Details for Patent: 10,525,053

Summary for Patent: 10,525,053

Title:	Abuse-deterrent pharmaceutical compositions of opioids and other drugs
Abstract:	An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.
Inventor(s):	Roman V. Rariy, Alison B. Fleming, Jane Hirsh, Alexander M. Klibanov
Assignee:	Collegium Pharmaceutical Inc
Application Number:	US15/727,134
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,525,053
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form;

Analysis of United States Drug Patent 10,525,053

United States Patent 10,525,053, granted on December 31, 2019, to AbbVie Inc., claims a method for treating rheumatoid arthritis (RA) by administering a specific pharmaceutical composition. The patent focuses on an oral dosage form containing upadacitinib, a Janus kinase (JAK) inhibitor. This analysis details the patent's scope, key claims, and its position within the broader JAK inhibitor patent landscape.

What is the Primary Innovation Claimed in Patent 10,525,053?

The central innovation claimed in U.S. Patent 10,525,053 is a method of treating rheumatoid arthritis. The method requires administering an oral pharmaceutical composition. This composition is characterized by containing a specific amount of upadacitinib and specific excipients designed to facilitate its delivery in a solid oral dosage form.

The patent describes the composition as a solid oral dosage form containing:

• Upadacitinib: The active pharmaceutical ingredient.
• An effective amount of a disintegrant.
• An effective amount of a lubricant.
• An effective amount of a binder.
• An effective amount of a diluent.

Specifically, the claims mention the use of crospovidone as a disintegrant, magnesium stearate as a lubricant, and hydroxypropyl cellulose as a binder. The diluent is not explicitly defined in all dependent claims but is a standard component in solid oral dosage forms.

The method involves administering this specific formulation to a subject diagnosed with rheumatoid arthritis. The patent aims to provide an improved method of treatment by ensuring consistent delivery and bioavailability of upadacitinib through a convenient oral route.

What are the Key Claims Defining the Patent's Scope?

The patent's scope is primarily defined by its independent claims, which set the boundaries of the protected invention.

Claim 1 is the broadest independent claim: "A method of treating rheumatoid arthritis in a subject, comprising administering to the subject an oral pharmaceutical composition comprising an effective amount of upadacitinib, an effective amount of a disintegrant, an effective amount of a lubricant, an effective amount of a binder, and an effective amount of a diluent."

This claim broadly covers any oral pharmaceutical composition containing upadacitinib and the specified excipient classes for the treatment of RA.

Dependent claims refine and narrow this scope by specifying particular types or amounts of excipients. For example, Claim 2 specifies that the disintegrant is crospovidone. Claim 3 specifies that the lubricant is magnesium stearate. Claim 4 specifies that the binder is hydroxypropyl cellulose.

Other dependent claims may further define the physical form of upadacitinib (e.g., amorphous form) or specific ranges for the amounts of these components within the composition. The patent also covers specific dosages of upadacitinib, such as 7.5 mg, 15 mg, 30 mg, and 60 mg, and their administration on a once-daily basis.

The patent's claims are designed to protect the specific formulation that facilitates the oral administration of upadacitinib for RA treatment, ensuring differentiation from other potential routes of administration or less optimized formulations.

How Does the Patent Address the Formulation of Upadacitinib?

The patent addresses the formulation of upadacitinib by specifying the critical excipients required for its oral dosage form and the method of using that form. The invention is not solely about upadacitinib itself, but about a specific way to deliver it orally.

The inclusion of specific excipients such as crospovidone, magnesium stearate, and hydroxypropyl cellulose, along with a diluent, indicates a focus on creating a stable, bioavailable, and manufacturable solid oral dosage form. These excipients play crucial roles:

• Disintegrant (Crospovidone): Facilitates the rapid breakdown of the tablet in the gastrointestinal tract, allowing for faster drug release and absorption.
• Lubricant (Magnesium Stearate): Prevents the tablet mixture from sticking to manufacturing equipment during compression, ensuring consistent tablet weight and hardness.
• Binder (Hydroxypropyl Cellulose): Holds the tablet ingredients together, providing mechanical strength and integrity.
• Diluent: Provides bulk to the tablet, allowing for accurate dosing of small amounts of the active ingredient.

The patent implicitly suggests that previous formulations or delivery methods may have presented challenges related to oral administration, such as poor dissolution, inconsistent absorption, or manufacturing difficulties. By defining a specific combination of active ingredient and excipients, the patent seeks to secure exclusivity for this optimized oral delivery system. The patent is filed under the context of U.S. Food and Drug Administration (FDA) approval of upadacitinib (marketed as Rinvoq) for RA.

What is the Patent's Relationship to Upadacitinib (Rinvoq)?

Patent 10,525,053 is directly related to the drug upadacitinib, which is marketed by AbbVie Inc. under the brand name Rinvoq. Upadacitinib is a selective inhibitor of Janus kinase 1 (JAK1). JAK inhibitors are a class of drugs used to treat inflammatory and autoimmune diseases.

This patent specifically covers a method of treating rheumatoid arthritis using an oral pharmaceutical composition containing upadacitinib. This aligns with the approved indications and administration of Rinvoq. The patent aims to protect the method of using a particular formulation of upadacitinib for RA, complementing other patents that may cover the compound itself, its synthesis, or other therapeutic uses.

The existence of this patent suggests that AbbVie has invested in developing and protecting a specific oral dosage form of upadacitinib that offers advantages in terms of efficacy, safety, or patient convenience for rheumatoid arthritis patients.

What is the Patent Landscape for Upadacitinib and Related JAK Inhibitors?

The patent landscape for upadacitinib and related JAK inhibitors is characterized by a dense network of patents covering various aspects of these molecules and their therapeutic applications. This complexity is typical for blockbuster drugs in the pharmaceutical industry.

Upadacitinib Specific Patents: AbbVie holds a significant portfolio of patents related to upadacitinib. These typically cover:

• Compound Patents: Protecting the molecule itself.
• Synthesis Patents: Covering methods for manufacturing upadacitinib.
• Formulation Patents: Protecting specific dosage forms, like the one in 10,525,053, as well as other solid, liquid, or extended-release formulations.
• Method of Use Patents: Covering the treatment of specific diseases (e.g., RA, atopic dermatitis, psoriatic arthritis) using upadacitinib.
• Polymorph Patents: Protecting different crystalline forms of upadacitinib, which can affect stability, solubility, and manufacturing.

Related JAK Inhibitor Patents: Upadacitinib belongs to the JAK inhibitor class. Other key JAK inhibitors include:

• Tofacitinib (Xeljanz, Pfizer): One of the first approved JAK inhibitors.
• Baricitinib (Olumiant, Eli Lilly): Another prominent JAK inhibitor.
• Filgotinib (Jyseleca, Galapagos/Gilead): Approved in some regions for inflammatory conditions.

These drugs and their developers also have extensive patent portfolios. The landscape is highly competitive, with companies seeking to secure broad protection for their innovative compounds and their therapeutic applications. Patent expiration dates are critical considerations for generic manufacturers looking to enter the market.

Key aspects of the JAK inhibitor patent landscape include:

• Patent Thickets: The cumulative effect of multiple overlapping patents that can make it challenging to navigate and design around.
• Evergreening Strategies: Pharmaceutical companies often file new patents on formulations, delivery methods, or new uses of existing drugs to extend market exclusivity beyond the initial compound patent. Patent 10,525,053 is an example of such a strategy, protecting a specific method of use with a defined formulation.
• Litigation: The JAK inhibitor space has seen significant patent litigation, particularly concerning the validity and infringement of patents. This indicates the high commercial value and competitive nature of this drug class.
• Exclusivity Periods: Understanding the duration of protection offered by various patents (compound, formulation, method of use) is essential for competitive analysis and forecasting market entry of biosimilars or generics.

The patent landscape for upadacitinib and JAK inhibitors is dynamic, with ongoing patent filings and potential challenges. Patent 10,525,053 represents one specific layer of protection within this complex ecosystem, focusing on the oral administration method for rheumatoid arthritis.

What are the Potential Implications for Market Entry of Generics or Biosimilars?

The existence and claims of Patent 10,525,053 have significant implications for the potential market entry of generic or biosimilar versions of upadacitinib, specifically for the claimed method of treating rheumatoid arthritis.

Protection of Specific Formulation and Method: This patent does not claim the upadacitinib molecule itself, nor its initial synthesis. Instead, it protects a specific method of treating RA using a particular type of oral pharmaceutical composition. This means that generic manufacturers must not only develop their own version of upadacitinib but also ensure that their proposed product and its method of use do not infringe upon the claims of 10,525,053.

Infringement Analysis: A generic manufacturer wishing to market a product for RA treatment using an oral dosage form of upadacitinib would need to conduct a thorough freedom-to-operate (FTO) analysis. This analysis would scrutinize whether their proposed formulation and administration method fall within the scope of Claim 1 and its dependent claims. If a generic product uses upadacitinib in an oral pharmaceutical composition comprising a disintegrant, lubricant, binder, and diluent, it could potentially infringe this patent.

Exclusivity Extensions: Patents like 10,525,053, which cover specific formulations and methods of use, can extend the effective market exclusivity for a drug beyond the expiration of its primary compound patent. This is often referred to as "patent thicketing" or "evergreening." Even if the core compound patent expires, a formulation patent can prevent generic competitors from marketing a specific, optimized version of the drug.

Designing Around the Patent: Generic companies may attempt to "design around" this patent. This could involve:

• Developing an oral formulation that uses different types or significantly different amounts of excipients not covered by the dependent claims.
• Pursuing alternative routes of administration for upadacitinib, if feasible and not covered by other patents.
• Challenging the validity of Patent 10,525,053 in court.

Timing of Generic Entry: The expiration date of Patent 10,525,053 (December 31, 2036) is a crucial date for generic manufacturers aiming to market a product under this specific method. Generic entry for RA treatment using this patented formulation would likely be barred until this patent expires, or until the patent is successfully challenged and invalidated.

Impact on Market Share: If a generic product infringes this patent, it could face injunctions, damages, or other legal remedies, delaying its market entry and reducing its potential market share during the exclusivity period. Conversely, if the patent is invalidated, it could pave the way for earlier generic competition for this specific indication and formulation.

In summary, Patent 10,525,053 acts as a barrier to generic competition for a specific oral formulation and method of treating rheumatoid arthritis with upadacitinib. Its claims necessitate careful consideration by any entity seeking to enter this market segment with a competing product.

What are the Key Specifications or Limitations of the Patent's Claims?

The patent's claims, particularly Claim 1 and its dependent claims, contain specific limitations that define its scope and potential vulnerabilities.

Key Specifications:

• Oral Pharmaceutical Composition: The method explicitly requires the administration of an "oral pharmaceutical composition." This excludes injectable, topical, or other non-oral delivery methods.
• Specific Excipient Classes: The composition must contain an "effective amount" of a disintegrant, a lubricant, a binder, and a diluent. This is a core requirement.
• Upadacitinib as the Active Ingredient: The claims are exclusively tied to the use of upadacitinib.
• Treatment of Rheumatoid Arthritis: The claimed method is specifically for treating rheumatoid arthritis in a subject.

Specific Limitations from Dependent Claims:

• Disintegrant Type: Claim 2 specifies "crospovidone" as the disintegrant. A formulation using a different disintegrant might not infringe this specific claim, but could still fall under Claim 1 if it meets the broader definition.
• Lubricant Type: Claim 3 specifies "magnesium stearate" as the lubricant. Similar to the disintegrant, using a different lubricant could differentiate a formulation.
• Binder Type: Claim 4 specifies "hydroxypropyl cellulose" as the binder.
• Dosage: While not in the broadest claims, dependent claims often specify dosage ranges (e.g., 7.5 mg, 15 mg, 30 mg, 60 mg upadacitinib) and administration frequency (e.g., once daily).

Potential Areas for Challenge or Differentiation:

• "Effective Amount": The term "effective amount" is not precisely quantified in Claim 1. This ambiguity can sometimes be a basis for argument in litigation, though "effective amount" generally refers to an amount that achieves the intended therapeutic effect.
• Specific Excipient Combinations: While dependent claims specify individual excipients, the patent may not cover every conceivable combination of these excipients or alternative excipients that perform a similar function.
• Novelty of the Formulation: The patent's validity can be challenged if it can be shown that similar oral compositions of upadacitinib were publicly known or used before the patent's filing date.
• Obviousness: Arguments could be made that the claimed formulation was obvious to a person skilled in the art, given the existing knowledge of drug formulation and the properties of upadacitinib.

The patent's strength lies in its specificity regarding the therapeutic use (RA) and the inclusion of key excipient classes in an oral dosage form. Its limitations are found in the specificity of the excipients in dependent claims and the potential for alternative formulations or challenges to its validity.

Key Takeaways

• U.S. Patent 10,525,053 protects a method of treating rheumatoid arthritis using an oral pharmaceutical composition containing upadacitinib.
• The patent's claims specify the inclusion of a disintegrant, lubricant, binder, and diluent within the oral dosage form.
• Dependent claims further define these excipients, naming crospovidone, magnesium stearate, and hydroxypropyl cellulose as specific examples.
• This patent is linked to AbbVie Inc.'s JAK inhibitor, upadacitinib (Rinvoq), and its use for RA treatment.
• The patent landscape for upadacitinib and JAK inhibitors is dense with overlapping patents covering compounds, synthesis, formulations, and methods of use.
• Patent 10,525,053 extends market exclusivity for a specific oral formulation and method of treating RA, impacting generic and biosimilar market entry until its expiration on December 31, 2036.
• Generic manufacturers must navigate this patent to avoid infringement, potentially by designing around the specified excipients or challenging the patent's validity.

FAQs

1. Does Patent 10,525,053 cover the upadacitinib molecule itself? No, the patent primarily claims a method of treating rheumatoid arthritis using an oral pharmaceutical composition containing upadacitinib. It does not claim the upadacitinib molecule itself, which would be covered by separate compound patents.

2. What are the main excipients specified in the patent's claims for the oral composition? The patent claims require the presence of a disintegrant, a lubricant, a binder, and a diluent. Dependent claims specifically mention crospovidone as a disintegrant, magnesium stearate as a lubricant, and hydroxypropyl cellulose as a binder.

3. When does U.S. Patent 10,525,053 expire, and what is its significance for generic drug entry? The patent expires on December 31, 2036. This expiration date defines the period during which generic manufacturers are restricted from marketing a product using the specific method and oral formulation claimed in the patent for the treatment of rheumatoid arthritis.

4. Can a generic manufacturer bypass this patent by using a different route of administration for upadacitinib? Yes, if other patents do not cover those alternative routes of administration, a generic manufacturer could potentially develop and market upadacitinib via a different route (e.g., injection) without infringing this specific patent, as it is limited to an "oral pharmaceutical composition."

5. What legal strategies might a generic company employ to challenge Patent 10,525,053? A generic company could challenge the patent's validity by arguing that the claimed invention was not novel or was obvious at the time of filing. They might also seek to demonstrate that their proposed product and method of use do not infringe the patent's claims, for example, by using significantly different excipients or formulations not covered by the dependent claims.

Citations

[1] AbbVie Inc. (2019). Method of treating rheumatoid arthritis. U.S. Patent 10,525,053. Washington, D.C.: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 10,525,053

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 10,525,053

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2003247876
Canada	2491572
Canada	2569958
Canada	2916869
Cyprus	1119831