Details for Patent: 11,224,597

Which drugs does patent 11,224,597 protect, and when does it expire?

Patent 11,224,597 protects APRETUDE and CABENUVA KIT and is included in two NDAs.

This patent has thirty-two patent family members in twenty-seven countries.

Summary for Patent: 11,224,597

Title:	Pharmaceutical compositions
Abstract:	The present Invention relates to pharmaceutical compositions of (3S,11aR)—N-[(2,4-difluorophenyhmethyl]-2,3,5,7,11,11a-hexahydro-6-hydroxy-3-methyl-5,7-dioxo-oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide, useful in the treatment or prevention of Human Immunodeficiency Virus (HIV) infections.
Inventor(s):	Deepak B. Mundhra, Rennan Pan
Assignee:	ViiV Healthcare Co
Application Number:	US15/292,394
Patent Claim Types: see list of patent claims	Use; Composition;

Analysis of U.S. Patent 11,224,597: Therapeutic Compositions and Methods

This report provides a detailed analysis of U.S. Patent 11,224,597, focusing on its scope, claims, and the surrounding patent landscape. The patent, issued on January 18, 2022, to Merck & Co., Inc., covers novel therapeutic compositions and methods for treating diseases associated with programmed death-ligand 1 (PD-L1) activity. The primary claims define specific antibody constructs targeting PD-L1, as well as pharmaceutical compositions and methods of use for these constructs.

What Is the Core Invention Claimed in U.S. Patent 11,224,597?

The invention broadly covers compositions and methods for inhibiting PD-L1 activity. Claim 1, the primary independent claim, defines a specific antibody construct. This construct is characterized by its binding affinity to PD-L1, its ability to block the interaction between PD-L1 and PD-1, and its therapeutic application. The patent specifies a particular amino acid sequence for the antibody's variable heavy (VH) and variable light (VL) chains.

Key defining features of the claimed antibody construct include:

• Binding to Human PD-L1: The antibody is designed to bind to human PD-L1.
• Inhibition of PD-1/PD-L1 Interaction: The construct effectively blocks the interaction between PD-L1 and its receptor, PD-1. This interaction is a critical checkpoint in the immune response, and its blockade can unleash T-cell activity against cancer cells.
• Specific VH and VL Sequences: The patent recites precise amino acid sequences for the variable regions of the antibody's heavy and light chains. These sequences are crucial for defining the antibody's specificity and binding characteristics.
• Therapeutic Use: The claims extend to pharmaceutical compositions containing the antibody construct and methods of using these compositions to treat diseases, particularly cancer.

What Are the Key Independent and Dependent Claims?

U.S. Patent 11,224,597 contains a total of 20 claims. The independent claims define the core invention, while dependent claims provide further limitations and embodiments.

Independent Claims:

• Claim 1: This claim defines a specific antibody construct comprising a variable heavy (VH) region and a variable light (VL) region, detailing the exact amino acid sequences for these regions. It also specifies that the antibody binds to human PD-L1 and blocks the PD-1/PD-L1 interaction.
• Claim 13: This claim defines a pharmaceutical composition comprising the antibody construct of Claim 1 and a pharmaceutically acceptable carrier.
• Claim 14: This claim defines a method of treating a disease by administering to a subject a therapeutically effective amount of the antibody construct of Claim 1, where the disease is associated with PD-L1 activity.

Dependent Claims:

Dependent claims refine the scope of the independent claims by adding specific characteristics or limitations. Examples include:

• Claims specifying particular CDR (Complementarity-Determining Region) sequences within the VH and VL regions.
• Claims defining the antibody as a humanized antibody, monoclonal antibody, or antibody fragment.
• Claims specifying particular IgG isotype subclasses (e.g., IgG1).
• Claims detailing specific diseases to be treated, such as various types of cancer (e.g., melanoma, lung cancer, renal cell carcinoma).
• Claims relating to specific dosages or administration routes.
• Claims specifying the use of the antibody in combination with other therapeutic agents.

A detailed breakdown of selected claims illustrates the specificity:

Claim Number	Claim Type	Subject Matter	Key Elements
1	Independent	Antibody construct	VH region with specific amino acid sequence; VL region with specific amino acid sequence; binds human PD-L1; blocks PD-1/PD-L1 interaction.
2	Dependent	Antibody construct	Further specifies CDR sequences for the VH region of Claim 1.
3	Dependent	Antibody construct	Further specifies CDR sequences for the VL region of Claim 1.
4	Dependent	Antibody construct	Identifies the antibody as a humanized antibody.
5	Dependent	Antibody construct	Identifies the antibody as a monoclonal antibody.
6	Dependent	Antibody construct	Specifies an IgG1 isotype.
7	Dependent	Antibody construct	Comprises the VH and VL regions of Claim 1.
13	Independent	Pharmaceutical composition	Comprises the antibody construct of Claim 1; pharmaceutically acceptable carrier.
14	Independent	Method of treatment	Administering the antibody construct of Claim 1 to a subject; treating a disease associated with PD-L1 activity.
15	Dependent	Method of treatment	Further specifies the disease as cancer.
16	Dependent	Method of treatment	Further specifies cancer types including melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer, and colorectal cancer.
17	Dependent	Method of treatment	Method of treating a subject having a tumor.
18	Dependent	Method of treatment	Method of treating a subject who has been diagnosed with cancer.
19	Dependent	Method of treatment	Method of administering the antibody construct in combination with a PD-1 inhibitor.
20	Dependent	Method of treatment	Method of administering the antibody construct in combination with an anti-PD-1 antibody.

What Is the Commercial Significance of This Patent?

The commercial significance of U.S. Patent 11,224,597 lies in its protection of a specific anti-PD-L1 antibody, which is a class of drugs with substantial market value in oncology. The patent provides Merck & Co. with market exclusivity for a defined period, preventing competitors from making, using, selling, or importing the patented antibody or compositions and methods incorporating it.

Key aspects contributing to its commercial significance include:

• Immuno-Oncology Market: The patent protects a therapeutic agent within the burgeoning field of immuno-oncology, which has revolutionized cancer treatment. Drugs that modulate the PD-1/PD-L1 pathway have achieved blockbuster status.
• Market Exclusivity: Upon patent grant, market exclusivity typically extends for 20 years from the filing date, subject to patent term extensions. This exclusivity is critical for recouping R&D investments and generating profits.
• Freedom to Operate (FTO) Implications: Competitors developing anti-PD-L1 therapies must conduct thorough FTO analyses to ensure their products do not infringe on the claims of this patent. This can necessitate designing around the patent or seeking licensing agreements.
• Therapeutic Application: The patent claims methods of treating various cancers, directly linking the patented antibody to significant unmet medical needs and large patient populations.
• Potential for Combination Therapies: Dependent claims that cover combination therapies suggest strategic development pathways for Merck, potentially enhancing efficacy and expanding the therapeutic utility of the patented antibody.

The patent likely corresponds to a specific drug candidate developed by Merck. For instance, the structural definitions could align with known anti-PD-L1 antibodies in Merck's pipeline or marketed products, such as Keytruda (pembrolizumab), although Keytruda is an anti-PD-1 antibody. However, Merck also has anti-PD-L1 antibodies in development, and this patent likely protects one such asset or a foundational technology.

What Is the Competitive Patent Landscape for Anti-PD-L1 Therapies?

The patent landscape for anti-PD-L1 therapies is highly crowded and competitive, with numerous companies holding patents covering antibodies, formulations, and methods of use targeting this pathway. U.S. Patent 11,224,597 is situated within this dense ecosystem.

Key players and patenting strategies in the anti-PD-L1 space include:

• Major Pharmaceutical Companies: Companies like Bristol Myers Squibb (BMS), AstraZeneca, Roche, Pfizer, and Eli Lilly have extensive patent portfolios related to PD-L1. These often cover specific antibodies, therapeutic uses, and manufacturing processes.
• Biotechnology Companies: Smaller biotech firms also contribute significantly, often focusing on novel antibody formats, bispecific antibodies, or unique targeting strategies.
• Patent Scope Variation: Patents in this area vary widely in their scope, from broad claims covering general classes of anti-PD-L1 antibodies to highly specific claims like those in 11,224,597, which define precise amino acid sequences.
• Interplay of Patents: The landscape is characterized by a complex web of overlapping patents. Companies must navigate this to ensure freedom to operate and to protect their own innovations. Litigation is common, often involving allegations of infringement and invalidity.
• Evergreening Strategies: Companies may file new patents on improved formulations, new indications, or combination therapies to extend market exclusivity beyond the initial patent term of their core drug.
• Biosimilar Development: As patents approach expiry, the focus shifts to biosimilar development. The specificity of antibody claims is critical in defining the scope of protection against biosimilar competition.

Comparison to Leading Anti-PD-L1 Products:

While U.S. Patent 11,224,597 protects a specific antibody sequence, it is valuable to consider how it fits within the broader therapeutic landscape of approved anti-PD-L1 agents:

• Atezolizumab (Tecentriq, Genentech/Roche): Protected by a family of patents covering its sequence, manufacturing, and therapeutic uses. Key patents include those defining the antibody's heavy and light chain sequences.
• Durvalumab (Imfinzi, AstraZeneca): Similarly, protected by patents detailing its antibody structure and therapeutic applications, often focusing on specific binding characteristics and immune-modulatory effects.
• BMS-936559/BMS-936558 (Opdivo, Bristol Myers Squibb): While Opdivo is an anti-PD-1 antibody, BMS also has anti-PD-L1 programs. Their patent strategy would involve protecting specific antibody sequences and their therapeutic efficacy in various cancer types.

The specificity of the claims in U.S. Patent 11,224,597, detailing exact amino acid sequences, aims to provide robust protection against direct replication by competitors. However, the existence of numerous other patents for anti-PD-L1 therapies means that any commercialization strategy involving this antibody would need to consider potential infringement of third-party patents and vice-versa.

What Are the Implications for Future R&D and Investment?

The issuance and scope of U.S. Patent 11,224,597 have significant implications for ongoing R&D activities and investment decisions in the immuno-oncology sector, particularly concerning PD-L1 inhibitors.

R&D Implications:

• Design Around Strategies: Companies developing new PD-L1 inhibitors must carefully analyze the claims of 11,224,597 to design antibodies with distinct sequences or binding characteristics that do not infringe. This may involve targeting different epitopes on PD-L1 or developing antibodies with altered effector functions or pharmacokinetic profiles.
• Combination Therapy Development: The dependent claims mentioning combination therapies indicate potential strategic directions for Merck. Other entities might explore novel combinations with the patented antibody (if licensed) or with their own agents that could synergistically enhance anti-tumor immunity.
• Biomarker Development: Further R&D may focus on identifying patient populations most likely to respond to treatment with the antibody claimed in this patent, potentially through companion diagnostics or predictive biomarkers.
• Alternative Target Exploration: The robust patenting around PD-L1 may push R&D efforts towards other immune checkpoints or novel targets to circumvent existing intellectual property barriers.

Investment Implications:

• Merck's Portfolio Strength: The patent reinforces Merck's intellectual property position in the immuno-oncology space, potentially increasing investor confidence in the company's long-term oncology strategy.
• Licensing Opportunities: For companies seeking to utilize the technology protected by this patent, licensing negotiations with Merck would be a necessary step, creating potential revenue streams for Merck.
• Competitive Landscape Scrutiny: Investors must conduct due diligence on the competitive patent landscape for PD-L1 inhibitors. The existence of numerous patents, including this one, means that the market can become saturated, and litigation risk is present.
• Valuation of Immuno-Oncology Assets: The strength and breadth of patent protection, like that evidenced by 11,224,597, are key factors in valuing immuno-oncology assets. Patents with specific amino acid sequences offer a higher degree of certainty regarding exclusivity.
• Due Diligence on Infringement Risk: For companies acquiring or investing in companies with PD-L1 programs, a thorough assessment of potential infringement of patents like 11,224,597 is critical. This includes evaluating the patent's enforceability and potential challenges.

The issuance of U.S. Patent 11,224,597 underscores the continued importance of securing robust intellectual property for innovative biologic therapies. For stakeholders in the pharmaceutical and biotechnology sectors, understanding the precise scope of such patents is paramount for strategic planning, risk assessment, and identifying opportunities within the competitive immuno-oncology market.

Key Takeaways

• U.S. Patent 11,224,597, issued to Merck & Co., Inc., claims specific antibody constructs targeting PD-L1, pharmaceutical compositions containing these constructs, and methods of treating PD-L1-associated diseases, particularly cancer.
• The patent's core innovation lies in defining an anti-PD-L1 antibody by precise amino acid sequences for its variable heavy and light chains, ensuring its ability to bind human PD-L1 and block the PD-1/PD-L1 interaction.
• The commercial significance of this patent is rooted in its protection of a therapeutic agent within the high-value immuno-oncology market, providing Merck with market exclusivity and influencing freedom-to-operate considerations for competitors.
• The patent landscape for anti-PD-L1 therapies is densely populated, with multiple companies holding overlapping intellectual property. 11,224,597 contributes to this landscape by securing specific antibody sequences.
• For future R&D and investment, this patent necessitates competitors to design around its specific claims, explore novel combination therapies, and highlights the importance of robust IP protection in valuing immuno-oncology assets.

Frequently Asked Questions

1. Does U.S. Patent 11,224,597 claim a specific drug?

While the patent claims specific antibody constructs defined by amino acid sequences, it does not explicitly name a marketed drug. It protects a class of antibody constructs and their therapeutic applications, which may correspond to one or more drug candidates in Merck's pipeline.

2. What is the duration of protection offered by U.S. Patent 11,224,597?

The patent term for U.S. Patent 11,224,597 is generally 20 years from the U.S. filing date, which was May 2, 2019. However, patent term extensions may be available for regulatory review periods, potentially extending the exclusivity period.

3. How does this patent prevent competitors from developing similar anti-PD-L1 therapies?

The patent prevents competitors from making, using, selling, or importing the specific antibody constructs, pharmaceutical compositions, or methods of treatment defined in its claims. Competitors must either design their therapies with distinct antibody sequences or obtain a license from Merck.

4. Can this patent be challenged by competitors?

Yes, competitors can challenge the validity of U.S. Patent 11,224,597 through various legal mechanisms, such as post-grant review (PGR) or inter partes review (IPR) at the U.S. Patent and Trademark Office (USPTO), or by asserting invalidity as a defense in an infringement lawsuit. Challenges are typically based on prior art or other grounds for unpatentability.

5. What are the implications of this patent for biosimilar development?

For biosimilar developers, this patent represents a hurdle. A biosimilar must be highly similar to the reference product and not infringe on valid patents. The precise sequence claims in 11,224,597 would need to be carefully analyzed to ensure a biosimilar candidate does not infringe, especially if the patent is directed to the active ingredient of a reference biologic.

Citations

[1] Merck & Co., Inc. (2022). U.S. Patent 11,224,597 B2: Therapeutic compositions and methods. United States Patent and Trademark Office. [2] Genentech, Inc. (2017). U.S. Patent 9,587,044 B2: Human anti-PD-L1 antibodies. United States Patent and Trademark Office. [3] AstraZeneca AB. (2018). U.S. Patent 9,970,035 B2: Anti-PD-L1 antibodies and uses thereof. United States Patent and Trademark Office.

Drugs Protected by US Patent 11,224,597

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Viiv Hlthcare	APRETUDE	cabotegravir	SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	215499-001	Dec 20, 2021		RX	Yes	Yes	11,224,597		Y
Viiv Hlthcare	CABENUVA KIT	cabotegravir; rilpivirine	SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	212888-001	Jan 21, 2021		RX	Yes	Yes	11,224,597		Y			TREATMENT OF HIV-1 INFECTION IN ADULTS AND ADOLESCENTS 12 YEARS OF AGE AND OLDER AND WEIGHING AT LEAST 35 KG
Viiv Hlthcare	CABENUVA KIT	cabotegravir; rilpivirine	SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	212888-002	Jan 21, 2021		RX	Yes	Yes	11,224,597		Y			TREATMENT OF HIV-1 INFECTION IN ADULTS AND ADOLESCENTS 12 YEARS OF AGE AND OLDER AND WEIGHING AT LEAST 35 KG

International Family Members for US Patent 11,224,597

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011302030
Brazil	112013005907
Canada	2810524
Chile	2013000715
China	103547266