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
Stira	DIMETHYL SULFOXIDE	dimethyl sulfoxide	SOLUTION;INTRAVESICAL	220173-001	Jul 7, 2026	AT	RX	No	No
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	10,183,004
Ph Health	GLYCEROL PHENYLBUTYRATE	glycerol phenylbutyrate	LIQUID;ORAL	205742-001	Dec 2, 2021	AA	RX	No	No
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	10,183,003
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	9,254,278

Market dynamics and patent landscape for NLM MeSH Cryoprotective Agents: who owns the IP, what expires first, and where generics and biosimilars pressure pricing

Last updated: July 16, 2026

Cryoprotective agents (CPAs) used to stabilize cells, tissues, and biologics are dominated by established small molecules and polymers in the organ and cell-transplant supply chain, plus formulation-and-method patents around freeze-thaw handling, container systems, and clinical-grade manufacturing. Competitive pressure is concentrated in “enabling” CPAs (e.g., DMSO and glycerol), while high-margin opportunities cluster in patented formulations and process controls that reduce post-thaw viability loss, contamination risk, and compatibility failures in downstream clinical workflows. Patent estates typically split into three layers: base chemical/process coverage, composition-by-ratio (formulation) coverage, and application-specific handling or container/preservation system coverage.

Because “Cryoprotective Agents” in MeSH spans multiple agent classes and therapeutic ecosystems (hematopoietic cell transplantation, reproductive tissue banking, corneal and other tissue preservation, and biologics stabilization), the patent landscape is inherently fragmented across assignees and jurisdictions. The practical market dynamic is that pricing and supply stability are often driven less by chemical substitution and more by regulatory compliance burden and validated cold-chain and thaw protocols protected by method and system patents.

What are the main cryoprotective agents covered by NLM MeSH, and how does each drive market structure?

Answer: The dominant CPA categories map to (1) penetrating permeating CPAs (e.g., dimethyl sulfoxide, DMSO; glycerol), (2) non-penetrating osmolytes and sugars (e.g., trehalose, sucrose), (3) polymers and macromolecular stabilizers (e.g., PEG-based excipients, hydroxyethyl starch in selected contexts), and (4) specialized preservation media and formulation systems tied to specific tissue or cell types. Market structure depends on whether the agent is broadly substitutable (higher generic pressure) or locked into validated, proprietary formulations and workflows (higher IP and margin).

Penetrating agents: DMSO and glycerol

• DMSO is widely used as the primary CPA in hematopoietic stem cell cryopreservation and other cell banking workflows.
• Glycerol is used in certain cell and tissue preservation contexts and as a component of cryopreservation media.

Market dynamic: chemical substitution risk is high in principle, but procurement and process compatibility often anchor buyers to existing validated supply lines. DMSO also faces manufacturing quality and traceability constraints more than pure IP constraints.

Non-penetrating solutes: trehalose and sucrose

Trehalose and sucrose are used to limit ice damage and osmotic shock during freezing and thawing. These agents show more differentiation in branded preservation media and protected formulations.

Market dynamic: differentiation tends to be in “how it is used” (ratios, adjuncts, viscosity modifiers, and thaw-rate coupling) rather than in trehalose itself.

Polymers and excipients

Polymeric CPAs and cryostabilizing excipients (including PEG and certain polysaccharides/hydrogels, depending on application) appear in proprietary preservation systems for cells and tissues.

Market dynamic: these are frequently packaged into multi-component compositions, where composition and method-of-use patents create meaningful barriers to direct generic substitution.

How do patent estates for cryoprotective agents split across chemicals, formulations, and methods?

Answer: The highest litigation and licensing risk typically concentrates in (1) proprietary cryopreservation media compositions with defined excipient ratios, (2) validated freezing/thaw protocols, and (3) container and handling systems. Base-chemical IP for classic CPAs is generally older and often near-expiry, while newer protection is aimed at performance improvements.

Common patent claim types

1. Composition claims
   • Defined ratios of DMSO/glycerol with non-penetrating solutes and stabilizers
   • Specific pH, buffering agents, and tonicity parameters
   • Viscosity and rheology modifiers tied to post-thaw cell viability
2. Method claims
   • Freeze rates, hold temperatures, and thawing profiles
   • Steps to reduce osmotic shock and improve viability
   • Contamination reduction and processing steps
3. System and kit claims
   • Multi-vial or tray systems
   • Coupled “media + container + protocol” packages
4. Manufacturing and QC method claims
   • How the media is produced, filtered, sterilized, and released
   • Stability testing regimes

Where “generic” pressure actually shows up

• True generic substitution is strongest for base CPAs that are not tightly tied to protected compositions.
• Functional substitution is harder when patents cover the composition-by-ratio and method-of-use steps that materially influence viability and clinical performance.

When do key cryoprotective agent patents lose exclusivity, and what drives the timeline?

Answer: Exclusion timelines vary by assignee and by whether protection is for an old base chemical, a newer formulation, or a method tied to a clinical workflow. For buyers, the decisive factor is the earliest-to-expire item in the “composition + method” bundle for the specific application.

Typical exclusivity patterns

• Base chemical protection: older filings, earlier expiries, lower practical exclusivity.
• Formulation and process protection: later filings, extended runway through multiple continuation families and divisionals.
• Regulatory exclusivity: often not the dominant lever for CPAs, because these agents are frequently used as components rather than standalone “new drug” products with classic FDA exclusivity bars. Instead, patents control.

Practical impact for market entry planning

• If a target product is governed by a single-agent CPA (e.g., DMSO), entry barriers are mainly quality and process qualification rather than patent expiration.
• If the target is a proprietary cryopreservation medium or kit (multi-component), barriers persist until composition and method patents expire or are designed around.

What Orange Book status exists for cryoprotective agents, and is FDA exclusivity a gating factor?

Answer: Many CPAs used in cell and tissue workflows are sold as excipients, drug products, or components in preservation systems. Orange Book listings are not always the dominant control point because cryopreservation products often operate outside the “single active ingredient NDA” structure.

Operational gating factor: whether the specific cryopreservation medium is approved as a drug product or is marketed as a component kit. When Orange Book listings exist for a drug product containing an active CPA, they can signal patent expirations that affect generic timelines, but in many CPA ecosystems the practical gating is patent estate and clinical process validation rather than statutory FDA exclusivity.

Which companies own major patent estates for cryoprotective agents and cryopreservation media?

Answer: Ownership is distributed across cell therapy manufacturing and tissue preservation suppliers, with additional IP from excipient and preservation-media specialists. The patent landscape is concentrated in portfolios tied to:

• hematopoietic cell transplantation (HCT) cryopreservation workflows,
• reproductive tissue banking,
• tissue preservation (including corneal and similar applications),
• and biologics stabilization media used in cryo-storage.

Actionable market insight: buyers seeking supply leverage should map patents to the exact intended application (cells vs tissues, clinical vs research use, container format) because portfolios differ sharply by use-case. A DMSO-focused portfolio may not translate to trehalose-sucrose formulation systems for tissue.

What patent litigation and Paragraph IV risks exist for cryoprotective agents?

Answer: Paragraph IV plays are less common for CPAs than for therapeutics with clear FDA-approved, single-active-ingredient generic paths. Where litigation emerges, it usually involves:

• proprietary cryopreservation media compositions,
• method claims tied to validated cryo-thaw handling protocols,
• and patents covering kits or systems that package CPA media with specialized processing steps.

Risk hotspot: entering a branded, multi-component cryopreservation medium market without a freedom-to-operate (FTO) that covers both composition and method claims.

How strong is the patent estate for cryoprotective agents: what claims are hardest to design around?

Answer: The strongest estates are those with:

• narrow but high-impact composition claims (specific excipient ratios, pH/osmolality ranges, and stability parameters),
• broad method claims that capture freezing/thawing profiles and step sequences, and
• system claims that lock in packaging or handling.

Design-around is typically easiest for:

• base CPA selection (DMSO vs glycerol) and
• non-claim-covered formulation tweaks that do not reach the claimed ratio windows.

It is hardest for:

• combinations where small changes break viability metrics and also fail to avoid claim language that covers ranges or equivalents,
• and method claims where the “recipe” for thaw and washing is integral to clinical viability.

How do cryoprotective agents compare from a patent-risk perspective: DMSO vs glycerol vs trehalose-based media?

Answer: From an IP-risk standpoint:

• DMSO and glycerol generally have more legacy, broader availability, and more entry constrained by manufacturing and validation than by active patents.
• trehalose/sucrose and polymeric excipient systems are more frequently packaged into proprietary multi-component media and have later formulation and method patents, producing higher patent-risk on “kit-like” products.

What formulation and delivery system patents protect cryopreservation media, and what do they cover?

Answer: Cryopreservation media patents usually cover how CPA components are combined and managed for freeze-thaw survival.

Typical protected attributes

• Defined CPA concentrations (penetrating and non-penetrating components)
• Buffer system and ionic strength
• Osmolality and pH targets
• Cryostabilizer adjuncts to reduce aggregation or membrane rupture
• Antioxidants or stress protectants when used in specific workflows
• Packaging and storage conditions (e.g., compatibility with container materials)

What method-of-use patents govern freezing and thawing protocols for CPA-containing media?

Answer: Method-of-use patents frequently capture:

• specific cooling/freezing rates (or controlled-rate freezing profiles),
• intermediate hold temperatures,
• thaw temperature ranges and thaw-time targets,
• washing steps to remove CPA/osmotic agents,
• and post-thaw recovery and handling processes.

Commercial implication: protocol differences can be harder to change than composition. If method claims are broad, even sourcing a different CPA vendor may not clear infringement risk.

What generic entry risks exist for cryoprotective agent products used in cell therapy supply chains?

Answer: Generic entry risks concentrate on whether a generic can be proven “equivalent” not only chemically but functionally within the claimed method steps.

Common entry failure modes

• Changing CPA ratio triggers method claim coverage via alternative ranges
• Changing thaw protocol violates “equivalent steps” in asserted method claims
• Using different container or device affects compliance with system claims
• Post-thaw viability drops lead to inability to satisfy clinical or manufacturing acceptance criteria, reducing practical equivalence

How do FDA regulatory pathways affect cryoprotective agent commercialization?

Answer: When CPAs are marketed as components or excipients in approved drug products or as components in regulated cell therapy manufacturing workflows, regulatory treatment is tied to the overall product and manufacturing controls. For vendors, the primary barrier is establishing compatibility with GMP workflows and meeting sterility/endotoxin and stability requirements rather than pursuing exclusivity-based differentiation.

Commercial dynamic: buyers often dual-source but remain aligned to validated protocols that are consistent with clinical lot release, which reduces swap risk even when chemical alternatives exist.

Key commercial dynamics: what moves demand for cryoprotective agents?

Demand drivers

• Growth in cell therapy and hematopoietic stem cell transplantation logistics
• Expansion of tissue banking (reproductive and donor tissue)
• Need for validated cryostorage stability with reduced post-thaw contamination and variability

Supply-side dynamics

• Quality and traceability capability (endotoxin, sterility, particle counts, stability)
• Cold-chain logistics and container compatibility
• Manufacturing scale and regulatory compliance

Price dynamics

• Base CPAs face commodity-like pressure when not locked into protected compositions.
• Proprietary multi-component cryopreservation media and kits maintain pricing power when method and composition patents restrict direct substitution.

Key takeaways

• Patent risk in cryoprotective agents is concentrated in formulation-by-ratio and method-of-use claims tied to cryopreservation workflows, not in base chemical names alone.
• Competitive pressure on classic CPAs (e.g., DMSO, glycerol) is more constrained by GMP qualification and protocol validation than by strict, enforceable chemical exclusivity.
• The highest-value IP and licensing targets are cryopreservation media compositions and coupled systems that cover freeze-thaw handling and storage compatibility.
• Orange Book and FDA exclusivity are not always the primary controls in CPA markets; patents and validated manufacturing protocols tend to be the real gating factors.

FAQs

1. Do cryoprotective agent patents cover freezing rates and thaw protocols, or only media compositions?
   Method claims often cover freeze and thaw profiles plus step sequences (hold points, thaw temperature/time, and post-thaw washing/recovery), while composition claims cover CPA ratios, buffers, and osmolality targets.

2. Can a generic replace DMSO in cryopreservation without infringing formulation or method patents?
   Replacement can still create infringement risk if asserted claims cover the broader cryopreservation media composition ranges or the method steps performed during processing.

3. Are trehalose-based cryoprotective media more IP-protected than DMSO?
   Trehalose and polymer/sugar systems are more often embedded in proprietary multi-component media and protected by later formulation and method patents.

4. What creates the biggest barrier to entry for new CPA suppliers: patents or regulatory qualification?
   For generic chemical substitution, regulatory and validation are often the main hurdle; for branded cryopreservation media and kits, patents that cover composition plus method steps are the key barrier.

5. Where should patent mapping start for a new cryopreservation medium launch?
   Start with application-specific portfolios: the exact cryopreservation medium composition family and the validated processing steps used in the target clinical or tissue banking workflow.

References (APA)

1. U.S. National Library of Medicine. MeSH (Medical Subject Headings). “Cryoprotective Agents.”
2. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.
3. U.S. Patent and Trademark Office. Patent assignment and bibliographic records (public PAIR/Early data as applicable).