Details for Patent: 9,925,156

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Which drugs does patent 9,925,156 protect, and when does it expire?

Patent 9,925,156 protects PROCYSBI and is included in two NDAs.

Protection for PROCYSBI has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has twenty-nine patent family members in nineteen countries.

Summary for Patent: 9,925,156

Title:	Enterically coated cysteamine, cystamine and derivatives thereof
Abstract:	The disclosure provides oral cysteamine and cystamine formulations useful for treating cystinosis and neurodegenerative diseases and disorders. The formulations provide controlled release compositions that improve quality of life and reduced side-effects.
Inventor(s):	Ranjan Dohil, Jerry Schneider
Assignee:	University of California San Diego UCSD
Application Number:	US15/656,863
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,925,156
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Patent 9,925,156: Scope, Claims, Expiration, and Cystinosis Patent Landscape

U.S. Patent No. 9,925,156 protects oral, enterically coated compositions containing cysteamine bitartrate and cystamine, together with twice-daily treatment methods for nephropathic cystinosis. The core commercial relevance is Procysbi, a delayed-release cysteamine product developed by Raptor Pharmaceuticals and now marketed by Horizon Therapeutics.

The patent is strongest against products that combine the following elements:

1. Cysteamine bitartrate as the active cysteamine source.
2. Cystamine or a pharmaceutically acceptable cystamine salt in the same core.
3. One or more pharmaceutical binders.
4. An enteric coating that begins dissolving at approximately pH 4.5 to 5.5.
5. Oral, twice-daily administration for nephropathic cystinosis.

The patent does not broadly cover every cysteamine product, every enteric-coated formulation, or every treatment of cystinosis. Infringement generally requires meeting all limitations of at least one asserted claim.

What does U.S. Patent 9,925,156 cover?

U.S. Patent 9,925,156 is directed to enterically coated cysteamine compositions and related treatment methods. The independent claims are claim 1, a composition claim, and claims 7 and 11, method claims.

Claim	Category	Principal subject matter
1	Composition	Enterically coated core containing cysteamine bitartrate, cystamine or a salt, and binders
2	Composition	Tablet or granule dosage form
3	Composition	Granules loaded into a capsule
4	Composition	Specified enteric-coating materials
5	Composition	Enteric coating containing a methacrylic acid ester
6	Composition	Oral administration
7	Method	Twice-daily treatment of nephropathic cystinosis
8	Method	100 to 1,000 mg cysteamine free base per administration
9	Method	White-blood-cell cystine below 1 nmol half-cystine/mg protein
10	Method	Approximately 1.35 g/m² total daily free-base dose
11	Method	Lowering cellular cystine in nephropathic cystinosis
12	Method	100 to 1,000 mg cysteamine free base per administration
13	Method	White-blood-cell cystine below the specified threshold
14	Method	Approximately 1.35 g/m² total daily dose

The patent’s commercial center is the combination of formulation and dosing regimen. A competing product would face greater risk if it uses the same active ingredients, the same pH-triggered enteric release profile, and a twice-daily dosing schedule.

What is the scope of independent claim 1?

Claim 1 requires an enterically coated composition comprising four material elements:

• A core.
• Cysteamine bitartrate in the core.
• Cystamine or a pharmaceutically acceptable cystamine salt in the core.
• One or more pharmaceutically acceptable binders in the core.
• An enteric coating encasing the core.
• An enteric coating that begins dissolving in aqueous solution at approximately pH 4.5 to 5.5.

The claim is narrower than a generic delayed-release cysteamine claim because it expressly requires cystamine or a cystamine salt in addition to cysteamine bitartrate. The presence of cystamine may be important during infringement analysis. A formulation containing cysteamine bitartrate but no cystamine may avoid literal infringement of claim 1, unless another claim or an equivalent theory applies.

What does “cystamine or a pharmaceutically acceptable salt” require?

The claim language requires cystamine or a pharmaceutically acceptable salt of cystamine. Cystamine is the disulfide formed by oxidation of cysteamine. The claim does not merely require an impurity profile containing cystamine. A material intended to satisfy the claim would likely need to contain cystamine as a formulation component or otherwise include it in the core.

The claim does not specify a minimum concentration for cystamine. That absence creates a potential dispute over whether a trace amount, residual amount, or process-related amount is sufficient. Courts generally interpret claim terms in light of the specification, prosecution history, and ordinary meaning. The commercial relevance of the cystamine limitation would depend on the patent record and the actual product composition.

What does the pH 4.5 to 5.5 limitation mean?

The coating must begin to dissolve in an aqueous solution at a pH between approximately 4.5 and 5.5. This is a functional limitation directed to enteric performance rather than merely coating composition.

A formulation can potentially avoid literal infringement by using:

• A coating that dissolves below pH 4.5.
• A coating that does not begin dissolving until above pH 5.5.
• A non-enteric delayed-release mechanism.
• A pH-independent release system.
• A coating that protects the composition through the stomach but dissolves through a different release mechanism.

The wording “begins to dissolve” may create testing disputes. Relevant evidence would include dissolution protocols, buffer composition, temperature, agitation, coating thickness, batch variability, and the definition of the initial dissolution event. The claim does not state a dissolution percentage, time point, or test method.

How do dependent claims narrow the patent?

Claims 2 through 6 narrow claim 1 by specifying dosage forms, coating chemistry, and route of administration.

Dosage forms

Claim 2 covers tablets and granules. Claim 3 narrows the granule embodiment to granules loaded into a capsule. A product marketed as a capsule may therefore fall within the claim if the capsule contains granules rather than a conventional powder, tablet, or liquid fill.

Claim 6 specifies oral administration. The claim structure leaves claim 1 broader in route terms, but the patent’s commercial application is an oral product.

Enteric-coating materials

Claim 4 lists a broad group of coating materials, including:

• Shellac.
• Cellulose acetate phthalate.
• Polyvinyl acetate phthalate.
• Hydroxypropyl methylcellulose phthalate.
• Hydroxypropyl methylcellulose acetate succinate.
• Carboxymethyl ethylcellulose.
• Methacrylic-acid-based polymers.
• Acrylic and methacrylic acid copolymers.
• Cellulose phthalate and trimellitate derivatives.

Claim 5 further specifies an enteric coating comprising a methacrylic acid ester. Methacrylic-acid-based coatings are commercially important because products such as Eudragit-type polymers can provide pH-dependent dissolution in the intestinal tract.

Claim 4 is not limited to one proprietary coating polymer. A generic manufacturer using a different listed polymer could still fall within the claim if all other limitations are met.

What are the method-of-use claims?

Claims 7 through 14 cover treatment methods rather than only the dosage form.

The primary method claim requires administering the claimed composition twice per day to a subject with nephropathic cystinosis. The dependent claims add dosing and biomarker limitations.

Limitation	Patent requirement
Disease	Nephropathic cystinosis
Administration frequency	Twice per day for claim 7
Per-administration dose	100 to 1,000 mg cysteamine free base
Biomarker target	White-blood-cell cystine below 1 nmol half-cystine/mg protein
Total daily dose	Approximately 1.35 g/m² cysteamine free base

These claims may be relevant even if a competing product has a different label or formulation. A product label that directs twice-daily treatment for nephropathic cystinosis could provide important evidence in a method-of-use case.

Claims 11 through 14 use “lowering the cystine content of cells” rather than the more specific “treating a subject” wording in claim 7. They may therefore present a separate infringement theory, subject to the precise construction of the patient, dosing, and biomarker limitations.

The supplied text states “white-blood-cell cysteine” in claim 13. The corresponding clinical biomarker for cystinosis is generally white-blood-cell cystine, expressed as half-cystine per milligram of protein. The apparent “cysteine” wording should be verified against the issued patent document before relying on claim 13 in litigation or freedom-to-operate work.

What is the patent’s priority and expiration position?

The patent issued on March 27, 2018. Its term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any disclaimer or correction affecting the term.

Public patent records associate the patent family with Raptor Pharmaceuticals and earlier cysteamine formulation filings. The family includes related patents directed to delayed-release cysteamine compositions and cystinosis treatment methods. The exact expiration date should be determined from the USPTO Patent Center record and any terminal-disclaimer documents because continuation practice can cause a later-issued patent to expire with an earlier family patent.

Event	Date or status
Patent issued	March 27, 2018
Patent number	U.S. 9,925,156
Original commercial context	Procysbi delayed-release cysteamine
Likely term basis	Earliest effective nonprovisional filing in the continuation family
Expected term	Approximately 20 years from the applicable nonprovisional priority date, adjusted by USPTO records
Patent-term extension	Must be verified against USPTO and FDA records
Current legal status	Verify in USPTO Patent Center before relying on the patent for enforcement or launch timing

A precise expiration date cannot be inferred solely from the issue date. For transaction, litigation, or launch analysis, the relevant record is the USPTO patent-term data together with any terminal disclaimer and patent-term adjustment certificate.

What is the Orange Book status of U.S. Patent 9,925,156?

The commercial product most closely associated with the patent is Procysbi delayed-release capsules and oral granules, which contain cysteamine bitartrate and are approved for nephropathic cystinosis.

Orange Book analysis must distinguish among:

1. Patents listed for the reference listed drug.
2. Patents that claim the drug substance.
3. Patents that claim the drug product or formulation.
4. Patents that claim an approved method of use.
5. Patents that are not listed, expired, delisted, or administratively removed.

A patent can be technically relevant to a marketed product without being an Orange Book-listed patent. Conversely, an Orange Book listing does not prove that every marketed product infringes every claim.

For Procysbi, the relevant FDA listing should be checked by application number and patent number. The listing can change through FDA administrative updates, patent expiration, delisting, or holder submissions. Patent 9,925,156 should not be treated as an Orange Book barrier without confirmation of its current listing status in the FDA database.

Which companies own or commercialize the relevant rights?

The patent family originated with Raptor Pharmaceuticals, which developed Procysbi. Horizon Therapeutics later acquired Raptor and its cysteamine franchise. Amgen acquired Horizon in 2023, making Amgen the ultimate corporate parent of the commercial rights associated with Horizon’s products, subject to the precise ownership and licensing chain for each patent and product.

Entity	Relevance
Raptor Pharmaceuticals	Original developer and early patent owner associated with Procysbi
Horizon Therapeutics	Later commercial owner of Procysbi and Raptor assets
Amgen	Acquired Horizon Therapeutics and became the parent company
Generic applicants	Potential ANDA filers, subject to Orange Book listings and Paragraph IV certifications
FDA	Regulates the approved product and Orange Book patent listings
USPTO	Maintains patent prosecution, assignment, term, and legal-status records

The patent assignment history should be reviewed separately from product commercialization. Patent ownership, FDA application ownership, and licensing rights can be held by different entities.

What Paragraph IV challenges or generic litigation affect Procysbi?

A Paragraph IV certification is relevant when an ANDA applicant asserts that an Orange Book-listed patent is invalid, unenforceable, or not infringed. The certification can trigger litigation under the Hatch-Waxman Act and may create a 30-month stay of FDA approval, subject to statutory conditions.

For U.S. Patent 9,925,156, the key questions are:

• Whether it is currently listed for Procysbi.
• Whether an ANDA applicant has certified against it.
• Whether the patent owner filed a timely infringement action.
• Whether any 30-month stay has expired, been shortened, or been terminated.
• Whether a settlement limits launch timing.
• Whether the patent was disclaimed, invalidated, or removed from the listing.

No Paragraph IV case or settlement should be attributed to this patent without matching the patent number to a complaint, FDA litigation listing, or court docket. A generic dispute involving another Procysbi patent does not automatically apply to Patent 9,925,156.

How strong is the patent estate for cysteamine products?

The estate is stronger when evaluated as a family rather than through Patent 9,925,156 alone. A competitor may need to address several layers:

Patent layer	Potential protection
Composition	Cysteamine bitartrate, cystamine, binders, and enteric coating
Release profile	pH-triggered dissolution and delayed release
Dosage form	Capsules, tablets, and granules
Treatment method	Twice-daily cystinosis treatment
Dose	100 to 1,000 mg per administration and approximately 1.35 g/m²/day
Biomarker	White-blood-cell cystine target
Manufacturing	Granulation, coating, and processing conditions
Product-specific claims	Formulation and approved dosage forms listed for the reference product

The principal weakness is claim specificity. A product that omits cystamine, uses a substantially different release mechanism, or employs a dosing schedule outside the claimed regimen may reduce exposure to this patent. The principal strength is the combination of structural and functional limitations. A competing product may need to avoid several elements simultaneously to achieve a clean design around.

What generic launch risks exist?

A generic cysteamine entrant faces several possible launch scenarios.

Scenario 1: No Orange Book patent challenge

If no relevant patent is listed, FDA approval may proceed after satisfaction of the applicable regulatory requirements. Separate non-Orange-Book patents could still create litigation risk, particularly for formulation or manufacturing claims.

Scenario 2: Paragraph IV certification

A Paragraph IV filing can prompt patent litigation and a potential 30-month approval stay. The launch date would depend on litigation outcome, settlement terms, court judgment, exclusivity, and the patent’s actual expiration.

Scenario 3: Section VIII carve-out

If the relevant patent claims an approved method of use rather than the product itself, an ANDA applicant may attempt a Section VIII statement and omit the patented indication from its labeling. This strategy is less useful when the patent claims the composition itself.

Scenario 4: At-risk launch

A generic applicant may launch before final resolution of patent litigation. That creates potential damages, injunction, and market disruption exposure if the patent is later upheld and found infringed.

How can a competitor design around Patent 9,925,156?

Potential design-around paths include:

• Removing cystamine from the core.
• Using cysteamine hydrochloride or another cysteamine salt without cysteamine bitartrate.
• Replacing the enteric coating with a non-pH-dependent delayed-release system.
• Selecting a coating that begins dissolution outside the pH 4.5 to 5.5 range.
• Using a non-enteric dosage form with a different delivery mechanism.
• Changing the dosing schedule where clinically and regulatorily acceptable.
• Avoiding the claimed cystine biomarker target in labeling, while recognizing that actual use may still matter.
• Using a formulation that does not contain the listed coating materials.

A design around must account for other patents in the family. Avoiding claim 1 does not eliminate risk under separate formulation, manufacturing, or method patents.

How does Patent 9,925,156 compare with conventional cysteamine therapy?

Procysbi was developed to address the administration burden associated with immediate-release cysteamine. Immediate-release cysteamine products generally require more frequent administration and are associated with gastrointestinal and odor-related tolerability issues. Patent 9,925,156 focuses on an enteric, delayed-release composition administered twice daily.

Attribute	Immediate-release cysteamine	Procysbi-type delayed-release product
Release	Immediate or conventional release	Enteric and delayed release
Typical administration burden	More frequent dosing	Twice-daily regimen
Patent relevance	May fall outside this patent’s composition claims	Closely aligned with the claimed subject matter
Key technical issue	Maintaining cysteamine exposure	Protecting the core and controlling intestinal release
Main regulatory pathway	Approved cysteamine therapy	Approved delayed-release cysteamine therapy

The patent does not cover the entire cysteamine therapeutic class. Its value is concentrated in the formulation and regimen associated with delayed-release oral treatment.

What patent litigation and regulatory records should be reviewed?

A complete freedom-to-operate review should reconcile the following records:

1. USPTO Patent Center for Patent 9,925,156.
2. USPTO assignment and terminal-disclaimer records.
3. FDA Orange Book listings for the Procysbi application.
4. FDA Drugs@FDA approval history and labeling.
5. PACER and district-court dockets for patent litigation.
6. PTAB records for inter partes review or post-grant proceedings.
7. Patent-family records for related U.S. continuations and foreign counterparts.
8. FDA ANDA litigation listings for any cysteamine generic applicant.

The key technical evidence would include the competitor’s full qualitative and quantitative formulation, coating polymer, dissolution profile, granulation process, label, and dosing instructions.

Key Takeaways

• U.S. Patent 9,925,156 primarily protects enterically coated cysteamine compositions containing cysteamine bitartrate and cystamine or a cystamine salt.
• The pH 4.5 to 5.5 dissolution limitation is central to claim 1.
• Claims 2 through 6 cover tablets, granules, capsules, listed enteric polymers, methacrylic-acid-based coatings, and oral use.
• Claims 7 through 14 cover twice-daily treatment, dosing, cystine biomarker control, and total daily dose.
• The patent is closely associated with the Procysbi delayed-release cysteamine franchise.
• The patent’s precise expiration date requires confirmation of the earliest effective filing date, terminal disclaimers, patent-term adjustment, and any patent-term extension.
• Orange Book listing status must be checked directly because technical relevance does not establish current listing.
• A clean design around may require avoiding cystamine, the specified pH release window, the claimed enteric polymers, or the twice-daily cystinosis regimen.
• Related patents may present separate formulation, manufacturing, method-of-use, or product-label risks.

Frequently Asked Questions

Does U.S. Patent 9,925,156 cover cysteamine hydrochloride?

Not necessarily. Claim 1 specifically requires cysteamine bitartrate and cystamine or a pharmaceutically acceptable cystamine salt. A product using only cysteamine hydrochloride would need to be assessed against the claim language and related patents separately.

Does a capsule automatically infringe Patent 9,925,156?

No. Claim 3 is directed to granules loaded into a capsule and depends on the limitations of claims 1 and 2. A capsule with a different fill material, coating, active ingredient combination, or release mechanism may not meet the claim.

Can a generic company avoid the patent by using a different enteric polymer?

Possibly, but not automatically. Claim 1 is not limited to the polymers listed in claim 4. A different polymer could still infringe claim 1 if it produces the required pH-dependent dissolution and the formulation contains the required core components.

Is the 1.35 g/m² dose required for every infringement case?

No. The dose appears in dependent claims 10 and 14. Claims 7 and 11 are broader in dose terms, although claims 8 and 12 add a 100 to 1,000 mg per-administration range.

Does Patent 9,925,156 block all cystinosis treatments?

No. The patent is limited to the claimed composition and treatment elements. Immediate-release cysteamine, different cysteamine salts, non-enteric formulations, and unrelated cystinosis treatments require separate analysis.

References

1. U.S. Patent No. 9,925,156. (2018). Enterically coated cysteamine compositions and methods of use. United States Patent and Trademark Office. https://patents.google.com/patent/US9925156B2/en

2. U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/

3. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/

4. U.S. Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/

5. U.S. Food and Drug Administration. (2013). Procysbi prescribing information. Horizon Therapeutics. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203389s000lbl.pdf

6. U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension information. https://www.uspto.gov/patents/laws/patent-term-calculator

Drugs Protected by US Patent 9,925,156

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	9,925,156*PED				Y
Horizon	PROCYSBI	cysteamine bitartrate	CAPSULE, DELAYED RELEASE;ORAL	203389-002	Apr 30, 2013		RX	Yes	Yes	9,925,156*PED				Y
Horizon	PROCYSBI	cysteamine bitartrate	GRANULE, DELAYED RELEASE;ORAL	213491-001	Feb 14, 2020		RX	Yes	No	9,925,156*PED				Y
Horizon	PROCYSBI	cysteamine bitartrate	GRANULE, DELAYED RELEASE;ORAL	213491-002	Feb 14, 2020		RX	Yes	Yes	9,925,156*PED				Y

International Family Members for US Patent 9,925,156

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1919458		C300649	Netherlands
European Patent Office	1919458		CR 2014 00013	Denmark
European Patent Office	1919458		194 50001-2014	Slovakia
European Patent Office	1919458		19/2014	Austria
European Patent Office	1919458		300649	Netherlands