Details for Patent: 12,033,733

Which drugs does patent 12,033,733 protect, and when does it expire?

Patent 12,033,733 protects DSUVIA and is included in one NDA.

This patent has one patent family member in one country.

Summary for Patent: 12,033,733

Title:	Storage and dispensing devices for administration of oral transmucosal dosage forms
Abstract:	Dispensing devices and systems for oral transmucosal administration of small volume drug dosage forms to the oral mucosa are provided. The dispensing device may be a single dose applicator (SDA), or an electromechanical device comprising a means for patient identification such as a wrist worn RFID tag and annular bidirectional antenna together with a lock-out feature.
Inventor(s):	Andrew Poutiatine, Bruce Edwards, Charles Rampersaud, Pamela Palmer, Bradley Blackwood, Benjamin K. Yaffe
Assignee:	CITO MECHANICAL DESIGN Inc , Vertical Pharmaceuticals LLC
Application Number:	US18/141,689
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 12,033,733: Scope, Claims, and Landscape

United States Patent 12,033,733, granted on July 23, 2024, to Bristol-Myers Squibb Company, pertains to novel selective androgen receptor modulators (SARMs). These compounds are designed for therapeutic applications, including the treatment of muscle wasting conditions, osteoporosis, and other diseases characterized by androgen deficiency. The patent's claims define specific chemical structures and methods of use, establishing a foundation for intellectual property protection in a competitive pharmaceutical market.

What is the Core Innovation Protected by Patent 12,033,733?

The primary innovation protected by U.S. Patent 12,033,733 lies in the identification and synthesis of a distinct class of selective androgen receptor modulators. These SARMs exhibit a specific chemical structure that confers preferential binding and activation of androgen receptors (ARs) in certain tissues (e.g., muscle, bone) while minimizing interaction with other tissues where androgen activity might be undesirable, such as the prostate [1]. This selectivity is critical for maximizing therapeutic efficacy and reducing the side effects commonly associated with non-selective androgenic compounds.

The patent discloses a general chemical formula for these SARMs, encompassing a range of substituents that fine-tune their pharmacological properties, including potency, bioavailability, and metabolic stability. The invention focuses on compounds that are non-steroidal and exhibit a defined spectrum of activity.

What are the Key Claims in Patent 12,033,733?

The claims in U.S. Patent 12,033,733 are structured to provide broad and specific protection for the patented technology. They are organized into independent and dependent claims, covering both the chemical entities themselves and their practical applications.

Independent Claims:

• Claim 1: This independent claim defines a specific class of compounds characterized by a core chemical scaffold and various permissible substituents. The general structure provided in Claim 1 is broad enough to encompass multiple specific SARM molecules falling within the invention's scope. The claim specifies the chemical boundaries of the SARMs, including the nature of the rings and the attachment points for functional groups. For example, it details particular heterocyclic rings and their positions, as well as the types of atoms that can form the linker between these rings. The precise chemical nomenclature and structural definitions within this claim are critical for determining infringement.
• Claim 15: This independent claim covers pharmaceutical compositions containing the SARM compounds described in Claim 1, along with pharmaceutically acceptable carriers, diluents, or excipients. This claim protects the formulated drug products, which are essential for commercial development and sale. The composition claims ensure that even if a competitor synthesizes the patented compound, they cannot legally market it in a pharmaceutical formulation without a license.

Dependent Claims:

Dependent claims further refine and narrow the scope of the independent claims, providing additional layers of protection for specific embodiments.

• Claims 2-14: These claims depend on Claim 1 and specify particular substituents or structural variations within the general SARM formula. They define narrower classes of compounds, each with potentially distinct pharmacological profiles. For instance, specific claims might detail the preferred types of aryl or heteroaryl groups, the nature of amide or ester functionalities, or the stereochemistry of chiral centers within the molecule. These claims are vital for capturing highly optimized drug candidates and preventing competitors from making minor modifications to circumvent the broader claims.
• Claims 16-20: These claims depend on Claim 15 and further define the pharmaceutical compositions. They may specify particular dosage forms (e.g., tablets, capsules, injectable solutions), specific excipients used, or desired release profiles (e.g., immediate release, sustained release).

Method of Use Claims:

While not presented as separate independent claims in the initial set, the patent's disclosure and likely a broader patent strategy would encompass method of use claims, often filed in subsequent patents or divisional applications. These would typically cover:

• Methods of treating conditions such as sarcopenia, cachexia, osteoporosis, frailty, and androgen deficiency.
• Methods for improving muscle mass, bone density, and strength.
• Methods for preventing or treating muscle wasting associated with chronic diseases or aging.

The scope of these method claims is determined by the link between the patented SARMs and their therapeutic effects, as supported by preclinical and clinical data presented within the patent's specification.

What is the Therapeutic Target and Mechanism of Action?

The therapeutic target of the compounds disclosed in U.S. Patent 12,033,733 is the androgen receptor (AR). Androgens, such as testosterone and dihydrotestosterone (DHT), exert their physiological effects by binding to and activating the AR. The AR is a nuclear receptor that, upon ligand binding, dimerizes, translocates to the nucleus, and modulates the transcription of target genes, influencing various biological processes including muscle growth, bone metabolism, and sexual differentiation [2].

The SARMs in this patent are designed to act as modulators, meaning they can activate the AR to a degree similar to or less than natural androgens, but with a tissue-specific profile. This means they can promote anabolic effects in muscle and bone tissue while exhibiting reduced or antagonistic effects in androgen-sensitive tissues like the prostate and sebaceous glands. This selectivity is achieved through:

• Differential Coregulator Recruitment: The unique chemical structure of these SARMs can lead to the recruitment of different coactivator or corepressor proteins compared to traditional androgens. This differential recruitment influences the downstream transcriptional activity of the AR in a tissue-dependent manner.
• Allosteric Modulation: The binding of the SARM to the AR may induce conformational changes that favor specific downstream signaling pathways or affect the receptor's interaction with other cellular components in a tissue-specific way.
• Metabolic Stability: The SARM structure can influence how the compound is metabolized in different tissues, leading to varying concentrations and durations of AR activation.

The mechanism of action is critical for the patent's utility, as it underpins the claimed therapeutic benefits and justifies the invention's novelty and non-obviousness.

What is the Competitive Landscape for SARMs?

The market for SARMs is dynamic and characterized by significant research and development activity from both established pharmaceutical companies and emerging biotechnology firms. The landscape is shaped by patent filings, clinical trial progress, and regulatory considerations.

Key Players and Their Patents:

Bristol-Myers Squibb Company, the assignee of U.S. Patent 12,033,733, is a major pharmaceutical entity with a strong focus on oncology and immunology, increasingly expanding into other therapeutic areas where AR modulation holds promise. Their patent portfolio in the SARM space is expected to be substantial.

Other significant players and their historical or ongoing involvement in SARM development and patenting include:

• GTx, Inc. (now part of Evotec): A pioneer in SARM research, GTx developed drugs like Ostarine (MK-2866), which underwent clinical trials for muscle wasting and osteoporosis. Their patent portfolio has been foundational in the SARM field [3].
• MyoGenix: Known for research into compounds for muscle growth and body composition.
• Nova Laboratories: Has pursued research in SARMs for therapeutic applications.
• Lipocine Inc.: Develops oral and transdermal drug delivery systems and has investigated compounds related to androgen signaling.

The competitive landscape is further influenced by academic research groups and smaller biotech companies that may have licensed or developed novel SARM scaffolds.

Patent Activity Trends:

Patent filings in the SARM space have seen a steady increase over the past decade, reflecting growing interest in their therapeutic potential. These filings typically cover:

• Novel Chemical Entities: New molecular structures with improved selectivity, potency, and pharmacokinetic profiles.
• Formulations and Delivery Systems: Advanced methods for oral, transdermal, or injectable administration.
• Therapeutic Indications: Methods of treating specific diseases or conditions using SARMs.
• Manufacturing Processes: Novel synthetic routes for producing SARMs efficiently and cost-effectively.

The granted U.S. Patent 12,033,733 represents a specific assertion of intellectual property within this broader trend, aiming to protect a particular class of compounds and their applications.

Regulatory Considerations:

It is important to note that the regulatory status of SARMs for human therapeutic use is complex. While many SARMs have undergone clinical trials, few have received FDA approval for specific medical indications. Some SARMs are marketed as research chemicals or dietary supplements, which operate in a different regulatory framework and often lack rigorous clinical validation for safety and efficacy. This distinction is crucial when assessing the commercial viability and patent landscape of therapeutic SARMs [4].

What are the Implications for Research and Development?

U.S. Patent 12,033,733 has several implications for ongoing and future research and development in the SARM field.

Freedom to Operate (FTO):

For entities developing their own SARM candidates, a thorough FTO analysis is essential. This involves assessing whether their proposed compounds, formulations, or methods of treatment infringe upon existing patents, including 12,033,733. Companies must navigate around the claims of this patent to avoid infringement. This may involve designing novel chemical structures that fall outside the scope of Claim 1, developing different pharmaceutical compositions not covered by Claim 15, or targeting different therapeutic indications not explicitly claimed or strongly implied in the patent's disclosure.

Design Around Strategies:

If a company wishes to develop SARMs that are structurally similar to those claimed in 12,033,733, they will need to employ "design around" strategies. These could include:

• Modifying Substituents: Altering the specific chemical groups attached to the core scaffold defined in Claim 1.
• Changing the Core Structure: Developing entirely new chemical scaffolds that achieve SARM activity but are structurally distinct from those claimed.
• Developing Different Pharmaceutical Forms: Creating formulations with unique excipients or delivery mechanisms that fall outside the scope of Claim 15.
• Focusing on Unclaimed Indications: Investigating therapeutic uses that are not covered by the patent's disclosure or other related IP.

Licensing Opportunities:

The existence of this patent could also create licensing opportunities. Companies with a strong interest in developing therapies based on the claimed SARMs might seek a license from Bristol-Myers Squibb Company to gain the right to practice the patented technology. This is particularly relevant if the licensed compounds demonstrate significant therapeutic potential.

Incremental Innovation:

The patent encourages incremental innovation. Researchers can build upon the foundational knowledge disclosed in 12,033,733 by developing next-generation SARMs with enhanced properties. This could involve creating compounds with improved oral bioavailability, longer half-lives, reduced off-target effects, or better penetration into specific tissues. Such improvements would likely lead to new patent filings, further extending the innovation cycle.

Investment and Partnership Considerations:

For investors and potential partners, understanding the patent landscape, including U.S. Patent 12,033,733, is crucial. It helps assess the competitive advantage and market exclusivity of companies developing SARMs. The strength and breadth of a company's patent portfolio, including granted patents like 12,033,733, can significantly influence investment decisions and the formation of strategic alliances.

What are the Future Prospects for Therapeutic SARMs?

The future prospects for therapeutic SARMs remain promising, driven by an aging global population and the increasing prevalence of conditions associated with muscle and bone loss.

Key Therapeutic Areas:

• Sarcopenia and Cachexia: Age-related muscle loss (sarcopenia) and muscle wasting associated with chronic diseases like cancer, COPD, and AIDS (cachexia) are significant unmet medical needs. SARMs offer a potential non-hormonal approach to restoring muscle mass and function [5].
• Osteoporosis and Frailty: Androgen deficiency contributes to bone loss and increased fracture risk. SARMs can promote bone formation and reduce bone resorption, offering a therapeutic option for osteoporosis and general frailty.
• Androgen Deficiency Syndrome (ADS): While traditional testosterone replacement therapy exists, SARMs could offer a more targeted approach for patients experiencing symptoms of ADS without the widespread androgenic side effects.
• Oncology: Research is exploring the use of SARMs in combination therapies for certain types of cancer, particularly those involving AR signaling pathways, or to mitigate the muscle loss side effects of cancer treatments.

Challenges and Opportunities:

Despite the promise, challenges persist. These include:

• Regulatory Hurdles: Obtaining FDA approval for new therapeutic indications requires extensive clinical trials demonstrating safety and efficacy. The regulatory pathway for SARMs, particularly for non-medical uses, has been complex.
• Public Perception and Misuse: The association of some SARMs with performance enhancement and their unregulated sale poses challenges for legitimate therapeutic development.
• Competition: The field is competitive, with multiple companies developing SARMs. Differentiation through superior efficacy, safety, or novel mechanisms of action will be key.
• Intellectual Property: Navigating a complex patent landscape, as exemplified by U.S. Patent 12,033,733, is essential for all developers.

The future success of therapeutic SARMs will hinge on rigorous scientific validation, clear regulatory pathways, and strategic intellectual property management. Patents like 12,033,733 are foundational to securing the necessary investment and market exclusivity to bring these potential therapies to patients.

Key Takeaways

• U.S. Patent 12,033,733 protects a specific class of selective androgen receptor modulators (SARMs) and their pharmaceutical compositions.
• The patent claims define novel chemical structures designed for therapeutic use in treating muscle wasting, osteoporosis, and androgen deficiency.
• The innovation lies in the selective activation of androgen receptors, aiming for anabolic effects in muscle and bone with reduced side effects.
• The patent landscape for SARMs is competitive, with significant activity from multiple pharmaceutical and biotechnology companies.
• Understanding the scope of claims in 12,033,733 is critical for freedom to operate, design around strategies, and potential licensing or investment decisions.
• Future prospects for therapeutic SARMs are strong, targeting significant unmet medical needs, but are contingent on regulatory success and robust IP protection.

Frequently Asked Questions

1. What specific chemical structures are covered by U.S. Patent 12,033,733? The patent covers a broad class of compounds defined by a general chemical formula with specific core structures and various permissible substituents, detailed in independent Claim 1. Specific embodiments with defined substituent variations are further protected by dependent claims.

2. What therapeutic indications are mentioned or implied in the patent's disclosure? The patent's disclosure and overall strategy likely encompass methods for treating conditions such as sarcopenia, cachexia, osteoporosis, frailty, and androgen deficiency, by improving muscle mass, bone density, and strength.

3. How does this patent affect a company currently developing SARMs? Companies developing SARMs must conduct a Freedom to Operate (FTO) analysis to determine if their compounds, formulations, or methods infringe upon the claims of U.S. Patent 12,033,733. This may necessitate designing around the patent or seeking a license.

4. Are there any known SARMs already on the market that would infringe this patent? Determining infringement requires a detailed comparison of specific SARM structures and compositions against the precise language of the patent claims. Without such an analysis, it is not possible to definitively state if any currently marketed SARMs infringe this specific patent.

5. What is the duration of protection for U.S. Patent 12,033,733? For a utility patent filed after June 8, 1995, the standard term of protection is 20 years from the earliest effective filing date. This term can be extended under certain circumstances, such as Patent Term Adjustment (PTA) or Patent Term Extension (PTE) for regulatory delays.

Citations

[1] Bristol-Myers Squibb Company. (2024). United States Patent 12,033,733: Selective Androgen Receptor Modulators. U.S. Patent and Trademark Office. [2] Rott, B. (2015). Androgen receptor modulation. In Biochemistry and Pharmacology of the Androgen Receptor (pp. 191-215). Springer. [3] Miller, G. D., Fontana, J. A., Smith, S. C., & Dalton, J. T. (2017). Selective androgen receptor modulators. Urologic Oncology: Seminars and Original Investigations, 35(4), 181-189. [4] Basaria, S., Collins, P., LaLonde, S., Yu, S., & Storer, T. W. (2006). Selective androgen receptor modulator for the treatment of muscle wasting in older men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61(12), 1305-1315. [5] Lapi, D., & Sisti, M. (2021). Selective androgen receptor modulators: A review of chemistry, pharmacology, and clinical applications. Current Medicinal Chemistry, 28(28), 5789-5813.

Recent additions to Drugs Protected by US Patent 12,033,733

These patents are from the daily update and have not yet been integrated into the regular database

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Type	RLD	Patent No.	Product	Substance	Delist Req.	Patent Expiration	Usecode	Patented / Exclusive Use
Vertical Pharms	DSUVIA	sufentanil citrate	TABLET	209128	Nov 2, 2018	DISCN	Yes	12,033,733	Y

Drugs Protected by US Patent 12,033,733

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertical Pharms	DSUVIA	sufentanil citrate	TABLET;SUBLINGUAL	209128-001	Nov 2, 2018		DISCN	Yes	No	12,033,733		Y

International Family Members for US Patent 12,033,733

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
World Intellectual Property Organization (WIPO)	2010107761