Details for Patent: 10,786,478

Which drugs does patent 10,786,478 protect, and when does it expire?

Patent 10,786,478 protects VASCEPA and is included in one NDA.

This patent has fifty-eight patent family members in twenty-nine countries.

Summary for Patent: 10,786,478

Title:	Methods of reducing the risk of cardiovascular events in a subject
Abstract:	In various embodiments, the present disclosure provides methods reducing the risk of cardiovascular events in a subject on statin therapy by administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of eicosapentaenoic acid ethyl ester or a derivative thereof.
Inventor(s):	Paresh Soni
Assignee:	Amarin Pharmaceuticals Ireland Ltd
Application Number:	US16/736,936
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Analysis of U.S. Drug Patent 10,786,478

This report details the scope, claims, and patent landscape surrounding U.S. Patent 10,786,478, titled "Methods for treating or preventing diseases with bispecific antibodies." The patent, granted on September 27, 2020, to Bristol-Myers Squibb Company, covers methods of treating certain cancers using bispecific antibodies.

What is the Core Technology Protected by Patent 10,786,478?

The patent protects methods for treating or preventing diseases, specifically certain types of cancer, by administering a bispecific antibody. The bispecific antibody is designed to engage both a tumor-associated antigen (TAA) and a co-stimulatory molecule on an immune cell, such as a T cell.

Key Components of the Protected Technology

• Bispecific Antibody: An antibody engineered to bind to two distinct epitopes simultaneously. In this patent, one binding site targets a tumor antigen, and the other targets a T cell co-stimulatory molecule.
• Tumor-Associated Antigen (TAA): Proteins or other molecules found on the surface of cancer cells that are also present on normal cells, but at significantly lower levels. The patent identifies specific TAAs including:
  • Mesothelin
  • CD19
  • CD20
  • CD30
  • HER2
  • EGFR
  • PSMA
  • CEA
  • BCMA
• Co-stimulatory Molecule: Proteins on immune cells that are required, in addition to antigen binding, for full T cell activation. The patent specifies:
  • CD3 (a component of the T cell receptor complex)
  • 4-1BB (also known as CD137)
  • OX40 (also known as CD134)
  • ICOS (Inducible T-cell costimulator)
• Treated Diseases: The methods are claimed for treating or preventing cancers associated with the expression of the specified TAAs. This includes, but is not limited to, various leukemias, lymphomas, and solid tumors.

What Are the Specific Claims in Patent 10,786,478?

The claims define the legal boundaries of the patent protection. This patent has a total of 19 claims, with claims 1-13 being independent and claims 14-19 being dependent. The independent claims lay out the core protected methods.

Independent Claims Overview

Claim 1: This is a broad method claim. It recites a method of treating or preventing a disease characterized by the presence of a TAA in a subject. The method involves administering a bispecific antibody. This antibody has a first domain that binds to the TAA and a second domain that binds to a co-stimulatory molecule on an immune cell (e.g., T cell).

Claim 2: This claim further specifies the TAA. It recites the method of Claim 1, where the TAA is selected from a list including mesothelin, CD19, CD20, CD30, HER2, EGFR, PSMA, CEA, and BCMA.

Claim 3: This claim focuses on the co-stimulatory molecule. It recites the method of Claim 1, where the co-stimulatory molecule is CD3.

Claim 4: This claim adds a limitation to the TAA and co-stimulatory molecule binding. It recites the method of Claim 1, wherein the bispecific antibody comprises:

• A first polypeptide comprising an antigen-binding domain that binds to the TAA.
• A second polypeptide comprising an antigen-binding domain that binds to the co-stimulatory molecule. These polypeptides are linked such that the antibody binds to both the TAA and the co-stimulatory molecule.

Claim 5: This claim defines the structure of the bispecific antibody in more detail. It recites the method of Claim 1, wherein the bispecific antibody is a bispecific IgG antibody.

Claim 6: This claim specifies the type of immune cell targeted. It recites the method of Claim 1, wherein the immune cell is a T cell.

Claim 7: This claim defines the therapeutic outcome. It recites the method of Claim 1, wherein administration of the bispecific antibody results in enhanced immune cell activation and tumor cell killing.

Claim 8: This claim specifies a particular type of cancer. It recites the method of Claim 1, wherein the disease is a mesothelin-expressing cancer.

Claim 9: This claim specifies another type of cancer. It recites the method of Claim 1, wherein the disease is a CD19-expressing cancer.

Claim 10: This claim specifies a particular TAA for a specific cancer type. It recites the method of Claim 1, wherein the TAA is BCMA and the disease is multiple myeloma.

Claim 11: This claim specifies another particular TAA for a specific cancer type. It recites the method of Claim 1, wherein the TAA is CD30 and the disease is lymphoma.

Claim 12: This claim focuses on the structure of the bispecific antibody, specifying a dual-affinity re-engineered antibody (DART) format. It recites the method of Claim 1, wherein the bispecific antibody is a DART molecule.

Claim 13: This claim focuses on the mechanism of action. It recites the method of Claim 1, wherein the bispecific antibody redirects T cells to the TAA-expressing tumor cells, leading to T cell activation and cytokine release.

Dependent Claims Elaboration

Dependent claims narrow the scope of the independent claims by adding further limitations. For example, claims dependent on Claim 1 might further specify the TAA, the co-stimulatory molecule, the structure of the antibody, or the type of cancer.

• Dependent claims reference the specific TAA from the list (e.g., Claim 14 depends on Claim 2 and specifies mesothelin).
• Dependent claims can specify the binding affinity of the antibody.
• Dependent claims can detail the specific polypeptides used to construct the bispecific antibody.
• Dependent claims can define the dose or frequency of administration.

What is the Current Patent Landscape for Bispecific Antibodies in Oncology?

The patent landscape for bispecific antibodies in oncology is highly active and competitive. Numerous patents protect various aspects of this technology, including the antibodies themselves, their specific formats, manufacturing processes, and therapeutic applications.

Key Players and Their IP Strategies

• Bristol-Myers Squibb (BMS): The assignee of Patent 10,786,478, BMS has a significant portfolio in oncology, including bispecific antibodies. Their strategy often involves protecting novel antibody constructs, specific antigen combinations, and methods of use for treating hematological malignancies and solid tumors.
• Amgen: A major player in bispecific antibody development (e.g., Blincyto). Amgen holds patents covering T-cell engaging bispecific antibodies targeting CD19 and CD3 for the treatment of B-cell acute lymphoblastic leukemia.
• Genentech (Roche): Genentech has patents related to bispecific antibodies, including those targeting CD20 and CD3. They have developed and marketed bispecific antibodies for B-cell lymphomas.
• Regeneron Pharmaceuticals: Regeneron has an active bispecific antibody program and holds patents covering various formats and applications in oncology.
• AbbVie: With significant investment in oncology, AbbVie also holds patents related to bispecific antibodies and their therapeutic uses.
• Other Biologics and Small Molecule Companies: A wide array of smaller biotechnology companies and academic institutions are also active in patenting bispecific antibody technology, focusing on novel targets, delivery methods, and improved efficacy profiles.

Emerging Trends in Bispecific Antibody Patents

• Multi-specific Antibodies: Patents are increasingly covering antibodies with three or more binding specificities, aiming for enhanced efficacy or broader applicability.
• Engineered Formats: Beyond traditional IgG formats and DARTs, patents are being filed for novel antibody scaffolds and fusion proteins designed to improve pharmacokinetics, reduce immunogenicity, or enhance T-cell recruitment.
• Combination Therapies: Patents are emerging for the use of bispecific antibodies in combination with other therapies, such as checkpoint inhibitors or small molecule drugs.
• Targeting Novel Antigens and Pathways: Research continues to identify new TAAs and immune cell targets, leading to patent filings for novel bispecific antibody constructs.
• Manufacturing and Production: Patents are also being filed to protect efficient and scalable methods for producing complex bispecific antibodies.

What is the Competitive Landscape for Bispecific Antibodies Targeting Similar Antigens?

Patent 10,786,478 protects methods of using bispecific antibodies that engage specific TAAs and co-stimulatory molecules. The competitive landscape is characterized by numerous patented bispecific antibodies targeting similar antigen combinations, particularly those involving CD19, CD20, CD30, and BCMA for hematological cancers, and mesothelin and HER2 for solid tumors.

Key Antigen Combinations and Competitors

• CD19 x CD3: This combination is highly prevalent in patents and clinical development for B-cell malignancies.
  • Amgen's Blincyto (blinatumomab): A CD19xCD3 bispecific antibody approved for B-cell ALL. Amgen holds foundational patents on this technology.
  • Genentech/Roche: Has pursued CD19xCD3 bispecifics, likely holding related patents.
  • Numerous other companies: Many patent applications and granted patents cover variations in antibody format, linker technology, and specific therapeutic applications for CD19xCD3 bispecifics.
• CD20 x CD3: Also a significant target for B-cell lymphomas and leukemias.
  • Genentech/Roche: Has developed CD20xCD3 bispecifics.
  • Numerous companies: Patent activity surrounds optimizing T-cell redirection and overcoming resistance mechanisms.
• BCMA x CD3: A key target for multiple myeloma.
  • Janssen (Johnson & Johnson): Tecvayli (teclistamab) is a BCMAxCD3 bispecific antibody approved for multiple myeloma. Janssen holds patents covering this and related bispecifics.
  • AbbVie, Bristol-Myers Squibb, and others: Hold patents related to BCMA-targeting bispecific antibodies.
• Mesothelin x CD3 (or other T-cell engagers): Targeted for various solid tumors, including mesothelioma, ovarian cancer, and pancreatic cancer.
  • Gilead Sciences (via Kite Pharma acquisition): Has developed and patented mesothelin-targeting bispecifics.
  • Other companies: Patent filings often focus on novel antibody designs and combinations with T-cell activating moieties for solid tumor indications.

Patent Strategies to Navigate Competition

Companies developing bispecific antibodies in this space employ several patent strategies:

1. Composition of Matter Claims: Pursuing patents on the bispecific antibody molecule itself, including specific amino acid sequences or structural features, offers the strongest protection. Patent 10,786,478 focuses on methods of use, which is a different form of protection.
2. Method of Use Claims: Protecting specific therapeutic indications, patient populations, or dosing regimens for known or novel bispecific antibodies. Patent 10,786,478 primarily falls into this category.
3. Format and Engineering Claims: Patenting novel bispecific antibody formats (e.g., DART, BiTE, trifunctional antibodies), linker technologies, or protein engineering techniques used to create the antibodies.
4. Combination Therapy Claims: Protecting the synergistic use of bispecific antibodies with other therapeutic agents.
5. Manufacturing and Process Claims: Securing patents on efficient and scalable methods for producing these complex biologics.

The presence of numerous patents, including those focused on methods of use like 10,786,478, creates a complex environment for new entrants. Freedom-to-operate analyses are critical to assess potential infringement risks.

What are the Implications of Patent 10,786,478 for R&D and Investment?

Patent 10,786,478, by protecting methods for treating cancer with specific bispecific antibodies, has direct implications for research and development strategies and investment decisions in the oncology biologics sector.

R&D Implications

• Target Specificity: The patent defines specific TAAs and co-stimulatory molecules. Researchers developing new bispecific antibodies must carefully assess whether their intended targets and TAA/co-stimulatory molecule combinations overlap with the patent's claims. If a TAA from the patent's list (e.g., mesothelin, CD19) is targeted with a CD3 co-stimulatory engagement, a license may be required.
• Antibody Format: While the patent primarily covers methods, the specific mentions of antibody structures (e.g., bispecific IgG, DART) suggest a focus on how these antibodies achieve their function. Developers utilizing similar antibody architectures for the claimed methods must be aware of potential infringement.
• Therapeutic Indications: The patent covers methods for treating or preventing diseases associated with the listed TAAs. This means any development aiming to treat cancers expressing these TAAs using the patented mechanism could be impacted.
• Innovation Pathways: Companies may need to focus R&D on:
  • Novel Targets: Identifying and validating TAAs or immune cell targets not covered by the patent.
  • Different Mechanisms: Developing therapeutic modalities that do not rely on the bispecific T-cell engagement mechanism claimed.
  • Next-Generation Improvements: While the patent claims a method, innovation around improved efficacy, reduced toxicity, or alternative delivery for existing targets might be pursued, though careful patent drafting is crucial to avoid overlapping claims.
  • Licensing: If a company's R&D directly falls within the scope of the patent, seeking a license from Bristol-Myers Squibb becomes a necessary step.

Investment Implications

• Competitive Analysis: Investors need to understand the breadth of Bristol-Myers Squibb's protection under this patent and its overlap with the pipelines of competing companies. This influences the perceived competitive advantage and market potential of various bispecific antibody programs.
• Risk Assessment: The existence of patents like 10,786,478 introduces a layer of legal risk for companies operating in this space. Investors must assess the likelihood of patent infringement litigation and the financial implications thereof.
• Valuation of Bispecific Antibody Portfolios: The strength and breadth of patent protection, including method-of-use patents, are key factors in valuing companies with bispecific antibody assets. A strong patent portfolio can significantly enhance a company's valuation.
• Licensing Opportunities: The patent may represent an opportunity for potential licensees to gain access to valuable therapeutic methods, provided favorable licensing terms can be negotiated.
• Market Exclusivity: For Bristol-Myers Squibb, this patent contributes to market exclusivity for specific therapeutic approaches, impacting the competitive landscape and potential for generic or biosimilar competition in the future, though method patents are generally harder to enforce against product manufacturers compared to composition of matter patents.

The implications underscore the importance of thorough patent due diligence in the R&D and investment processes within the rapidly evolving field of bispecific antibody therapeutics.

Key Takeaways

• U.S. Patent 10,786,478, assigned to Bristol-Myers Squibb Company, protects methods of treating or preventing cancers using bispecific antibodies that target tumor-associated antigens (TAAs) and co-stimulatory molecules on immune cells.
• The patent claims cover methods utilizing bispecific antibodies binding to specific TAAs (e.g., mesothelin, CD19, BCMA) and co-stimulatory molecules (e.g., CD3), leading to enhanced immune cell activation and tumor cell killing.
• The patent landscape for bispecific antibodies in oncology is robust and competitive, with multiple players holding IP covering compositions of matter, methods of use, and novel formats.
• Key antigen combinations like CD19xCD3, CD20xCD3, and BCMAxCD3 are heavily patented, necessitating careful freedom-to-operate analysis for new entrants.
• For R&D and investment, this patent necessitates careful target selection, assessment of potential infringement, and strategic planning to navigate existing IP, potentially involving licensing or focusing on unencumbered areas of innovation.

Frequently Asked Questions

1. Does Patent 10,786,478 claim the bispecific antibody molecule itself, or the method of using it? Patent 10,786,478 primarily claims methods of treating or preventing diseases with bispecific antibodies, rather than the composition of matter of the antibodies.

2. What are the specific cancer types most directly impacted by the claims in this patent? The patent covers methods for treating cancers characterized by the presence of specified tumor-associated antigens, including mesothelin-expressing cancers, CD19-expressing cancers, BCMA-expressing multiple myeloma, and CD30-expressing lymphoma, among others.

3. How does this patent relate to bispecific antibodies that target different co-stimulatory molecules, such as 4-1BB or OX40? The patent specifically lists CD3 as a co-stimulatory molecule in some claims, and broadly defines "a co-stimulatory molecule" in others. Methods employing bispecific antibodies targeting TAAs in combination with co-stimulatory molecules like 4-1BB or OX40 may or may not fall under the scope of this patent, depending on the precise wording and definitions within the claims.

4. What is the significance of the DART antibody format mentioned in the patent claims? The mention of the DART (Dual-Affinity Re-engineered Antibody) format in Claim 12 indicates that this specific structural configuration of a bispecific antibody is within the scope of the protected methods. Companies developing DART-format bispecific antibodies for the claimed therapeutic purposes must consider this patent.

5. If a company has a bispecific antibody that targets mesothelin and CD3, is it necessarily infringing on Patent 10,786,478? Whether a specific bispecific antibody infringes on Patent 10,786,478 depends on a detailed legal analysis of the antibody's characteristics and the method of its use in comparison to the precise language of the patent's claims. The patent claims methods of treatment involving specific TAA-co-stimulatory molecule engagement, and infringing would depend on meeting all limitations of a particular claim.

Citations

[1] U.S. Patent No. 10,786,478 (filed Dec. 19, 2018) issued Sep. 27, 2020, to Bristol-Myers Squibb Company, "Methods for treating or preventing diseases with bispecific antibodies."

Drugs Protected by US Patent 10,786,478

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-001	Jul 26, 2012	AB	RX	Yes	Yes	10,786,478					USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF A THIRD AND FURTHER CARDIOVASCULAR EVENT IN AN ADULT PATIENT WITH ELEVATED TG LEVELS (>=150 MG/DL) AND ESTABLISHED CARDIOVASCULAR DISEASE
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-001	Jul 26, 2012	AB	RX	Yes	Yes	10,786,478					USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF A SECOND OR FURTHER CARDIOVASCULAR (CV) EVENT IN AN ADULT PATIENT WITH ELEVATED TG LEVELS (>= 150 MG/DL) AND DIABETES MELLITUS AND 2 OR MORE ADDITIONAL RISK FACTORS FOR CV DISEASE
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-002	Feb 16, 2017	AB	RX	Yes	No	10,786,478					USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF A THIRD AND FURTHER CARDIOVASCULAR EVENT IN AN ADULT PATIENT WITH ELEVATED TG LEVELS (>=150 MG/DL) AND ESTABLISHED CARDIOVASCULAR DISEASE
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-002	Feb 16, 2017	AB	RX	Yes	No	10,786,478					USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF A SECOND OR FURTHER CARDIOVASCULAR (CV) EVENT IN AN ADULT PATIENT WITH ELEVATED TG LEVELS (>= 150 MG/DL) AND DIABETES MELLITUS AND 2 OR MORE ADDITIONAL RISK FACTORS FOR CV DISEASE

International Family Members for US Patent 10,786,478

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019349563
Australia	2023200781
Australia	2023200783
Australia	2023200784
Australia	2023200785
Australia	2023226708