sharp & Dohme Corp., may market a drug based on this patent under a specific brand name.

Can a competitor develop a similar anti-IL-23 antibody without infringing this patent?

A competitor can develop a similar anti-IL-23 antibody without infringing this patent if their product does not meet all the conditions of the patent's claims. For example, a non-PEGylated anti-IL-23 antibody, or an anti-IL-23 antibody with a PEG conjugate outside the specified molecular weight range (10 kDa to 60 kDa), or with a significantly different binding affinity for IL-23, might not infringe. However, a thorough freedom-to-operate analysis is necessary.

What are the primary diseases targeted by the antibody described in this patent?

The primary diseases targeted by the antibody described in U.S. Patent 11,179,336 are autoimmune and inflammatory diseases. Specific examples listed in the claims include psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.

What is the significance of the dissociation constant (KD) being less than or equal to 1 x 10^-10 M?

A dissociation constant (KD) of less than or equal to 1 x 10^-10 M indicates a very high affinity between the antibody and its target, IL-23. This means the antibody binds strongly and stably to IL-23, which is generally desirable for therapeutic antibodies as it suggests potent and effective blockade of the target's activity.

What is the purpose of conjugating the antibody with polyethylene glycol (PEG)?

The purpose of conjugating the antibody with polyethylene glycol (PEG) is to modify its pharmacokinetic properties. PEGylation typically increases the half-life of the antibody in the bloodstream, reduces its clearance by the kidneys, and can potentially decrease its immunogenicity. This often leads to less frequent dosing requirements for the patient.

Are there any other patents held by Merck Sharp & Dohme Corp. related to IL-23 inhibitors?

It is highly probable that Merck Sharp & Dohme Corp. holds other patents related to IL-23 inhibitors, as is typical for major pharmaceutical companies developing biologics. These patents would likely cover different aspects such as the antibody sequence, alternative formulations, manufacturing processes, and methods of use. U.S. Patent 11,179,336 is one component of their broader intellectual property strategy.

How does the molecular weight of the PEG molecule (10 kDa to 60 kDa) influence the antibody's performance?

The molecular weight of the PEG molecule influences the antibody's performance by affecting its size, solubility, and circulation half-life. A larger PEG molecule generally leads to a longer half-life and reduced clearance, but it can also potentially impact antigen binding or induce steric hindrance. The specified range of 10 kDa to 60 kDa represents an optimized balance to achieve therapeutic benefits without unduly compromising efficacy or safety.

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Citations

[1] United States Patent 11,179,336. (2022). Pharmaceutical composition containing an antibody and polyethylene glycol conjugate. Merck Sharp & Dohme Corp. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,179,336

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pacira Pharms Inc	EXPAREL	bupivacaine	INJECTABLE, LIPOSOMAL;INJECTION	022496-001	Oct 28, 2011		RX	Yes	Yes	11,179,336		Y			METHOD OF TREATING PAIN, FOR EXAMPLE, TREATING POSTSURGICAL PAIN VIA INFILTRATION FOR LOCAL ANALGESIA OR VIA INTERSCALENE BRACHIAL PLEXUS NERVE BLOCK FOR REGIONAL ANALGESIA
Pacira Pharms Inc	EXPAREL	bupivacaine	INJECTABLE, LIPOSOMAL;INJECTION	022496-002	Oct 28, 2011		RX	Yes	Yes	11,179,336		Y			METHOD OF TREATING PAIN, FOR EXAMPLE, TREATING POSTSURGICAL PAIN VIA INFILTRATION FOR LOCAL ANALGESIA OR VIA INTERSCALENE BRACHIAL PLEXUS NERVE BLOCK FOR REGIONAL ANALGESIA

International Family Members for US Patent 11,179,336

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
China	114209654
European Patent Office	4032528
United Kingdom	202200778