US Patent 10,143,665: Cysteamine Bitartrate Patent Scope, Claims, Expiration and Generic Risk

US Patent 10,143,665 protects specific methods of treating cystinosis with twice-daily oral cysteamine bitartrate formulations that satisfy impurity limits and are stored under refrigerated conditions. The patent is directed to product quality and administration of cysteamine bitartrate, not to cysteamine bitartrate as a molecule.

The strongest commercial relevance is for delayed-release cysteamine bitartrate products such as Procysbi. A competing product may avoid infringement if it does not satisfy every limitation of at least one independent claim, particularly the impurity threshold, twice-daily dosing, or 2° C. to 8° C. storage limitation.

What does US Patent 10,143,665 protect?

The patent contains four independent method claims and four dependent claims. Each independent claim requires:

Treatment of cystinosis.
A subject in need of treatment.
Twice-daily administration.
An oral pharmaceutical composition containing cysteamine bitartrate.
A specified impurity below a quantitative threshold.
Storage of the composition at approximately 2° C. to 8° C. before administration.

Independent claim	Controlled impurity	Maximum amount relative to cysteamine bitartrate	Additional limitation
Claim 1	2-Hydroxythiomorpholine	Less than 0.5%	Refrigerated storage
Claim 3	Cystamine	Less than 4%	Refrigerated storage
Claim 5	Cystamine tartrate amide	Less than 0.5%	Refrigerated storage
Claim 7	2-Hydroxymethylthiazolidine	Less than 0.05%	Refrigerated storage

Claims 2, 4, 6 and 8 add an enteric coating comprising poly(methacrylic acid co-ethyl acrylate) 1:1.

The claims therefore form four alternative impurity-based infringement pathways. A product need not contain all four impurities to fall within the patent. It may implicate one claim set if it contains cysteamine bitartrate, is administered twice daily for cystinosis, is stored at the specified temperature, and satisfies the relevant impurity limitation.

How broad are the independent claims?

The claims are method claims, not composition claims. This distinction limits their direct enforcement against manufacturers.

A method claim generally requires proof that the claimed treatment method was practiced. Potential defendants include:

The product manufacturer, where its labeling or instructions encourage the claimed use.
A distributor or supplier that induces the claimed use.
A healthcare provider or patient, although commercial patent disputes normally focus on induced or contributory infringement by commercial actors.

The claims do not expressly require:

A particular dosage strength.
A particular capsule size.
A particular patient age.
A particular baseline leukocyte cystine level.
A specific clinical response.
A particular brand.
A particular manufacturing process.
A particular amount of cysteamine per dose.
A particular number of capsules per administration.

The absence of a dosage-strength limitation increases the potential breadth of the claims. The requirement for twice-daily administration narrows them against products labeled for other dosing schedules.

Claim 1 and 2: 2-Hydroxythiomorpholine

Claim 1 covers cysteamine bitartrate compositions containing less than 0.5% 2-hydroxythiomorpholine relative to cysteamine bitartrate. Claim 2 adds the specified enteric coating.

The threshold is comparatively broad relative to the 2-hydroxymethylthiazolidine threshold in claim 7. A product with a detectable amount of 2-hydroxythiomorpholine may still fall within claim 1 if the amount remains below 0.5%.

Claim 3 and 4: cystamine

Claim 3 covers compositions containing less than 4% cystamine relative to cysteamine bitartrate. Claim 4 adds the enteric coating.

Because the threshold is 4%, this claim set may cover a wider range of impurity profiles than the claims directed to cystamine tartrate amide or 2-hydroxymethylthiazolidine. Analytical testing and the patent’s interpretation of the relative amount would be central to any dispute.

Claim 5 and 6: cystamine tartrate amide

Claim 5 uses a lower 0.5% threshold for cystamine tartrate amide. Claim 6 adds the enteric coating.

This claim set focuses on a particular degradation or reaction product rather than total cystamine. A product may avoid claim 5 while still raising issues under claim 3 if the relevant cystamine level is below 4%.

Claim 7 and 8: 2-hydroxymethylthiazolidine

Claim 7 has the narrowest numerical threshold: less than 0.05% 2-hydroxymethylthiazolidine. Claim 8 adds the enteric coating.

The lower threshold may make this claim commercially important where the formulation process produces trace levels of the impurity. It also creates a potentially significant analytical issue because the dispute may turn on assay sensitivity, validated methods, sampling procedures and batch-to-batch variation.

What formulations are protected by US 10,143,665?

The dependent claims protect an oral cysteamine bitartrate formulation with an enteric coating comprising poly(methacrylic acid co-ethyl acrylate) 1:1.

This polymer is commonly associated with pH-dependent enteric release systems. The coating is relevant because cysteamine has gastrointestinal tolerability issues and delayed release can affect administration and adherence.

The patent does not appear, from the supplied claims, to require:

A specific coating weight gain.
A specific particle size.
A specific dissolution profile.
A specific capsule shell.
A specific plasticizer.
A specific manufacturing temperature.
A particular dosage strength.

The coating limitation is narrower than the independent claims. A product using a different enteric polymer may avoid the dependent claims while remaining exposed to one of the independent claims.

Formulation elements that may create infringement risk

Formulation characteristic	Relevance to the '665 claims
Cysteamine bitartrate active ingredient	Required by every independent claim
Oral dosage form	Required by every independent claim
Twice-daily label	Required by every independent claim
Storage at 2° C. to 8° C. before administration	Required by every independent claim
Poly(methacrylic acid co-ethyl acrylate) 1:1	Required only by dependent claims
Impurity testing	Determines which independent claim may apply
Immediate-release formulation	May avoid the enteric-coating claims, but not necessarily the independent claims
Alternative cysteamine salt	May avoid the claims if the product is not cysteamine bitartrate

When does US Patent 10,143,665 expire?

US Patent 10,143,665 issued on November 27, 2018. The enforceable expiration date depends on the patent’s earliest effective nonprovisional priority date, any patent term adjustment, and any terminal disclaimer.

A patent’s issue date does not establish its expiration date. For a US utility patent, the baseline term generally runs 20 years from the earliest effective US nonprovisional or international filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156.

The patent should therefore be evaluated through the USPTO Patent Center record for:

Earliest effective priority date.
Patent term adjustment.
Terminal disclaimers.
Continuation or divisional relationships.
Any patent term extension.
Assignment history.

The claims supplied do not establish a definitive expiration date. An accurate expiration conclusion cannot be drawn from the claim text alone.

Is US 10,143,665 an Orange Book patent?

The commercial relevance of the '665 patent depends in part on whether it is listed in the FDA Orange Book against a cysteamine bitartrate product, particularly Procysbi.

Orange Book listing normally requires that the patent claim the drug substance, drug product, or an approved method of use. The '665 claims are method-of-use claims because they require treatment of cystinosis with twice-daily administration.

The relevant listing questions are:

Orange Book issue	Analysis
Drug-substance patent	The claims do not claim cysteamine bitartrate as a chemical compound
Drug-product patent	The independent claims are not conventional composition claims
Method-of-use patent	Yes, based on the claimed cystinosis treatment method
Formulation protection	Present in dependent claims through the enteric coating limitation
Paragraph IV exposure	Potentially relevant if the patent is listed against an approved reference product
Label carve-out	A generic applicant may attempt to omit the patented twice-daily cystinosis use, subject to FDA approval and infringement risk

An Orange Book listing is a regulatory record question separate from claim scope. FDA listing status should be confirmed against the current Orange Book patent table for the relevant NDA.

How does the patent affect Paragraph IV challenges?

A generic applicant seeking approval for a cysteamine bitartrate product may file a Paragraph IV certification if it believes the patent is invalid, unenforceable or not infringed.

Potential Paragraph IV positions include:

The proposed product does not contain one of the claimed impurities below the specified threshold.
The product is not labeled for twice-daily treatment of cystinosis.
The product is not stored at 2° C. to 8° C. before administration.
The product does not contain cysteamine bitartrate.
The product does not use the specified enteric coating.
The patent is invalid for anticipation or obviousness.
The claims are indefinite because terms such as “about,” “relative to,” or the storage limitation lack sufficient precision.
The patent is unenforceable because of inequitable conduct or other litigation-specific defenses.

The strongest noninfringement strategy is usually a design-around that changes more than one limitation. For example, a product could use a different salt, a different active pharmaceutical ingredient form, a non-refrigerated storage condition, and a label that does not direct twice-daily cystinosis treatment. Changing only the coating may avoid claims 2, 4, 6 and 8 while leaving claims 1, 3, 5 and 7 potentially relevant.

What patent litigation affects cysteamine bitartrate products?

The claims create a litigation framework centered on product testing and labeling rather than a simple comparison of active ingredients.

A patent dispute would likely examine:

Batch records.
Stability data.
Certificate of analysis documentation.
Validated impurity assays.
Storage and distribution records.
Proposed generic labeling.
Dissolution testing.
Coating composition.
Manufacturing specifications.
Product samples obtained from the market.
Whether the relevant impurity is measured as a percentage by mass, molar percentage or another basis.

For a generic applicant, the most important evidence would be its final commercial formulation and its proposed FDA labeling. For the patent owner, the most important evidence would be the product’s actual impurity profile and the extent to which the label directs twice-daily use for cystinosis.

No litigation outcome, settlement agreement or licensed resolution can be determined from the supplied claim text.

How does US 10,143,665 compare with other cystinosis products?

Procysbi versus Cystagon

Product	Active ingredient	Typical administration concept	Relevance to '665 patent
Procysbi	Cysteamine bitartrate	Delayed-release, twice-daily oral treatment	Closest commercial fit to the claims
Cystagon	Cysteamine bitartrate	Immediate-release, more frequent administration	Less directly aligned with twice-daily and enteric-coating limitations
Generic cysteamine bitartrate	Cysteamine bitartrate	Depends on approved label and formulation	Patent exposure depends on impurity profile, storage and dosing
Cysteamine ophthalmic products	Cysteamine hydrochloride or other cysteamine formulation	Ocular administration	Generally outside these claims

The patent is more relevant to delayed-release, twice-daily cysteamine bitartrate than to conventional immediate-release cysteamine products. The claims do not require “delayed release” in the independent claims, however. A twice-daily oral product could face claim exposure even if it uses a different release mechanism, assuming the other limitations are met.

Does the patent create biosimilar risk?

No conventional biosimilar pathway applies. Cysteamine bitartrate is a small-molecule drug, not a biologic. Competitive products would generally proceed under the Abbreviated New Drug Application pathway or another applicable small-molecule route rather than under the Biologics Price Competition and Innovation Act.

The relevant competitive risks are:

Generic cysteamine bitartrate.
Authorized generic or licensed alternative.
Reformulated cysteamine product.
Different cysteamine salt.
Different dosing schedule.
Alternative enteric-release technology.
Compounded or hospital-use formulations, subject to applicable regulation.

How strong is the patent estate?

The '665 patent has meaningful but targeted protection.

Strengths

Four independent impurity-based claim pathways.
Coverage tied to a commercially relevant twice-daily cysteamine regimen.
Refrigerated-storage limitation that may correspond to product labeling.
Dependent claims directed to a recognizable enteric-coating polymer.
Quantitative impurity limits that can be tested analytically.

Weaknesses

The claims are method claims rather than broad composition claims.
Infringement requires proof of every limitation.
The storage limitation may create a factual dispute over when and how storage occurred.
“Relative to the amount of cysteamine bitartrate” may require claim construction and validated measurement methodology.
A generic applicant may avoid the dependent claims by using a different coating.
A label carve-out may reduce exposure to the twice-daily cystinosis method, depending on the approved indications and actual product use.
The patent does not, from the supplied claims, block every cysteamine product or every cystinosis treatment.

Overall, the patent is strongest against a delayed-release cysteamine bitartrate product that matches the reference product’s dosing, refrigeration, impurity profile and enteric-coating technology. It is weaker against a product that changes the active ingredient form, dosing schedule, storage condition or release technology.

What manufacturing and intellectual-property barriers exist?

The main technical barrier is control of cysteamine degradation and reaction impurities. A competing manufacturer would need to manage:

Raw-material purity.
Oxidation control.
Moisture exposure.
Temperature excursions.
Packaging compatibility.
Coating uniformity.
Long-term stability.
Analytical detection limits.
Refrigerated distribution.
Batch-release specifications.

The claim thresholds make manufacturing control commercially important. A manufacturer may be able to formulate a product with the same active ingredient but still avoid one claim by controlling a particular impurity. Conversely, a product that meets all ordinary release specifications may remain exposed if its measured impurity concentration falls within a claimed range.

The enteric-coating claims increase the design-around value of alternative polymers and coating systems. A different polymer may avoid the dependent claims, but it does not automatically eliminate risk under the independent claims.

What is the likely generic launch risk?

Generic launch scenario	Risk under the '665 patent
Same cysteamine bitartrate, same twice-daily label, refrigerated storage	High
Same active ingredient and dosing, different enteric polymer	Moderate to high
Same active ingredient, immediate-release and more frequent dosing	Lower under these claims
Different cysteamine salt	Potentially lower
Product not refrigerated before administration	Potentially lower
Label omits cystinosis treatment or twice-daily use	Lower, subject to actual use and induced-infringement analysis
Impurity profile exceeds a claimed threshold	Potentially lower for that claim
Product contains no cysteamine bitartrate	Outside the literal active-ingredient limitation

The largest commercial exposure is for an ANDA product designed to replicate the formulation, storage instructions and twice-daily use of an approved delayed-release cysteamine bitartrate product.

Does the patent support licensing or settlement leverage?

Yes. The patent can support licensing leverage where a competing product needs to replicate:

Twice-daily cysteamine treatment.
Refrigerated storage.
The reference product’s impurity specifications.
An enteric coating based on poly(methacrylic acid co-ethyl acrylate) 1:1.

Its value is narrower than a composition patent because a competitor may have formulation and labeling design-around options. The strongest settlement leverage would arise if the patent is listed in the Orange Book, survives a Paragraph IV challenge, and is supported by additional patents covering delayed release, capsule architecture, manufacturing processes or broader cysteamine formulations.

No specific license, covenant not to sue or settlement agreement is established by the claims provided.

Key Takeaways

US Patent 10,143,665 protects four cysteamine bitartrate treatment methods for cystinosis.
Each independent claim requires twice-daily oral administration and storage at approximately 2° C. to 8° C. before administration.
The four independent claims target separate impurity thresholds.
Claims 2, 4, 6 and 8 add an enteric coating comprising poly(methacrylic acid co-ethyl acrylate) 1:1.
The patent is most relevant to Procysbi-type delayed-release cysteamine bitartrate products.
It is not a broad patent on cysteamine, cysteamine bitartrate or all cystinosis treatments.
Generic risk depends heavily on labeling, storage instructions, impurity testing and formulation design.
The claims create no conventional biosimilar issue because cysteamine bitartrate is a small-molecule drug.
A definitive expiration date, Orange Book listing status and current litigation position require the underlying USPTO, FDA and court records rather than the claim text alone.

FAQs About US Patent 10,143,665

Does US 10,143,665 cover Procysbi?

It may be relevant to Procysbi because the claims correspond to twice-daily oral cysteamine bitartrate, refrigerated storage and enteric-coated formulations. Product-specific infringement and Orange Book conclusions require comparison with the approved label, formulation specifications and FDA patent listing.

Can a generic cysteamine product avoid this patent by using a different coating?

A different coating may avoid claims 2, 4, 6 and 8. It does not by itself avoid claims 1, 3, 5 or 7, which do not require the specified enteric coating.

Is the 2° C. to 8° C. storage requirement a major limitation?

Yes. It is present in every independent claim. A product and labeling strategy that does not require storage within that range may have a significant noninfringement position, subject to the product’s actual distribution and storage conditions.

Does the patent cover immediate-release Cystagon?

The claims do not expressly require delayed release, so an immediate-release product is not automatically outside their scope. The twice-daily dosing, refrigerated storage, cysteamine bitartrate composition and impurity limitations would still need to be analyzed.

What is the most important validity issue?

The principal technical issues are likely to involve prior-art disclosure of cysteamine bitartrate formulations, impurity limits, refrigerated storage and twice-daily cystinosis treatment. Claim construction of the impurity measurement basis and the storage limitation may also materially affect validity and infringement.

References

United States Patent and Trademark Office. (2018). U.S. Patent No. 10,143,665. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (n.d.). Procysbi prescribing information. Silver Spring, MD: U.S. Department of Health and Human Services.
United States Code, 35 U.S.C. §§ 154, 156, 271 and 282.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions and Paragraph IV patent certifications. Silver Spring, MD: U.S. Department of Health and Human Services.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Horizon	PROCYSBI	cysteamine bitartrate	CAPSULE, DELAYED RELEASE;ORAL	203389-001	Apr 30, 2013		RX	Yes	No	10,143,665*PED	⤷ Start Trial			Y		⤷ Start Trial
Horizon	PROCYSBI	cysteamine bitartrate	CAPSULE, DELAYED RELEASE;ORAL	203389-002	Apr 30, 2013		RX	Yes	Yes	10,143,665*PED	⤷ Start Trial			Y		⤷ Start Trial
Horizon	PROCYSBI	cysteamine bitartrate	GRANULE, DELAYED RELEASE;ORAL	213491-001	Feb 14, 2020		RX	Yes	No	10,143,665*PED	⤷ Start Trial			Y		⤷ Start Trial
Horizon	PROCYSBI	cysteamine bitartrate	GRANULE, DELAYED RELEASE;ORAL	213491-002	Feb 14, 2020		RX	Yes	Yes	10,143,665*PED	⤷ Start Trial			Y		⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 10,143,665

Which drugs does patent 10,143,665 protect, and when does it expire?

Summary for Patent: 10,143,665