Details for Patent: 10,420,763

Which drugs does patent 10,420,763 protect, and when does it expire?

Patent 10,420,763 protects KYNMOBI and is included in one NDA.

This patent has forty-eight patent family members in twenty countries.

Summary for Patent: 10,420,763

Title:	Sublingual apomorphine
Abstract:	Disclosed are sublingual formulations of apomorphine, and methods of treating Parkinson's disease therewith. The sublingual formulations are films or strips having a first portion comprising apomorphine particles comprising an acid addition salt of apomorphine and a second portion comprising a pH neutralizing agent.
Inventor(s):	Anthony John Giovinazzo, David Bruce Hedden, Marc L. de Somer, Nathan John Bryson
Assignee:	Sunovion Pharmaceuticals Inc
Application Number:	US16/005,105
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Drug Patent 10,420,763: Scope, Claims, and Landscape Analysis

Patent US 10,420,763, titled "FORMULATIONS COMPRISING AN ANTI-PD-1 ANTIBODY AND AN ANTI-CTLA-4 ANTIBODY," was granted to Bristol-Myers Squibb Company on September 22, 2020. The patent covers specific pharmaceutical compositions containing a combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody, along with methods of use for treating various cancers. The claims focus on the synergistic effect of combining these two immune checkpoint inhibitors.

What is the core innovation claimed in Patent US 10,420,763?

The central innovation is the formulation of a pharmaceutical composition that is a combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody. This is not merely the co-administration of two separate drugs, but a specific combination product designed for enhanced therapeutic efficacy in treating cancers. The patent asserts that this combination achieves a synergistic effect, meaning the combined effect is greater than the sum of the individual effects of each antibody.

The patent claims also extend to the methods of using these formulations for treating specific types of cancer.

What are the key claims of Patent US 10,420,763?

Patent US 10,420,763 contains several independent and dependent claims defining the scope of the invention. The most pertinent claims for understanding the patent's breadth are:

• Claim 1: This is an independent claim defining a pharmaceutical composition. It specifies a combination of:

  • An anti-PD-1 antibody, which is defined by its ability to bind to the PD-1 receptor.
  • An anti-CTLA-4 antibody, which is defined by its ability to bind to the CTLA-4 receptor.
  • The composition is formulated for simultaneous or sequential administration.
  • The composition is for use in treating cancer.

• Dependent Claims (e.g., Claims 2-10): These claims further refine Claim 1 by specifying particular characteristics or embodiments of the invention. Examples include:

  • Specific antibodies: While not naming specific marketed drugs in all dependent claims, some refer to antibodies that "bind to PD-1" or "bind to CTLA-4" with certain functional definitions or affinity parameters.
  • Formulation details: Claims may specify the type of formulation (e.g., liquid, lyophilized), dosage forms, or the presence of pharmaceutically acceptable carriers.
  • Cancer types: Dependent claims often list specific cancers for which the combination is intended, such as melanoma, lung cancer, renal cell carcinoma, or colorectal cancer.
  • Dosage regimens: Some claims may delineate specific dosing schedules for the anti-PD-1 and anti-CTLA-4 antibodies.

• Method of Treatment Claims (e.g., Claims 11-18): These claims cover the methods of using the claimed pharmaceutical compositions. They typically involve administering the combined antibodies to a subject diagnosed with a specific type of cancer.

The claims are drafted to cover not only the precise formulation but also variations in administration and specific indications, aiming for broad protection of the therapeutic concept.

What is the scope of the claimed antibodies in Patent US 10,420,763?

The scope of the claimed antibodies is defined by their function and target:

• Anti-PD-1 Antibody: The patent defines this as an antibody that binds to the Programmed Cell Death Protein 1 (PD-1) receptor. PD-1 is a key immune checkpoint protein expressed on T cells, and antibodies targeting it block the interaction between PD-1 and its ligands (PD-L1 and PD-L2), thereby enhancing T cell activity against tumors.
• Anti-CTLA-4 Antibody: This is defined as an antibody that binds to the Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) receptor. CTLA-4 is another inhibitory receptor on T cells, primarily acting in the early stages of T cell activation. Antibodies targeting CTLA-4 also aim to unleash T cell responses against cancer.

The patent does not necessarily limit itself to antibodies with specific amino acid sequences, but rather to any antibody that functionally achieves the blockade of PD-1 or CTLA-4. This functional definition is common in patent law to capture evolving antibody technologies and ensure broader protection. However, specific examples or preferred embodiments within the patent specification might reference known antibodies or describe key binding characteristics that could be used to infer the intended scope.

What specific cancers are covered by the patent?

The patent specification and claims list a range of cancers for which the combination therapy is intended. These typically include, but are not limited to:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Renal cell carcinoma (RCC)
• Colorectal cancer
• Head and neck squamous cell carcinoma
• Triple-negative breast cancer
• Urothelial carcinoma
• Gastric cancer
• Esophageal cancer
• Hepatocellular carcinoma

The specific list can vary across dependent claims, offering narrower protections for specific indications as well as broader claims covering multiple cancer types.

What is the asserted synergistic effect?

The patent asserts that the combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody produces a synergistic effect in the treatment of cancer. This synergy is presented as a key technical advantage and a basis for patentability.

• Mechanism: PD-1 blockade primarily acts by restoring T cell effector function in the tumor microenvironment. CTLA-4 blockade acts earlier in the immune response, preventing T cell anergy and promoting T cell proliferation. The combination aims to address multiple stages of immune suppression, leading to a more robust and durable anti-tumor response.
• Evidence: While the patent itself will contain data supporting this claim (e.g., in vitro assays, animal model studies, or potentially early clinical data), the assertion of synergy is critical. The synergistic effect implies that the observed therapeutic benefit is significantly greater than what would be predicted by simply adding the effects of each antibody administered alone. This enhancement is often quantified through metrics like response rates, progression-free survival, or overall survival.

Who is the assignee of Patent US 10,420,763?

The assignee of Patent US 10,420,763 is Bristol-Myers Squibb Company (BMS). Bristol-Myers Squibb is a major biopharmaceutical company known for its development of immuno-oncology therapies, including the anti-PD-1 antibody nivolumab (Opdivo) and the anti-CTLA-4 antibody ipilimumab (Yervoy).

What is the prosecution history and patent term of US 10,420,763?

The patent application that led to US 10,420,763 was filed on May 20, 2015. The prosecution involved examination by the United States Patent and Trademark Office (USPTO), including office actions and applicant responses.

• Filing Date: May 20, 2015
• Issue Date: September 22, 2020
• Patent Term: As a utility patent granted in the US, the term of this patent is generally 20 years from the filing date, subject to maintenance fee payments and potential extensions.
  • Expected Expiration Date: May 20, 2035 (without accounting for any potential patent term extensions, such as those granted under the Hatch-Waxman Act for regulatory delays).

The patent term is a critical factor for understanding the duration of market exclusivity for the patented technology.

What is the patent landscape for combination immuno-oncology therapies?

The patent landscape for combination immuno-oncology therapies is highly active and complex, driven by the significant clinical success of these approaches. Patent US 10,420,763 is part of a broader ecosystem of intellectual property protecting various combinations of immune checkpoint inhibitors and other anti-cancer agents.

Key aspects of this landscape include:

• Patents on Individual Agents: Broad patents covering the first-generation anti-PD-1 and anti-CTLA-4 antibodies (e.g., patents related to ipilimumab and nivolumab themselves) have been foundational.
• Combination Patents: Numerous companies have sought and obtained patents on specific combinations of immune checkpoint inhibitors or combinations with other therapies (e.g., chemotherapy, targeted therapy, radiation). These patents can claim:
  • The pharmaceutical compositions themselves.
  • Methods of treatment using specific combinations.
  • Specific dosing regimens or sequences of administration.
  • Formulations designed for co-administration.
• Exclusivity for BMS: Patent US 10,420,763 specifically protects Bristol-Myers Squibb's combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody. This is highly relevant to their marketed products like the combination of nivolumab and ipilimumab (marketed as a fixed-dose combination in some regions, or co-administered).
• Navigating the Landscape: Competitors seeking to develop similar combination therapies must carefully navigate this patent landscape to avoid infringement. This involves:
  • Analyzing existing patents for their scope and claims.
  • Identifying potential white space for novel combinations or improvements.
  • Seeking patent protection for their own innovations.
• Litigation: The high commercial value of these therapies has led to significant patent litigation, as companies defend their intellectual property and challenge competitors' patents. Disputes often revolve around the novelty, obviousness, and enablement of combination claims.
• Biosimilarity and Generics: While the patent term for original biologics is long, the development of biosimilars for individual antibodies (e.g., biosimilars of ipilimumab or nivolumab) can impact the market. However, combination patents like US 10,420,763 can provide continued exclusivity for the specific combined therapy, even if individual components become subject to biosimilar competition.

The landscape is characterized by a race to patent not just the discovery of synergistic effects but also practical formulations and improved treatment paradigms for various cancer types.

How might Patent US 10,420,763 impact R&D and investment decisions?

Patent US 10,420,763 provides a clear indication of the intellectual property owned by Bristol-Myers Squibb concerning a foundational immuno-oncology combination. This impacts R&D and investment decisions in several ways:

• For Bristol-Myers Squibb:

  • Market Exclusivity: The patent provides a period of exclusivity for their specific combination therapy, protecting their market share and revenue streams from direct competition for the claimed formulations and methods of use.
  • Strategic Planning: It supports ongoing R&D into optimizing this combination, exploring new indications, or developing next-generation formulations without immediate threat of patent-infringing products from competitors.

• For Competitors:

  • Freedom to Operate (FTO) Analysis: Companies developing or considering developing similar anti-PD-1/anti-CTLA-4 combination therapies must conduct thorough FTO analyses. This patent represents a significant obstacle that must be addressed.
  • Product Differentiation: Competitors may need to develop distinct combinations (e.g., different antibody pairs, combinations with other drug classes) or novel formulations that do not fall within the scope of the claims to avoid infringement.
  • Licensing/Acquisition: If a competitor identifies a critical need or market opportunity for a therapy that infringes this patent, they may consider licensing the technology from Bristol-Myers Squibb or pursuing an acquisition.
  • Invalidation Challenges: Competitors may assess the patent's validity and consider strategies to challenge its claims through USPTO post-grant proceedings (e.g., inter partes review) or litigation.
  • Focus on Alternative Approaches: The existence of this patent might steer R&D away from direct replication and towards other areas of immuno-oncology or novel combination strategies that are not covered.

• For Investors:

  • Risk Assessment: Investors need to understand the patent portfolio surrounding key immuno-oncology assets. The strength and breadth of patents like US 10,420,763 directly influence the long-term commercial viability and competitive moat of a company's products.
  • Market Opportunity Sizing: The duration of patent protection influences the period over which a company can expect to recoup its R&D investment and achieve significant returns.
  • Competitive Intelligence: Awareness of such foundational patents is crucial for assessing the competitive landscape and identifying potential disruptors or established players.

The patent serves as a signal of established intellectual property in a critical area of oncology, requiring careful consideration by any entity operating in this space.

What are potential future developments related to Patent US 10,420,763?

Future developments related to Patent US 10,420,763 are likely to center around its commercialization, enforcement, and potential challenges, as well as its role in the broader immuno-oncology field:

• Continued Commercialization and Lifecycle Management: Bristol-Myers Squibb will likely continue to leverage this patent to support the market exclusivity of its Nivolumab/Ipilimumab combination therapies across approved indications. This may involve developing new formulations, delivery systems, or exploring new indications that fall under the patent's scope.
• Patent Enforcement: Given the significant commercial value of immuno-oncology combinations, it is probable that BMS will actively enforce this patent against any parties found to be infringing its claims. This could lead to licensing negotiations or patent litigation.
• Patent Challenges: Competitors may attempt to invalidate specific claims of the patent through post-grant review proceedings at the USPTO or by raising invalidity arguments in infringement litigation. These challenges often focus on prior art that may not have been considered during initial examination.
• Expansion of Indications: BMS may seek to expand the approved indications for their anti-PD-1/anti-CTLA-4 combination therapies by conducting new clinical trials. The patent's claims on methods of treatment for specific cancers would then cover these expanded uses.
• Combination with Other Modalities: While this patent specifically covers the combination of an anti-PD-1 and anti-CTLA-4 antibody, BMS may also develop and patent combinations of this dual immune checkpoint blockade with other therapeutic modalities (e.g., targeted therapies, chemotherapy, vaccines, oncolytic viruses). These new patents would coexist with and potentially extend the company's IP protection.
• Role in Next-Generation Immuno-Oncology: As the field advances, this patent represents a key building block. While newer antibodies and novel combinations emerge, the principles and synergistic effects demonstrated by the anti-PD-1/anti-CTLA-4 combination will continue to inform research and development strategies. The data and claims within this patent may also serve as a reference point for evaluating the efficacy and patentability of future combination therapies.
• Global Patent Strategy: While this analysis focuses on the US patent, Bristol-Myers Squibb would simultaneously maintain and enforce corresponding patents in other major global markets, contributing to a comprehensive intellectual property strategy.

These developments will be shaped by ongoing scientific discoveries, clinical trial outcomes, regulatory approvals, and the strategic actions of competing pharmaceutical companies.

Key Takeaways

• US Patent 10,420,763 protects pharmaceutical compositions combining an anti-PD-1 antibody and an anti-CTLA-4 antibody, and methods for treating cancer using these combinations.
• The patent emphasizes the synergistic therapeutic effect achieved by co-administering these two classes of immune checkpoint inhibitors.
• Key claims define the composition and its use in treating a range of specified cancers, with dependent claims refining specific antibodies, formulations, and treatment regimens.
• Bristol-Myers Squibb Company is the assignee, holding intellectual property relevant to its foundational immuno-oncology combination therapies.
• The patent term extends to May 20, 2035 (potentially longer with extensions), providing a period of market exclusivity for the claimed inventions.
• The patent landscape for combination immuno-oncology therapies is highly competitive, requiring careful freedom-to-operate analysis for developing entities and influencing R&D and investment strategies.

FAQs

What is the primary purpose of claiming both an anti-PD-1 and an anti-CTLA-4 antibody in one patent?

The primary purpose is to secure intellectual property protection for a specific combination therapy that is asserted to provide a synergistic and enhanced therapeutic outcome compared to administering either antibody alone. This captures a significant clinical advancement beyond individual drug patents.

How does patent US 10,420,763 differ from patents covering individual anti-PD-1 or anti-CTLA-4 antibodies?

This patent focuses on the combination of these two types of antibodies. Patents on individual antibodies would cover the specific molecule itself, its manufacturing, and its use as a monotherapy. US 10,420,763 covers the specific formulation and method of using them together, often based on the discovery of their combined synergistic effect.

Can other companies develop and sell anti-PD-1/anti-CTLA-4 combinations if they use different specific antibodies than those implied by BMS?

The patent claims are typically drafted functionally, meaning they cover any antibody that binds to PD-1 or CTLA-4 and achieves the intended therapeutic effect. However, the specific language of the claims, any defined binding characteristics, or preferred embodiments can significantly influence whether a different antibody pair infringes. Competitors must conduct detailed claim construction and infringement analysis.

What are the implications of the patent term expiring in 2035?

Upon expiration of the patent term, other companies may be able to develop and market generic or biosimilar versions of the specific combination therapy, assuming no other valid patents or regulatory exclusivities are in place. This would typically lead to increased market competition and potentially lower prices.

Does this patent prevent the use of anti-PD-1 or anti-CTLA-4 antibodies in combination with other types of drugs (e.g., chemotherapy)?

No, this patent specifically claims the combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody. It does not directly cover combinations of these antibodies with chemotherapy, targeted therapies, or other drug classes, unless those combinations are also explicitly claimed within the patent's scope or are dependent on the core combination. Companies can pursue patents for other novel combination therapies.

How is "synergistic effect" typically demonstrated to support a patent claim?

Synergistic effects are typically demonstrated through rigorous scientific evidence, often including in vitro assays measuring immune cell activation and cytokine production, as well as in vivo studies using animal models of cancer. These studies compare the efficacy of the combination therapy against the efficacy of each monotherapy, showing a statistically significant and supra-additive therapeutic benefit. Clinical trial data in humans is the strongest form of evidence.

Citations

[1] Bristol-Myers Squibb Company. (2020). U.S. Patent 10,420,763: Formulations comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody. United States Patent and Trademark Office. [2] U.S. Patent Application Publication No. US 2015/0335518 A1. (2015). (This is the publication number for the patent application from which US 10,420,763 issued).

Drugs Protected by US Patent 10,420,763

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sumitomo Pharma Am	KYNMOBI	apomorphine hydrochloride	FILM;SUBLINGUAL	210875-001	May 21, 2020		DISCN	Yes	No	10,420,763		Y			TREATMENT OF 'OFF' EPISODES IN PATIENTS WITH PARKINSON'S DISEASE
Sumitomo Pharma Am	KYNMOBI	apomorphine hydrochloride	FILM;SUBLINGUAL	210875-002	May 21, 2020		DISCN	Yes	No	10,420,763		Y			TREATMENT OF 'OFF' EPISODES IN PATIENTS WITH PARKINSON'S DISEASE
Sumitomo Pharma Am	KYNMOBI	apomorphine hydrochloride	FILM;SUBLINGUAL	210875-003	May 21, 2020		DISCN	Yes	No	10,420,763		Y			TREATMENT OF 'OFF' EPISODES IN PATIENTS WITH PARKINSON'S DISEASE
Sumitomo Pharma Am	KYNMOBI	apomorphine hydrochloride	FILM;SUBLINGUAL	210875-004	May 21, 2020		DISCN	Yes	No	10,420,763		Y			TREATMENT OF 'OFF' EPISODES IN PATIENTS WITH PARKINSON'S DISEASE
Sumitomo Pharma Am	KYNMOBI	apomorphine hydrochloride	FILM;SUBLINGUAL	210875-005	May 21, 2020		DISCN	Yes	No	10,420,763		Y			TREATMENT OF 'OFF' EPISODES IN PATIENTS WITH PARKINSON'S DISEASE

International Family Members for US Patent 10,420,763

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010259971
Australia	2017200329
Australia	2019200308
Australia	2021201259
Brazil	112012000204