US Patent 10,493,051: Claim Scope, Exclusivity, Orange Book Status, and Generic Entry Risk

US Patent 10,493,051 protects low-aluminum, stable cysteine hydrochloride solutions intended for neonatal and infant total parenteral nutrition, with additional coverage for patients with severe liver disease. The patent’s commercial relevance is concentrated in the 50 mg/mL cysteine hydrochloride injection product Elcys, marketed by Exela Pharma Sciences.

The patent is composition-focused. Its strongest claim elements are the combination of:

Approximately 50 mg/mL cysteine or cysteine hydrochloride;
Acidic pH of approximately 1.0 to 2.5;
Aluminum below specified thresholds;
Low dissolved oxygen;
Low cystine content and absence of cystine precipitation;
Suitability for parenteral nutrition in neonates, infants, or patients with severe liver disease.

The patent does not broadly claim every cysteine injection, every total parenteral nutrition formulation, or a manufacturing process for cysteine hydrochloride.

What does US Patent 10,493,051 cover?

US Patent 10,493,051 covers pharmaceutical cysteine solutions with controlled chemical and particulate impurities. The independent claims divide the estate into three principal claim groups.

Claim group	Independent claim	Principal subject matter
Low-aluminum cysteine solution	1	Approximately 50 mg/mL cysteine, pH 1.0-2.5, aluminum below 400 μg/L, use as a neonatal or infant TPN additive
High-purity, low-oxygen cysteine solution	21	At least 99% cysteine, less than 1% cystine, dissolved oxygen below 2 mg/L, pH 1.0-1.5, approximately 50 mg/mL cysteine hydrochloride
Defined neonatal or infant product	26	50 mg/mL cysteine hydrochloride monohydrate in water, pH 1.0-2.5, aluminum below 145 μg/L
Defined severe-liver-disease product	27	The same formulation designed for parenteral nutrition in patients with severe liver disease and impaired cysteine conversion

The claims target product attributes rather than a particular brand name, container, or manufacturing sequence.

Which patent claims are most commercially important?

Claim 1: broadest practical composition claim

Claim 1 requires all of the following:

A solution of cysteine;
A pharmaceutically acceptable solvent;
Approximately 50 mg/mL cysteine;
Less than approximately 400 μg/L aluminum;
pH of approximately 1.0 to 2.5;
Suitability as a TPN additive for a neonate or infant.

The claim is broad relative to the dependent claims because it permits aluminum concentrations up to, but not reaching, approximately 400 μg/L and does not require low dissolved oxygen, a specified cystine concentration, water, cysteine hydrochloride monohydrate, or a silica-lined vial.

A competing product satisfying each limitation could fall within claim 1 even if it uses a different supplier, container, sterilization process, or excipient.

Claims 2-6: aluminum concentration hierarchy

Claims 2 through 6 progressively narrow the aluminum limitation.

Claim	Aluminum limitation
1	Less than approximately 400 μg/L
2	Less than approximately 145 μg/L
3	Less than approximately 100 μg/L
4	Less than approximately 30 μg/L
5	Less than approximately 10 μg/L
6	Approximately 1 to 145 μg/L

Claims 5 and 6 create different boundaries. Claim 5 requires less than approximately 10 μg/L. Claim 6 requires a positive range beginning at approximately 1 μg/L and extending to approximately 145 μg/L. A formulation with aluminum below 1 μg/L could satisfy claim 5 but may not satisfy claim 6, depending on how the range terms are construed and measured.

The aluminum limitations are likely to be central in a generic challenge because aluminum concentration is measurable through release testing. The patent holder would likely rely on batch records, certificates of analysis, stability data, and inductively coupled plasma testing to establish infringement.

Claims 7-11: pH, oxygen, and particulate controls

Claims 7 and 8 narrow the pH range:

Claim 7: pH approximately 1.0 to 1.5;
Claim 8: pH approximately 1.0 to 1.3.

Claim 9 adds dissolved oxygen below 2 mg/L. Claims 10 and 11 add the absence of visible particulate matter or precipitated cystine.

These limitations address cysteine oxidation and degradation. Cysteine can oxidize to cystine, and cystine precipitation can create visible particles in an injectable product. The claims therefore combine chemical purity with injectable-product quality attributes.

Claim 10 concerns visible particulate matter generally. Claim 11 is narrower because it targets precipitated cystine specifically. A product could be free of visible particles but still contain dissolved or subvisible cystine, while a product could contain no cystine precipitate but still have another form of particulate matter.

Claims 12-14: solvent and salt form

Claim 12 specifies water as the solvent. Claim 13 specifies cysteine hydrochloride. Claim 14 narrows the salt to cysteine hydrochloride monohydrate.

These claims are commercially important because a 50 mg/mL cysteine hydrochloride monohydrate solution in water is the formulation profile associated with Elcys. A generic using an anhydrous salt, a different solvent system, or a materially different cysteine form could seek to avoid these limitations, although it could remain exposed to broader claims if the product still satisfies their elements.

Claims 15-18: stability and container conditions

Claims 15 and 16 require the aluminum limitation to remain satisfied after storage:

18 months at 25°C and 60% relative humidity in a silica-lined vial;
6 months at 40°C and 75% relative humidity in a silica-lined vial.

Claims 17 and 18 similarly require the absence of visible particulate matter after those storage conditions.

These claims are not limited merely to an initial release specification. They address stability performance under defined conditions. Their value depends on whether the accused product is tested or sold in a silica-lined vial and whether the claim’s storage language is treated as a product limitation or as a test-defined characteristic.

A generic using a different container, such as a polymer vial or a non-silica-coated glass vial, may reduce exposure to claims 15-18. That design choice would not necessarily avoid claims 1, 21, 26, or 27.

How do claims 21-27 differ from claims 1-20?

Claims 21-27 provide alternative infringement routes based on cysteine purity and intended clinical use.

Claim 21: high-purity, low-oxygen formulation

Claim 21 requires:

At least 99% cysteine by weight;
Less than 1% cystine by weight;
Dissolved oxygen below approximately 2 mg/L;
pH approximately 1.0 to 1.5;
Approximately 50 mg/mL cysteine hydrochloride.

This claim is less dependent on the aluminum limitation. A product could potentially avoid claims 1 and 26 by exceeding their aluminum thresholds while still infringing claim 21 if it meets the purity, oxygen, pH, and concentration limitations.

Claim 22 narrows cystine content below approximately 0.5%. Claims 23-25 add absence of precipitated cystine and aluminum thresholds below approximately 400 μg/L and 145 μg/L.

Claim 26: neonatal and infant TPN formulation

Claim 26 is directed to a defined product:

50 mg/mL cysteine hydrochloride monohydrate;
Water;
pH approximately 1.0 to 2.5;
Aluminum below approximately 145 μg/L;
Designed for parenteral administration as part of TPN to a neonate or infant.

This is the claim most closely aligned with the commercial neonatal-use profile of Elcys. It is narrower than claim 1 because it requires water, cysteine hydrochloride monohydrate, and the 145 μg/L aluminum limit. It is potentially stronger commercially because it maps closely onto the labeled product configuration.

Claim 27: severe liver disease formulation

Claim 27 covers the same basic formulation but directs it to patients with severe liver disease who have impaired enzymatic conversion of cysteine.

The claim creates a separate use-specific enforcement path. A product labeled only for neonatal or infant TPN may present a different risk profile from a product labeled for both neonatal nutrition and patients with severe liver disease. A generic applicant’s proposed labeling would therefore matter, although an identical formulation may still present composition-claim exposure independent of its label.

What patent protects Elcys and when does exclusivity expire?

The principal identified patent is US 10,493,051, issued December 3, 2019, with Exela Pharma Sciences associated with the commercial product and patent rights. The patent has an April 2035 patent-term endpoint based on its 2015 nonprovisional filing date and the 20-year patent term framework.[1]

Milestone	Date or status
US patent application filing	April 2015
US Patent 10,493,051 issued	December 3, 2019
Patent-term endpoint	Approximately April 2035
Elcys FDA approval	2019
Primary product	Cysteine hydrochloride injection, 50 mg/mL
FDA pathway	NDA 209661
Dosage form	Sterile injectable solution
Primary use	Additive to TPN, particularly neonatal and infant nutrition

The precise patent expiration date should be determined from the USPTO patent-term adjustment calculation and the Orange Book listing. Patent expiry and FDA regulatory exclusivity are separate rights. A patent may remain enforceable after FDA exclusivity ends, and FDA approval does not itself establish patent infringement.

What is the Orange Book status of US 10,493,051?

US 10,493,051 is associated with the Elcys cysteine hydrochloride injection product and is listed as a drug-related patent in FDA patent records for the product.[2] The listing gives the patent holder a mechanism to notify an abbreviated new drug application applicant of a patent certification and to pursue a patent infringement action following a Paragraph IV notice.

The Orange Book listing does not mean that the patent covers every cysteine hydrochloride product. It means the patent holder has identified the patent as claiming the approved drug or an approved method of using it under FDA listing rules.

The key Orange Book implications are:

An ANDA applicant must address the listed patent through Paragraph I, II, III, or IV certification.
A Paragraph IV certification can trigger patent litigation.
A timely infringement action can create a 30-month stay of FDA approval under the Hatch-Waxman framework.
The stay does not automatically prevent all commercial activity after patent expiry or a successful litigation outcome.
The listing does not resolve claim construction, validity, or infringement.

Are there Paragraph IV challenges or generic litigation?

A Paragraph IV challenge must be assessed from current FDA Orange Book records, ANDA litigation filings, and district-court dockets. The patent’s commercial risk is highest if an ANDA applicant asserts that:

The proposed product does not satisfy the aluminum threshold;
The product uses a different salt or solvent;
The product has a different pH or dissolved oxygen profile;
The proposed label omits neonatal, infant, or severe-liver-disease use;
The patent claims are invalid for anticipation or obviousness;
The claims are indefinite because of terms such as “about,” “suitable,” “designed to be,” or “devoid of visible particulate matter.”

The principal litigation issues would likely be:

Issue	Relevance
“About 50 mg/mL”	Determines the permitted concentration range
“About” aluminum thresholds	Determines whether measurement variability affects infringement
“Suitable for use”	May be treated as a functional limitation or intended-use language
“Designed to be parenterally administered”	May depend on formulation capability, labeling, and intended use
“Devoid of visible particulate matter”	Requires a defined inspection method and acceptance standard
Stability limitations	Raises questions about whether storage conditions are product limitations
Cystine content	Requires validated assay methodology and sampling controls

No method-of-use claim is needed to create substantial exposure if the product composition itself meets claims 1, 21, or 26.

How strong is the patent estate?

The patent estate is moderately strong against a product that copies the commercial formulation, but narrower against materially different formulations.

Strengths

Claims multiple independent formulation profiles.
Uses measurable chemical specifications.
Covers aluminum, cystine, oxygen, pH, and particulate attributes.
Includes both neonatal and severe-liver-disease applications.
Claims the clinically relevant 50 mg/mL concentration.
Includes stability-related dependent claims.
Aligns closely with the approved product profile.

Weaknesses and design-around opportunities

No express manufacturing-process claims appear in the provided claims.
No claim broadly covers the complete TPN admixture.
A formulation using a different salt or solvent may avoid claims 12-14 and 26.
A product with aluminum above the specified thresholds may avoid claims 1 and 26.
A product outside the claimed pH or concentration ranges may avoid multiple claims.
A different container may avoid the silica-vial stability claims.
“About,” “suitable,” and “designed to be” may create construction disputes.
The claims are vulnerable if prior art disclosed the same concentration, pH, aluminum control, and cysteine stability characteristics.

The claims are strongest when the accused product has the same formulation and is labeled for the same patient populations. They are weaker against a genuinely different low-aluminum cysteine product that remains outside the concentration, pH, oxygen, cystine, and intended-use combinations.

What formulation patents protect cysteine injection products?

The central protected formulation attributes are:

Attribute	Claimed range or requirement
Cysteine concentration	Approximately 50 mg/mL
Salt	Cysteine hydrochloride, including monohydrate
Solvent	Pharmaceutically acceptable solvent; water in narrower claims
pH	Approximately 1.0-2.5, with narrower ranges to 1.0-1.3
Aluminum	Less than approximately 400, 145, 100, 30, or 10 μg/L
Cystine	Less than 1%, with narrower claim below 0.5%
Dissolved oxygen	Less than approximately 2 mg/L
Particulates	No visible particulate matter
Cystine precipitation	No precipitated cystine
Container stability	Silica-lined vial under defined storage conditions
Clinical setting	Neonatal or infant TPN; severe liver disease

The patent is therefore a quality-by-design patent around injectable cysteine stability rather than a basic composition-of-matter patent on cysteine itself.

Does biosimilar risk apply?

No. Cysteine hydrochloride is a small-molecule active pharmaceutical ingredient, not a biologic. The relevant competitive pathway is an ANDA for a generic drug, not a biosimilar application under section 351(k) of the Public Health Service Act.

The principal regulatory and commercial barriers are:

Pharmaceutical equivalence;
Sterility and injectable-product controls;
Aluminum and elemental impurity testing;
Stability data;
Container-closure compatibility;
Labeling and intended-use limitations;
Orange Book patent certifications;
Potential Hatch-Waxman litigation.

What generic launch scenarios exist?

Scenario 1: Paragraph III certification

A generic applicant accepts the patent and delays launch until patent expiry. On the assumed April 2035 patent endpoint, this produces the lowest litigation risk but postpones market entry.

Scenario 2: Paragraph IV challenge

The applicant alleges noninfringement, invalidity, or unenforceability. The principal arguments would likely focus on prior-art disclosure of low-aluminum cysteine solutions, obviousness of controlling oxygen and cystine, and construction of “about” and intended-use limitations.

Scenario 3: Formulation design-around

A generic could use a different combination of:

Cysteine concentration;
pH;
Salt form;
Solvent;
Aluminum specification;
Container system;
Oxygen-control strategy.

The design-around must be evaluated against all independent claims, not only claim 26.

Scenario 4: Label-limited approval

A product could seek approval with a narrower indication that omits one or more claimed populations. This may reduce method-related exposure but would not avoid composition claims if the product itself satisfies the claimed formulation limitations.

What commercial exposure does the patent create?

Elcys is a specialized injectable product used in hospital nutrition, especially neonatal and pediatric settings. Its market is narrower than that of mass-market generic drugs, but supply reliability and formulation compliance can support meaningful pricing and contracting value.

The patent creates commercial exposure for a competing product that copies the approved formulation because:

The product is a sterile injectable;
Formulation deviations can affect safety and stability;
Aluminum and particulate specifications are directly tied to product release;
Neonatal use creates a high regulatory burden;
A generic may need to reproduce the same low-impurity performance to obtain acceptance.

No reliable public revenue figure is established by the cited patent and FDA materials. The value of the patent is better measured by the timing of generic entry, hospital supply access, and the cost of developing a non-infringing formulation than by an isolated sales estimate.

Key Takeaways

US 10,493,051 is a formulation patent covering stabilized cysteine hydrochloride solutions.
The core commercial profile is approximately 50 mg/mL cysteine hydrochloride at acidic pH with controlled aluminum.
Claims 1, 21, 26, and 27 are the principal independent claim groups.
Claims 26 and 27 closely track neonatal/infant TPN and severe-liver-disease use.
The patent does not broadly claim all cysteine injections or all TPN formulations.
Low aluminum, low oxygen, low cystine, and particulate control are the main technical barriers.
The patent is associated with Elcys and has an expected term extending to approximately April 2035, subject to the official patent-term calculation.
Generic applicants face ANDA patent-certification and Paragraph IV litigation risk.
Biosimilar rules do not apply because cysteine hydrochloride is a small molecule.
A successful design-around would need to avoid the full combination of concentration, pH, impurity, oxygen, salt, solvent, and intended-use limitations.

FAQs

Is US 10,493,051 a composition-of-matter patent?

No. It is a formulation patent. It protects defined cysteine solutions with specified concentration, pH, aluminum, cystine, oxygen, particulate, stability, and intended-use characteristics.

Does the patent cover the entire TPN formulation?

The provided claims cover a cysteine solution used as a TPN additive. They do not expressly claim every amino-acid, glucose, lipid, electrolyte, or complete TPN admixture.

Can a generic avoid the patent by changing the vial?

Changing from a silica-lined vial may avoid claims 15-18, but it does not necessarily avoid claims 1, 21, 26, or 27.

Can a generic avoid infringement by using cysteine hydrochloride anhydrous instead of monohydrate?

That change may avoid claims requiring cysteine hydrochloride monohydrate, especially claim 26. It would not automatically avoid broader claims that do not require the monohydrate form.

Is aluminum contamination the main generic-development issue?

It is one of the principal issues. The patent includes multiple aluminum thresholds, and the applicant would need validated testing and stability data to determine whether its product falls within the claimed ranges.

References

United States Patent and Trademark Office. (2019). Cysteine solutions and methods of use thereof, U.S. Patent No. 10,493,051.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2019). Elcys (cysteine hydrochloride injection) prescribing information. Exela Pharma Sciences, LLC.
U.S. Food and Drug Administration. (2017). FDA’s Orange Book: Questions and answers.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation resources.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Baxter Hlthcare Corp	NOURESS	cysteine hydrochloride	SOLUTION;INTRAVENOUS	212535-001	Dec 13, 2019		DISCN	Yes	No	⤷ Start Trial	⤷ 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

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3070798	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,493,051

Which drugs does patent 10,493,051 protect, and when does it expire?

Summary for Patent: 10,493,051