Mechanism of Action: Cystine Disulfide Reduction

Drugs with Mechanism of Action: Cystine Disulfide Reduction

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Horizon	PROCYSBI	cysteamine bitartrate	CAPSULE, DELAYED RELEASE;ORAL	203389-001	Apr 30, 2013		RX	Yes	No	10,548,859*PED				Y
Horizon	PROCYSBI	cysteamine bitartrate	CAPSULE, DELAYED RELEASE;ORAL	203389-002	Apr 30, 2013		RX	Yes	Yes	10,905,662*PED				Y
Leadiant Biosci Inc	CYSTARAN	cysteamine hydrochloride	SOLUTION/DROPS;OPHTHALMIC	200740-001	Oct 2, 2012		RX	Yes	Yes
Mylan	CYSTAGON	cysteamine bitartrate	CAPSULE;ORAL	020392-001	Aug 15, 1994		RX	Yes	No
Mylan	CYSTAGON	cysteamine bitartrate	CAPSULE;ORAL	020392-002	Aug 15, 1994		RX	Yes	Yes
Recordati Rare	CYSTADROPS	cysteamine hydrochloride	SOLUTION/DROPS;OPHTHALMIC	211302-001	Aug 19, 2020		RX	Yes	Yes

Cystine Disulfide Reduction Market Analysis and Financial Projection

The market dynamics and patent landscape for drugs targeting cystine disulfide reduction are shaped by innovations in therapeutic applications, expanding pharmaceutical markets, and strategic intellectual property protections. Below is a detailed breakdown:

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Market Dynamics

Key Growth Drivers

• Pharmaceutical Industry Expansion: The global cysteine market, valued at $462.13 million in 2024, is projected to grow at a 5.8% CAGR, driven by cysteine’s role in drug synthesis (e.g., disulfide bond reduction in antibodies) and treatments for conditions like cystinosis[2]. Emerging markets like India (projected pharmaceutical revenue: $65 billion by 2024) and Germany (€58.8 billion in 2021 drug sales) are major contributors[2].
• Cystinosis Treatment Demand: Oral cysteamine (e.g., Procysbi) remains the standard therapy for nephropathic cystinosis. The global cystinosis treatment market is projected to exceed $700 million by 2030, driven by increased diagnosis rates and delayed-release formulations that improve compliance[15][16].
• Antibody-Drug Conjugate (ADC) Development: Over 150 ADCs are in clinical trials, with disulfide reduction critical for drug conjugation. Innovations like electrocatalytic reduction (97% efficiency in antibody cleavage) enhance ADC manufacturing scalability[1][7].

Challenges

• Toxicity Management: ADC therapies face dose-limiting toxicities, necessitating optimized linker technologies and payloads[7].
• Cost and Accessibility: High prices for orphan drugs (e.g., Procysbi) and limited generics due to patent protections impede broader access[4][14].

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Patent Landscape

Procysbi (Cysteamine Bitartrate)

• Patent Protections: Protected by 12 US patents, with key patents (e.g., US 9,198,882) covering delayed-release formulations until 2034–2037. Pediatric exclusivity extensions further delay generic entry[4][13][14].
• Litigation and Challenges: Two Paragraph IV certifications have been filed, but generics face hurdles due to complex formulation patents and ongoing legal disputes[4][14].

Disulfide Reduction Technologies

• Antibody Engineering: Patents like US8574869B2 address disulfide stabilization in antibody production, crucial for ADC efficacy[6].
• Reduction Methods: Patent WO2004101597A2 covers dithiol-based reducers (e.g., DTT alternatives) for disulfide cleavage in peptides and proteins[11].

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Emerging Trends

• Personalized Medicine: Tailored cysteamine dosing and novel formulations (e.g., NACMEAA dithiols) aim to minimize side effects while maintaining efficacy[5][16].
• ADC Innovation: Electrocatalytic reduction methods enable precise disulfide cleavage in antibodies like Zilovertamab, streamlining ADC synthesis[1].

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Key Players

• Cysteine Suppliers: Wacker Chemie AG, Merck KGaA, and Ajinomoto dominate the cysteine market[2].
• Cystinosis Therapies: Horizon Therapeutics (Procysbi) leads, with generics awaiting patent expirations post-2034[4][14].

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Highlight: "Electrocatalytic reduction of Zilovertamab achieves 97% conversion efficiency, enabling scalable ADC production."[1]

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This landscape reflects a balance between innovation in therapeutic applications and robust intellectual property strategies, with significant growth opportunities in rare disease treatments and biologics manufacturing.

References

1. https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ce3e75e9ebbb4db96e913b/original/20240215_Disulfides_Reduction_print.pdf
2. https://www.stellarmr.com/report/Cysteine-Market/845
3. https://www.epo.org/en/boards-of-appeal/decisions/t190031eu1
4. https://www.drugpatentwatch.com/p/tradename/PROCYSBI
5. https://pubs.acs.org/doi/10.1021/acs.joc.2c01050
6. https://patents.google.com/patent/US8574869B2/en
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC10655051/
8. https://digital.csic.es/bitstream/10261/239124/3/202000092.pdf
9. https://www.elsevier.com/resources/clinicalkey-ai/what-is-the-treatment-for-nephropathic-cystinosis-b907
10. https://www.jci.org/articles/view/108448/citations
11. https://patents.google.com/patent/WO2004101597A2/en
12. https://drugcentral.org/drugcard/768
13. https://www.drugpatentwatch.com/p/patent/9198882
14. https://pharsight.greyb.com/drug/procysbi-patent-expiration
15. https://github.com/roceljiabur/Market-Research-Report-List-1/blob/main/cystinosis-treatment-market-global-outlook-and-forecast-2022-2028-market.md
16. https://sites.google.com/view/benchmark-capitals/home/top-trending-reports/cystinosis-treatment-market-key-insights-and-future-projections