Drugs in MeSH Category Cryoprotective Agents

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	10,183,003
Mylan Institutional	RIMSO-50	dimethyl sulfoxide	SOLUTION;INTRAVESICAL	017788-001	Approved Prior to Jan 1, 1982		RX	Yes	Yes
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	8,404,215				Y

Market Dynamics and Patent Landscape for Drugs in the NLM MeSH Class: Cryoprotective Agents

Last updated: July 30, 2025

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Introduction

Cryoprotective agents (CPAs) are specialized compounds that protect biological tissue and cells from freezing damage during cryopreservation. Their critical role in biobanking, regenerative medicine, assisted reproductive technologies, and pharmaceuticals has driven substantial research, commercialization, and innovation. Understanding market dynamics and the patent landscape of CPAs is essential for stakeholders—including pharma companies, biotech firms, investors, and policymakers—seeking to capitalize on emerging opportunities and mitigate risks within this niche.

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Market Overview

Growing Global Demand

The cryopreservation market, anchored by cryoprotective agents, is experiencing rapid growth driven by expanding applications in fertility preservation, regenerative therapies, and organ transplantation. According to Market Research Future, the global cryopreservation market is projected to reach USD 24 billion by 2025, with a compound annual growth rate (CAGR) of approximately 16% [1].

Factors fueling this expansion include:

• Increased prevalence of infertility: Rising infertility rates have amplified demand for fertility cryopreservation technologies, notably in sperm, oocyte, and embryo freezing.
• Advancements in regenerative medicine: Cell therapies, stem cell banking, and tissue engineering rely heavily on effective cryoprotection.
• Biopharmaceutical development: Preservation of biologics, vaccines, and recombinant proteins depends on CPAs to maintain stability during storage.

Key Market Segments

Cryoprotectants are primarily categorized into:

• Permeating cryoprotectants: such as dimethyl sulfoxide (DMSO), ethylene glycol, and glycerol, which penetrate cell membranes to prevent intracellular ice formation.
• Non-permeating cryoprotectants: including sucrose and trehalose, which function extracellularly to control ice formation and osmotic stress.

DMSO remains dominant due to its broad efficacy, though concerns over toxicity and side effects are fostering research into safer alternatives.

Market Challenges

Despite robust growth, the market faces obstacles like:

• Toxicity: Conventional CPAs such as DMSO pose toxicity risks, prompting demand for safer, non-toxic compounds.
• Regulatory hurdles: Ensuring compliance across different jurisdictions complicates product development.
• Cost barriers: High costs associated with novel cryoprotectants can hinder widespread adoption.

Emerging Trends

• Development of non-toxic, synthetic CPAs: Focused on improving safety profiles.
• Nanoparticle-based cryoprotectants: Innovative formulations to enhance efficacy.
• Personalized cryopreservation protocols: Tailored approaches based on tissue type and patient profile.

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Patent Landscape Analysis

Historical patent activity

The patent environment for cryoprotective agents reflects a landscape marked by early dominance of proprietary versions of DMSO and glycerol. The late 20th and early 21st centuries saw a surge of patents targeting modifications to reduce toxicity, improve permeability, and enhance cryoprotective efficacy.

Key patent filers include:

• Major biotech and pharmaceutical firms: Such as Thermo Fisher Scientific, Fujifilm, and Merck, which have developed and patented proprietary cryoprotectants.
• Academic institutions: Contributing foundational patents for novel compounds and formulations.
• Emerging startups: Focused on innovative, low-toxicity CPAs and delivery systems.

Patent classifications and innovation hotspots

Most patents in this space are classified under CPC ( Cooperative Patent Classification) codes related to biological material preservation and cryoprotection (e.g., A01N, C12Q).

The dominant themes include:

• Chemical modifications of existing CPAs: To reduce toxicity and increase permeability.
• Novel cryoprotective compounds: Such as antifreeze proteins, synthetic mimetics, and natural osmolytes.
• Advanced delivery systems: Encapsulation, liposomes, and nanoparticles to optimize CPA efficacy.

Patent expiration and freedom-to-operate (FTO) considerations

Patents predating 2010 are nearing expiration, potentially opening avenues for generic development. However, many foundational patents still have multiple years of enforceability, and newer patents, especially those covering innovative formulations and delivery methods, remain active.

Competitive landscape

The landscape is characterized by:

• A handful of large incumbents with broad patent portfolios.
• A burgeoning segment of smaller firms and academia holding niche patents, often focusing on specific tissues or novel compounds.
• An increasing trend toward patent pooling and licensing agreements, indicating the importance of collaborations to navigate complex intellectual property (IP) rights.

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Strategic Considerations for Stakeholders

• Innovation investment: Developing non-toxic, highly permeable CPAs remains essential to differentiate and capture market share.
• IP analysis: Continuous monitoring of patent filings helps identify gaps, avoid infringement, and facilitate licensing negotiations.
• Regulatory pathways: Novel agents must demonstrate safety and efficacy, emphasizing the importance of comprehensive patent datasets in supporting regulatory submissions.
• Collaboration and licensing: Partnering with patent holders can accelerate product development and commercialization.

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Regulatory and Legal Aspects

Regulators like the FDA and EMA scrutinize cryoprotective agents for toxicity and safety. Patentability hinges on demonstrating invention novelty, non-obviousness, and industrial applicability, especially with incremental innovations to existing agents. Patent holders often file additional claims as new formulations and delivery systems are developed to maintain competitive leverage.

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Conclusion

The cryoprotective agents market is dynamically evolving, driven by technological innovation, expanding applications, and regulatory challenges. A strategic understanding of the patent landscape reveals opportunities for differentiation, partnerships, and new product development. Stakeholders must balance ongoing R&D with vigilant patent monitoring to optimize their positioning in this critical segment of biopreservation.

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Key Takeaways

• Market expansion driven by regenerative medicine, fertility preservation, and biopharma needs offers significant growth opportunities.
• DMSO dominance persists but is challenged by toxicity concerns, catalyzing innovation toward safer alternatives.
• Patent activity centers on modifications to existing CPAs, novel compounds, and advanced delivery systems, with expiration timelines influencing market entry strategies.
• Intellectual property management remains crucial, requiring ongoing analysis to avoid infringement and leverage licensing opportunities.
• Regulatory approval depends on demonstrable safety, underscoring the importance of patenting innovative, non-toxic cryoprotectants.

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FAQs

Q1: What are the most commonly used cryoprotective agents today?
DMSO remains the most widely used permeating cryoprotectant, often combined with other agents like glycerol. Non-permeating agents such as sucrose supplement preservation protocols. However, safety concerns are fostering searches for alternatives.

Q2: How does patent law influence innovation in cryoprotective agents?
Patent protections incentivize innovation by securing exclusive rights to new compounds and formulations. However, patent expirations enable generic and research use, impacting market competition.

Q3: Are there emerging alternatives to traditional cryoprotectants?
Yes. Researchers are exploring antifreeze proteins, synthetic osmolytes, and nanoparticle-based systems designed to enhance cryopreservation efficacy while minimizing toxicity.

Q4: What are the key challenges in patenting new cryoprotective agents?
The primary challenges include demonstrating genuine novelty, overcoming prior art, and showing non-obviousness, especially given the extensive research on existing agents.

Q5: How is regulatory approval affecting patent strategies?
Regulatory hurdles necessitate that patented agents demonstrate safety and efficacy, influencing patent claims to encompass not only chemical entities but also their specific uses and delivery methods.

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References

[1] Market Research Future. "Cryopreservation Market Research Report." 2021.