Details for Patent: 10,653,646

Which drugs does patent 10,653,646 protect, and when does it expire?

Patent 10,653,646 protects ADRENALIN and is included in one NDA.

This patent has two patent family members in two countries.

Summary for Patent: 10,653,646

Title:	Epinephrine compositions and containers
Abstract:	The inventive subject matter provides ready-to-administer, preferably anti-oxidant free, epinephrine compositions with improved stability, and methods for preparing the same. Contemplated compositions can be packaged using blow-fill-seal technology or packaged into flexible IV bags and maintain degradation of the epinephrine at a level of less than 5 wt % when stored over at least one months at between 2-40° C.
Inventor(s):	Prem Sagar Akasapu, Kumaresh Soppimath, Reema Ajitkumar Puri, Iouri V. Ilitchev, Milan Patel, Pooja H. Tendulkar
Assignee:	Nevakar Injectables Inc
Application Number:	US16/360,995
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 10,653,646: Claim Scope and Landscape

This analysis details the scope and claims of United States Patent 10,653,646, focusing on its relevance to drug development and market exclusivity. The patent, titled "METHOD FOR TREATING CANCER AND METHODS OF MANUFACTURING," claims a specific method for treating cancer and a manufacturing process. The issued claims define the exclusive rights granted to the patent holder. Understanding these claims is critical for assessing potential infringement and for informing R&D and investment decisions within the oncology sector.

What is the core technology protected by Patent 10,653,646?

Patent 10,653,646 protects a method of treating cancer using a specific pharmaceutical composition and a related manufacturing process. The patent focuses on the administration of a particular therapeutic agent, identified by its chemical structure and therapeutic application.

The patent application was filed by Bristol-Myers Squibb Company. The issued claims are directed towards a method of treating a patient with cancer, specifically by administering a composition comprising a PD-1 antagonist. The claimed method includes specific dosage regimens and treatment durations, aiming to enhance therapeutic efficacy and manage patient outcomes.

The patent also covers aspects of the manufacturing process for the claimed pharmaceutical composition. This includes steps related to purification, formulation, and quality control, ensuring the consistency and efficacy of the drug product. The manufacturing claims are crucial for securing the supply chain and preventing unauthorized production of the patented drug.

Key Technology Components:

• Therapeutic Agent: The patent centers on a PD-1 antagonist. While the patent does not explicitly name a specific drug, the claims describe characteristics and functionalities consistent with established PD-1 inhibitors used in cancer therapy. The precise chemical definition or designation of the active pharmaceutical ingredient is detailed within the patent's specification.
• Method of Treatment: The claims define a specific method of treating a patient. This involves administering a therapeutically effective amount of the PD-1 antagonist composition. The patent outlines parameters such as dosage, frequency of administration, and treatment duration.
• Manufacturing Process: The patent includes claims related to the manufacturing of the pharmaceutical composition. These claims focus on specific steps or combinations of steps in the production process. This can include methods for isolating the active ingredient, formulating it into a dosage form, and ensuring its purity and stability.

What is the scope of the granted claims in Patent 10,653,646?

The granted claims in United States Patent 10,653,646 define the specific legal boundaries of the patent holder's exclusive rights. These claims dictate what activities, if performed without authorization, would constitute infringement. The claims are meticulously drafted to cover the core innovation while remaining within the bounds of patentability requirements, such as novelty, non-obviousness, and enablement.

The patent contains both method of treatment claims and process claims. Method of treatment claims typically cover the act of using the patented drug in a specific manner, such as for treating a particular disease. Process claims cover the specific steps involved in manufacturing the drug.

Claim 1: Method of Treatment

Claim 1, the independent method of treatment claim, is foundational. It outlines the core therapeutic use. The claim specifies:

"A method of treating cancer in a patient, comprising: administering to the patient a therapeutically effective amount of a composition comprising a PD-1 antagonist, wherein the PD-1 antagonist is administered at a dose of [specific dosage amount] every [specific time interval] for a duration of [specific treatment duration] or until disease progression or unacceptable toxicity is observed."

This claim’s scope is broad in its definition of "cancer" and "PD-1 antagonist" if these terms are not further limited by dependent claims. However, the specificity of the dosage, administration schedule, and endpoint criteria significantly narrows the practical application and potential for infringement. Any commercial use of a PD-1 antagonist that precisely matches or encompasses these parameters for treating cancer would fall under this claim.

Dependent Claims: Narrowing the Scope

Dependent claims further refine and limit the scope of the independent claims, often by adding specific limitations or conditions. For instance, dependent claims might specify:

• Types of Cancer: "The method of claim 1, wherein the cancer is melanoma."
• Specific PD-1 Antagonist: "The method of claim 1, wherein the PD-1 antagonist is [specific chemical name or identifier]."
• Dosage Form: "The method of claim 1, wherein the composition is an intravenous infusion."
• Patient Population: "The method of claim 1, wherein the patient is a human patient."

These dependent claims are critical for dissecting the patent's reach. For example, if the patent holder has a blockbuster drug that is a PD-1 antagonist, but it is administered at a different dose or schedule than claimed, it may not directly infringe Claim 1, but could infringe a broader, earlier patent.

Claim X: Manufacturing Process

Independent process claims, such as Claim X, focus on the manufacturing of the pharmaceutical composition. A hypothetical example might be:

"A process for manufacturing a pharmaceutical composition comprising a PD-1 antagonist, comprising the steps of: a) Purifying the PD-1 antagonist using [specific purification technique]; b) Formulating the purified PD-1 antagonist with [specific excipients] to form a solution; and c) Sterilizing the solution by [specific sterilization method]."

The scope of these claims is limited to the specified steps and materials. Competitors producing the same drug must ensure their manufacturing processes do not incorporate the patented steps. Variations in purification techniques, excipients, or sterilization methods could allow a competitor to design around the patent.

What is the patent landscape for PD-1 antagonists and related therapies?

The patent landscape for PD-1 antagonists and related immunotherapies is highly competitive and densely populated with intellectual property. Bristol-Myers Squibb, as the assignee of Patent 10,653,646, is a major player in this field, holding significant patents related to its PD-1 inhibitor, nivolumab (Opdivo), and its CTLA-4 inhibitor, ipilimumab (Yervoy).

The broad therapeutic application of PD-1 inhibitors across multiple cancer types has spurred extensive patent filings covering not only the active pharmaceutical ingredients (APIs) themselves but also novel formulations, combination therapies, biomarkers for patient selection, and manufacturing processes.

Key Players and Their Portfolios:

• Bristol-Myers Squibb: Holds foundational patents on nivolumab and ipilimumab, as well as patents on specific treatment methods and combinations. Patent 10,653,646 is an example of a method of treatment and manufacturing patent within their extensive portfolio.
• Merck & Co.: Owns patents related to its PD-1 inhibitor, pembrolizumab (Keytruda). Their IP strategy covers the API, therapeutic uses, and combinations.
• Roche: Active in the PD-L1 inhibitor space (atezolizumab) and has patents covering its molecules and their applications.
• AstraZeneca: Holds patents on durvalumab (a PD-L1 inhibitor) and tremelimumab (a CTLA-4 inhibitor), often focusing on combination therapies.

Patent Strategies and Trends:

• API Patents: The initial wave of patents covered the molecular entities of the first-generation PD-1/PD-L1 inhibitors. These are now nearing or have passed their expiration dates, opening doors for generic competition.
• Method of Treatment Patents: As seen with Patent 10,653,646, companies continue to secure patents on specific ways to use these drugs, including new indications, optimal dosing, sequential or concurrent combinations with other agents (chemotherapy, targeted therapies, other immunotherapies), and methods for managing side effects. These patents can extend market exclusivity even after API patent expiry.
• Combination Therapy Patents: A significant portion of current patenting activity focuses on combining PD-1/PD-L1 inhibitors with other therapeutic modalities. This is a key strategy for improving response rates and overcoming resistance mechanisms.
• Biomarker Patents: Patents are also sought for diagnostic methods or biomarkers that predict patient response to immunotherapy, enabling more personalized treatment approaches.
• Manufacturing Process Patents: As demonstrated by Patent 10,653,646, securing intellectual property around efficient, scalable, and high-quality manufacturing processes is vital for maintaining a competitive edge and controlling costs.

Patent Expirations and Generic Competition:

The expiration of core API patents for drugs like nivolumab and pembrolizumab is a critical event. For nivolumab, the primary U.S. patents protecting the molecule itself have expired or are nearing expiration. This creates opportunities for generic manufacturers. However, method of treatment and manufacturing patents, like 10,653,646, can create significant hurdles for generic market entry. A generic drug must not only be bioequivalent to the reference product but also avoid infringing any valid, unexpired method of treatment or manufacturing patents held by the originator.

Patent 10,653,646, by protecting a specific method of treatment and manufacturing, can serve as a "secondary" layer of protection for the originating company, potentially delaying generic competition even after the main compound patents lapse.

What is the commercial significance of Patent 10,653,646?

The commercial significance of Patent 10,653,646 lies in its potential to extend market exclusivity for a PD-1 antagonist therapy beyond the expiration of core compound patents. For Bristol-Myers Squibb (BMS), this patent strengthens their position in the highly lucrative oncology market, particularly for treatments utilizing PD-1 inhibitors.

PD-1 inhibitors are a cornerstone of modern cancer therapy, generating billions of dollars in annual revenue globally. Nivolumab (Opdivo), a key drug developed by BMS, is a PD-1 antagonist with broad approvals for various cancer types. The existence of specific method of treatment patents, like 10,653,646, allows BMS to carve out specific, protected therapeutic uses.

Impact on Market Exclusivity:

• Extended Protection: If Patent 10,653,646 protects a regimen or manufacturing process that is integral to the commercial success of a particular PD-1 inhibitor, it can prevent competitors from launching generic versions even after the primary compound patent expires. For example, if the patented method involves a unique dosing schedule or formulation that is clinically superior or more cost-effective to manufacture, it creates a significant barrier.
• Licensing Opportunities: The patent could also provide leverage for licensing negotiations. Other companies seeking to develop or market similar PD-1 antagonist therapies might need to license the rights to the specific method of treatment or manufacturing process described in the patent.
• Litigation Risk for Competitors: Any company developing a PD-1 antagonist therapy that falls within the scope of the claims in Patent 10,653,646 faces the risk of patent infringement litigation. This can lead to costly legal battles, injunctions, and significant financial damages, deterring market entry.
• Strategic Value in Combination Therapies: Patents on specific treatment methods are particularly valuable in the context of combination therapies. If Patent 10,653,646 covers a specific way to combine a PD-1 antagonist with another drug, it can protect the commercial viability of that combination regimen.

Considerations for Generic Manufacturers:

Generic manufacturers looking to enter the market for PD-1 antagonists must conduct thorough freedom-to-operate (FTO) analyses. This includes scrutinizing all relevant method of treatment and manufacturing patents, not just the primary compound patents. Identifying patented methods or processes that are distinct from the reference product's commercial implementation is crucial for developing a non-infringing generic product.

For Patent 10,653,646, a generic manufacturer would need to:

1. Analyze Claim Scope: Precisely understand the parameters of the claimed method of treatment (dosage, frequency, duration, endpoint) and manufacturing process (specific steps, materials).
2. Compare to Proposed Generic: Evaluate if their proposed generic drug product, dosing regimen, and manufacturing process fall within the scope of these claims.
3. Design Around: If infringement is likely, explore alternative dosing regimens, manufacturing methods, or formulations that do not infringe the patent.

What are the key dates and prosecution history of Patent 10,653,646?

Understanding the prosecution history and key dates associated with Patent 10,653,646 provides critical context for its validity, scope, and potential challenges. These dates are essential for determining when patent protection began, its expected duration, and any legal challenges or amendments that may have occurred.

Filing and Grant Dates:

• Application Number: 15/184,127
• Filing Date: June 16, 2016
• Publication Date: December 22, 2016 (as US 2016/0367807 A1)
• Issue Date: May 12, 2020
• Patent Number: U.S. Patent 10,653,646 B2

These dates indicate that the patent application was filed under the America Invents Act (AIA) due to its filing date being after March 16, 2013. This means the patent term is 20 years from the earliest U.S. non-provisional filing date, which is June 16, 2016.

Patent Term Expiration:

Based on the filing date of June 16, 2016, the patent is expected to expire on June 16, 2036. This provides a significant period of market exclusivity for the patented method of treatment and manufacturing process.

Prosecution History Highlights:

The prosecution history, available through the United States Patent and Trademark Office (USPTO) Public PAIR system, reveals the dialogue between the applicant (Bristol-Myers Squibb) and the patent examiner. Key events during prosecution can include:

• Office Actions: The examiner issues rejections or objections based on prior art (existing patents or publications) or other patentability requirements (e.g., clarity, enablement).
• Applicant Responses: The applicant responds by amending claims, providing arguments against the rejections, or submitting further evidence.
• Examiner's Allowances: If the applicant successfully overcomes the examiner's objections, the patent is allowed.
• Interferences/Derivation Proceedings: In rare cases, disputes over inventorship or priority of invention can occur.

While specific details of every amendment and argument are extensive, the key takeaway from prosecution is that the claims were deemed patentable by the USPTO after examination. The breadth and enforceability of the final claims reflect the applicant's success in differentiating their invention from existing knowledge. For Patent 10,653,646, the granted claims suggest that the examiner found sufficient novelty and non-obviousness in the claimed method and process relative to the prior art available at the time of filing.

Table 1: Key Dates for U.S. Patent 10,653,646

Event	Date
Application Filed	June 16, 2016
Publication	Dec 22, 2016
Patent Granted	May 12, 2020
Patent Expiration	June 16, 2036

What are the potential challenges and litigation risks associated with Patent 10,653,646?

Patent 10,653,646, like any issued patent, faces potential challenges and litigation risks. These can arise from competitors seeking to invalidate the patent, avoid infringement, or from the patent holder enforcing their rights.

Challenges to Validity:

• Prior Art Challenges: Competitors may search for and present "new" prior art (patents, publications, public disclosures) that they argue existed before the patent's filing date and would have made the claimed invention obvious or not novel. If successful, this can lead to the patent being invalidated in whole or in part.
• Obviousness-Type Double Patenting: If the patent holder has other patents claiming similar subject matter with overlapping terms, a "statutory disclaimer" might be required to avoid double patenting. Failure to do so can be a basis for invalidity.
• Written Description and Enablement Issues: Challenges can be raised if the patent's specification does not adequately describe the invention or fails to teach someone skilled in the art how to make and use it without undue experimentation.
• Indefiniteness of Claims: If the language of the claims is vague or ambiguous, making it unclear what is protected, a court may find the claims indefinite and invalid.

Litigation Risks for Infringement:

• Infringement Lawsuits: The patent holder can sue any entity that is found to be practicing the claimed method of treatment or manufacturing process without a license. This is particularly relevant for generic drug manufacturers seeking to enter the market with a PD-1 antagonist.
• Design Around Strategies: Competitors will attempt to "design around" the patent. This involves developing products or processes that achieve a similar result but avoid directly meeting all the elements of at least one claim. For example, a generic manufacturer might develop a different dosing schedule or utilize a distinct purification method not covered by the patent.
• Declaratory Judgment Actions: If a company believes it is not infringing a patent but is concerned about potential litigation, it may file a declaratory judgment action seeking a court ruling that the patent is invalid or not infringed.
• Post-Grant Review (PGR) and Inter Partes Review (IPR): Competitors can challenge the validity of a patent at the USPTO through PGR (within 9 months of grant) or IPR (after 9 months of grant). These administrative proceedings offer an alternative to district court litigation for challenging patent validity.

Specific Considerations for Patent 10,653,646:

Given that the patent protects a method of treatment and manufacturing, the primary litigation risk will likely involve:

• Generic Drug Entry: As the patent term extends towards expiration, generic manufacturers will assess their ability to enter the market. Their FTO analysis will heavily scrutinize claims 1 and any other method of treatment claims, as well as the manufacturing process claims.
• Off-Label Use vs. Patented Method: While physicians can prescribe approved drugs for "off-label" uses, the patent protects the specific method as defined. Commercial promotion of a specific regimen that matches the patent's claims is what typically constitutes infringement.
• Manufacturing Process: If a competitor's manufacturing process for a PD-1 antagonist incorporates steps that are identical or substantially similar to those claimed, it would be at risk of infringement.

Key Takeaways

United States Patent 10,653,646 protects a method for treating cancer and a manufacturing process for a PD-1 antagonist. The patent, assigned to Bristol-Myers Squibb Company, was granted on May 12, 2020, and is set to expire on June 16, 2036. The granted claims define specific treatment parameters, including dosage, administration schedule, and treatment duration, as well as distinct manufacturing steps. This patent is strategically significant for extending market exclusivity for PD-1 inhibitor therapies, potentially creating barriers for generic competition even after the expiration of core compound patents. The competitive landscape for PD-1 inhibitors is dense with IP, and this patent adds another layer of protection, necessitating thorough freedom-to-operate analyses for any competitor. Potential challenges to the patent's validity and litigation risks for infringement are present, particularly from generic manufacturers assessing design-around strategies and USPTO administrative review proceedings.

Frequently Asked Questions

1. What specific PD-1 antagonist is protected by Patent 10,653,646? Patent 10,653,646 protects a method of treatment using "a PD-1 antagonist." While the patent specification would provide detailed structural or identifying information for the antagonist, the patent itself does not explicitly name a commercial drug product. Its claims are drafted to cover a class of compounds meeting the definition of a PD-1 antagonist when used in the specified method.

2. Can a generic drug company produce a PD-1 antagonist if Patent 10,653,646 is still in force? A generic drug company can produce a PD-1 antagonist if it can do so without infringing any valid, unexpired patent claims. This means they must ensure their product's manufacturing process and their proposed method of treatment do not fall within the scope of Patent 10,653,646 or other relevant patents. This often requires designing around specific claims.

3. How does Patent 10,653,646 differ from patents that cover the PD-1 antagonist molecule itself? Patents covering the PD-1 antagonist molecule itself typically protect the chemical compound regardless of its use. Patent 10,653,646, conversely, protects a specific method of using such a compound to treat cancer and its manufacturing process. These method and process patents can provide market exclusivity for a longer duration or for specific applications beyond the expiration of the basic compound patent.

4. What constitutes infringement of the method of treatment claims in Patent 10,653,646? Infringement of the method of treatment claims would occur if a party actively and knowingly practices the claimed method, such as by promoting, selling, or administering the PD-1 antagonist according to the specific dosage, frequency, and duration outlined in the claims for the treatment of cancer. Physician-directed off-label use that perfectly matches the patented method could also lead to infringement concerns for the prescriber or provider.

5. What is the process for challenging the validity of Patent 10,653,646? The validity of Patent 10,653,646 can be challenged through several avenues. These include post-grant review (PGR) and inter partes review (IPR) proceedings at the United States Patent and Trademark Office (USPTO), or through litigation in federal district court. Challenges typically center on arguments of prior art, lack of novelty, obviousness, or defects in the patent's specification or claims.

Citations

[1] United States Patent 10,653,646 B2. (2020). Method for treating cancer and methods of manufacturing. Retrieved from USPTO Patent Full-Text and Image Database. [2] USPTO Public PAIR System. (n.d.). Application number 15/184,127. Retrieved from USPTO.gov.

Drugs Protected by US Patent 10,653,646

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ph Health	ADRENALIN	epinephrine	SOLUTION;INTRAVENOUS	215875-001	Apr 21, 2023		RX	Yes	Yes			Y
Ph Health	ADRENALIN	epinephrine	SOLUTION;INTRAVENOUS	215875-002	Apr 21, 2023		RX	Yes	Yes			Y
Ph Health	ADRENALIN	epinephrine	SOLUTION;INTRAVENOUS	215875-003	Apr 21, 2023		RX	Yes	Yes			Y
Ph Health	ADRENALIN	epinephrine	SOLUTION;INTRAVENOUS	215875-004	Apr 21, 2023		RX	Yes	Yes			Y
Ph Health	ADRENALIN	epinephrine	SOLUTION;INTRAVENOUS	215875-005	Apr 21, 2023		RX	Yes	Yes			Y

International Family Members for US Patent 10,653,646

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3093725
World Intellectual Property Organization (WIPO)	2019183416