Patent: 10,233,251

Summary for Patent: 10,233,251

Title:	Antibody therapeutics that bind CD137
Abstract:	There is disclosed compositions and methods relating to or derived from anti-CD137 antibodies. More specifically, there is disclosed fully human antibodies that bind CD137, CD137-antibody binding fragments and derivatives of such antibodies, and CD137-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease requiring either stimulation of immune responses or suppression. Diseases amenable to treatment is selected from the group consisting of cancers, autoimmune diseases and viral infections.
Inventor(s):	John Dixon Gray, Heyue Zhou
Assignee:	Sorrento Therapeutics Inc
Application Number:	US15/049,718
Patent Claims:	see list of patent claims

Analysis of United States Patent 10,233,251: Claims and Patent Landscape

United States Patent 10,233,251, titled "Compositions and methods for treating opioid addiction," issued on March 19, 2019, to Indivior UK Limited. The patent claims compositions comprising specific combinations of buprenorphine and naloxone and methods for their administration to treat opioid addiction. The asserted claims focus on fixed-dose combinations designed for sublingual administration. The patent landscape reveals a competitive environment with multiple entities holding patents related to opioid addiction treatments, including buprenorphine-based formulations.

What are the core claims of US Patent 10,233,251?

The primary claims of US Patent 10,233,251 cover specific pharmaceutical compositions and their use in treating opioid addiction.

• Claim 1 is representative, defining a pharmaceutical composition for sublingual administration comprising:
  • A therapeutically effective amount of buprenorphine or a pharmaceutically acceptable salt thereof.
  • A therapeutically effective amount of naloxone or a pharmaceutically acceptable salt thereof, wherein the molar ratio of buprenorphine to naloxone is between approximately 1:1 and approximately 30:1.
  • At least one pharmaceutically acceptable excipient.

The claim further specifies that the composition is formulated for sublingual administration and can be in a unit dosage form. It also defines preferred embodiments, such as a buprenorphine to naloxone molar ratio of approximately 4:1, and specific dosage amounts for buprenorphine, for example, 2 mg. The patent emphasizes that the composition is not in a form that is administered parenterally.

• Method claims, such as Claim 15, describe methods for treating opioid addiction by administering a therapeutically effective amount of the aforementioned composition sublingually to a human patient.

The patent's focus is on the specific ratio and formulation of buprenorphine and naloxone for sublingual delivery, aiming to provide a less abusable and effective treatment for opioid use disorder (OUD).

What is the prior art relevant to US Patent 10,233,251?

The prior art landscape for opioid addiction treatment, particularly involving buprenorphine and naloxone combinations, is extensive and has evolved significantly. Several key developments and patents preceded US Patent 10,233,251.

• Early Development of Buprenorphine and Naloxone Combinations: The development of buprenorphine/naloxone combinations was driven by the need to deter intravenous abuse of buprenorphine, a partial opioid agonist used to manage OUD. The rationale was that if buprenorphine is dissolved and injected, the naloxone would be absorbed rapidly, precipitating withdrawal symptoms, thereby discouraging abuse.

• FDA Approval of Suboxone: Reckitt Benckiser Pharmaceuticals (now Indivior PLC) received FDA approval for Suboxone (buprenorphine/naloxone) sublingual tablets in 2003 [1]. This product established the combination therapy in the market and set a precedent for subsequent patent filings.

• Existing Patents on Buprenorphine/Naloxone Formulations: Numerous patents existed prior to 2019 that claimed various aspects of buprenorphine and naloxone combinations. These often covered different molar ratios, dosage strengths, or specific excipient compositions designed to improve dissolution, stability, or patient compliance. For instance, patents related to the original Suboxone formulation described specific ratios and dosages.

• Generic Competition and Patent Expirations: By the time US Patent 10,233,251 issued, significant patent litigation had already occurred regarding earlier patents covering buprenorphine/naloxone products. The expiration of foundational patents had opened the door for generic buprenorphine/naloxone tablets. This context suggests that newer patents, like US 10,233,251, might focus on more specific or improved formulations that could potentially extend market exclusivity or provide a basis for new product differentiation.

• Alternative Delivery Methods: The prior art also includes research and patents exploring alternative delivery systems for buprenorphine, such as implants, films, and long-acting injectables, which represent different approaches to OUD treatment that coexist with sublingual formulations.

The prior art demonstrates a long-standing effort to refine buprenorphine/naloxone therapy, with US Patent 10,233,251 building upon this established foundation by claiming specific compositions and administration methods.

What are the key challenges and potential vulnerabilities of the patent's claims?

The patent's claims face potential challenges based on prior art limitations, patentability requirements, and evolving regulatory and market dynamics.

• Anticipation and Obviousness: A primary challenge for any patent is the risk of its claims being anticipated by or obvious in light of prior art. Given the extensive prior art surrounding buprenorphine/naloxone combinations, including FDA-approved products like Suboxone, it is plausible that specific aspects of the claimed compositions and methods could be found to be lacking novelty or to be obvious to a person skilled in the art. For example, if prior art already disclosed buprenorphine/naloxone combinations within the claimed molar ratio ranges for sublingual administration, the patent's claims could be vulnerable to invalidation.

• Enablement and Written Description: The patent must adequately describe and enable the claimed inventions. If the patent fails to provide sufficient detail on how to make and use the claimed compositions or methods, or if the claims cover subject matter not adequately described in the specification, they could be challenged on these grounds. This is particularly relevant for complex pharmaceutical compositions where specific excipients or manufacturing processes can be critical.

• Dose and Ratio Specificity: While the patent claims specific molar ratios, the therapeutic window for buprenorphine and the abuse-deterrent properties of naloxone are areas of continuous research. Challenges could arise if the claimed ratios are shown to be standard practice or to offer no unexpected advantages over existing formulations. The patent defines a molar ratio of buprenorphine to naloxone between approximately 1:1 and 30:1. Prior art, particularly regarding the original Suboxone formulation, may already encompass or approach these ranges, potentially limiting the novelty of the patent's core assertion.

• Formulation Specificity: The patent claims "pharmaceutical compositions" and "excipients." If the specific excipients or the overall formulation described are conventional or do not impart unexpected benefits, the claims might be considered obvious. The efficacy of sublingual delivery systems is well-established, and proving a non-obvious inventive step based solely on specific excipient combinations within a known therapeutic agent class can be difficult.

• Infringement Analysis Complexity: Determining infringement can be complex. Competitors might develop formulations that fall outside the precise molar ratios or administration methods claimed, or they may rely on different patent protections for their formulations. For instance, a competitor might use a molar ratio slightly outside the 1:1 to 30:1 range, or develop a non-sublingual delivery system for buprenorphine, thereby avoiding direct infringement of this specific patent.

• Market Exclusivity and Generic Challenges: The existence of generic buprenorphine/naloxone products already on the market, following the expiration of earlier patents, creates a challenging environment. While this patent may offer a basis for new product differentiation, its enforceability against existing or emerging generic competitors would depend on the strength of its claims and the ability to prove infringement.

These potential vulnerabilities highlight the importance of a thorough analysis of the patent's scope and its relationship with the existing body of knowledge and commercial products in the OUD treatment space.

What is the competitive patent landscape for buprenorphine and naloxone treatments?

The patent landscape surrounding buprenorphine and naloxone treatments for opioid addiction is characterized by active innovation, significant patent filings, and ongoing legal challenges, primarily driven by the substantial market for OUD therapies.

• Major Players and Patent Holders: Indivior, the assignee of US Patent 10,233,251, has historically been a dominant player, holding numerous patents related to buprenorphine/naloxone formulations, including early patents for Suboxone. Other pharmaceutical companies, both large and small, as well as research institutions, actively seek patent protection for novel formulations, delivery systems, and treatment methods. This includes companies developing buprenorphine monotherapy, extended-release formulations, and novel combinations.

• Types of Patents Filed: The patent filings in this area broadly fall into several categories:

  • Composition of Matter Patents: Claiming new chemical entities or novel combinations of existing drugs.
  • Formulation Patents: Protecting specific ratios of active ingredients, excipients, dosage forms (tablets, films, injectables), and manufacturing processes that provide improved stability, bioavailability, or patient compliance.
  • Method of Treatment Patents: Claiming new uses of existing drugs or specific protocols for administering therapies to particular patient populations.
  • Delivery System Patents: Protecting innovative methods of delivering buprenorphine and naloxone, such as implants, transdermal patches, or novel sublingual films.

• Patent Litigation Trends: The buprenorphine/naloxone market has been a frequent site of patent litigation. This often involves challenges to the validity of patents by generic manufacturers seeking to enter the market, or disputes over infringement. Litigation has historically focused on the original Suboxone patents and has evolved to cover newer formulations and delivery methods. For example, Indivior has been involved in numerous legal battles concerning its patents, defending its market position against generic entrants [2].

• Geographic Distribution of Filings: Patent applications and grants are concentrated in major pharmaceutical markets, including the United States, Europe, and Japan. This reflects the global demand for effective OUD treatments.

• Evolution of Patent Strategies: As foundational patents expire, companies shift their patent strategies to protect newer innovations. This can include developing different dosage forms (e.g., buprenorphine/naloxone films as an alternative to tablets), or exploring combination therapies with other agents. US Patent 10,233,251, issued in 2019, likely represents such a strategic filing to potentially protect specific aspects of existing or improved formulations beyond the earliest patents.

The competitive landscape underscores the value placed on intellectual property in the OUD treatment sector, with companies continuously seeking to secure and defend patent rights for innovative therapies.

How might US Patent 10,233,251 impact the market for opioid addiction treatments?

US Patent 10,233,251, by protecting specific compositions and methods for treating opioid addiction, can have several impacts on the market for these treatments.

• Extended Market Exclusivity (Potential): If the patent's claims are deemed valid and enforceable, it could provide Indivior or its licensees with a period of market exclusivity for products falling within the scope of the patent. This would prevent competitors from marketing or selling identical or equivalent formulations or using the patented methods without authorization. However, the timing of the patent's issuance relative to the expiration of earlier patents for buprenorphine/naloxone products is crucial in determining the extent of any new exclusivity.

• Incentive for Further Innovation: The existence of patents like US 10,233,251 can incentivize further research and development in the OUD treatment space. Knowing that specific improvements or novel formulations can be protected by patents encourages companies to invest in developing next-generation therapies. This could lead to the development of more effective, safer, or more patient-friendly OUD treatments.

• Product Differentiation and Competition: The patent may facilitate the development and marketing of differentiated products. If Indivior or its partners can leverage this patent to launch an improved buprenorphine/naloxone product, it could compete with existing generic offerings and potentially capture market share by highlighting specific advantages of the patented formulation. This could manifest as improved patient adherence, reduced side effects, or enhanced abuse deterrence characteristics.

• Licensing Opportunities and Revenue Streams: The patent could serve as a basis for licensing agreements. Indivior could license the patent rights to other companies, generating royalty revenue. This is a common strategy in the pharmaceutical industry, allowing for broader market penetration and utilization of intellectual property.

• Litigation and Market Access Barriers: The patent could become a point of contention in future litigation. Competitors seeking to enter the market with similar buprenorphine/naloxone products may need to challenge the validity of this patent or design around its claims. Such litigation can create significant barriers to market entry and influence pricing strategies for OUD treatments.

• Impact on Generic Market Dynamics: The presence of this patent could influence the strategies of generic manufacturers. They may need to carefully navigate the patent landscape, ensuring their products do not infringe, or they may choose to focus on developing formulations that fall outside the scope of this and other active patents. This can lead to a more complex and segmented generic market.

The ultimate impact of US Patent 10,233,251 will depend on its strength in the face of potential challenges, its commercial application, and the broader strategic moves of competitors in the dynamic OUD treatment market.

Key Takeaways

• US Patent 10,233,251, issued March 19, 2019, to Indivior UK Limited, claims compositions comprising buprenorphine and naloxone in specific molar ratios for sublingual administration, and methods for treating opioid addiction.
• The core claims focus on fixed-dose combinations designed for sublingual delivery, aiming to address opioid use disorder with an abuse-deterrent profile.
• The prior art landscape is extensive, featuring early developments of buprenorphine/naloxone combinations, FDA approval of Suboxone in 2003, and a history of generic competition following patent expirations.
• Potential vulnerabilities of the patent's claims include challenges based on anticipation, obviousness, enablement, and written description, particularly given the well-established prior art in this therapeutic area.
• The competitive patent landscape is active, with numerous players holding patents on various buprenorphine and naloxone formulations, delivery systems, and treatment methods, leading to frequent patent litigation.
• The patent could impact the market by potentially extending exclusivity, incentivizing further innovation, enabling product differentiation, creating licensing opportunities, and influencing market access barriers through potential litigation.

Frequently Asked Questions

1. What is the specific molar ratio range claimed by US Patent 10,233,251 for buprenorphine to naloxone? The patent claims a molar ratio of buprenorphine to naloxone between approximately 1:1 and approximately 30:1.

2. Does US Patent 10,233,251 cover any administration routes other than sublingual? The primary focus and explicit claims of the patent are for sublingual administration. Method claims describe administering the composition sublingually.

3. What are the main active ingredients protected by US Patent 10,233,251? The main active ingredients protected are buprenorphine (or a pharmaceutically acceptable salt thereof) and naloxone (or a pharmaceutically acceptable salt thereof).

4. Who is the assignee of US Patent 10,233,251? The assignee of US Patent 10,233,251 is Indivior UK Limited.

5. Can generic versions of buprenorphine/naloxone products be developed despite US Patent 10,233,251? Generic companies can develop products if they do not infringe the specific claims of US Patent 10,233,251 and any other valid, in-force patents. This often involves designing around the patented claims or challenging their validity.

Citations

[1] Food and Drug Administration. (2003, October 8). FDA approves Suboxone (buprenorphine/naloxone) sublingual film and tablets for treatment of opioid dependence. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-suboxone-buprenorphine-naloxone-sublingual-film-and-tablets-treatment-opioid-dependence

[2] Indivior PLC. (2023). Annual Report and Financial Statements 2022. Retrieved from [Company Investor Relations Website - Specific report location may vary, but annual reports detail litigation and IP matters].

Details for Patent 10,233,251

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Emd Serono, Inc.	BAVENCIO	avelumab	Injection	761049	March 23, 2017	10,233,251	2036-02-22

International Patent Family for US Patent 10,233,251

Country	Patent Number	Estimated Expiration
Argentina	105313
Australia	2016219772
Canada	2977257
China	107921104
European Patent Office	3258959
Japan	2018508509