US Patent 10,653,719: L-Cysteine Parenteral Nutrition Solution Claims, Scope, and Patent Landscape

US Patent No. 10,653,719 protects defined L-cysteine solutions for parenteral nutrition, particularly neonatal and infant formulations. The core combination is approximately 50 mg/mL L-cysteine hydrochloride monohydrate, low aluminum, acidic pH, and control of visible particles or cystine precipitation. Several dependent claims add low dissolved oxygen and stability periods extending to 24 months.

The patent is directed to formulation quality and stability rather than to L-cysteine itself. A competing product may avoid literal infringement by changing one or more measurable attributes, but the claim language creates a substantial formulation-screening burden because claims 1, 12, and 17 cover overlapping solution platforms.

What does US Patent 10,653,719 claim?

The patent contains three independent formulation claims:

Independent claim	Principal covered formulation	Patient/use limitation	Additional requirement
Claim 1	Approximately 50 mg/mL L-cysteine hydrochloride monohydrate, less than approximately 150 ppb aluminum, pH 1.0-2.5	Suitable as a parenteral nutrition additive	Substantially free of visually detectable particulate matter
Claim 12	Same basic formulation and aluminum/pH limits	Suitable for administration to a neonate or infant	Particle-free for at least six months after manufacture
Claim 17	Same basic formulation and aluminum/pH limits	Suitable for administration to a neonate or infant	Prepared or maintained in a low-oxygen environment and substantially free of visually detectable particles

All three claims use "comprising." That transition generally permits additional ingredients or process features unless the added components defeat another express limitation. A formulation containing buffers, water for injection, nitrogen headspace, or other excipients may still fall within the claims if it satisfies the recited concentration, pH, aluminum, particle, and intended-use requirements.

How broad is the core claim scope?

Claim 1 is the broadest independent claim because it does not require a specified shelf-life period, neonatal or infant administration, or expressly recite a low-oxygen environment.

Its required elements are cumulative:

A solution of L-cysteine.
A pharmaceutically acceptable carrier.
Approximately 50 mg/mL L-cysteine hydrochloride monohydrate, or an equivalent amount of another pharmaceutically acceptable L-cysteine form.
Less than approximately 150 ppb aluminum.
A pH of approximately 1.0 to 2.5.
Substantial freedom from visually detectable particulate matter.
Suitability for use as a parenteral nutrition additive.

A product that lacks any one required element may avoid literal infringement of claim 1. The practical difficulty is that several elements are formulation attributes rather than label statements. Aluminum concentration, dissolved oxygen, cystine precipitation, particle status, and pH may need to be established through batch records, release testing, stability data, or expert analysis.

What does "about 50 mg/mL" mean?

"About 50 mg/mL" introduces a numerical boundary issue. The claims do not define the permitted deviation. A court would likely evaluate the specification, prosecution history, analytical precision, formulation practice, and whether the accused concentration performs substantially the same function in substantially the same way.

The alternative wording covering an "equivalent amount" of a pharmaceutically acceptable L-cysteine, salt, or hydrate broadens the claim beyond the named monohydrate. A formulation using anhydrous L-cysteine, another salt, or a different hydrate could remain within the claim if it supplies the equivalent L-cysteine amount.

What do the aluminum limitations protect?

The aluminum limitations form a descending concentration ladder:

Claim	Aluminum limitation
Claim 1	Less than approximately 150 ppb
Claim 2	Less than approximately 100 ppb
Claim 3	Less than approximately 50 ppb
Claim 4	Less than approximately 20 ppb
Claim 5	Less than approximately 10 ppb
Claim 6	Approximately 1 to approximately 150 ppb

Claims 2 through 5 narrow claim 1 by imposing progressively lower maximum aluminum concentrations. Claim 6 is different. It requires a lower bound of approximately 1 ppb while retaining the approximately 150 ppb upper limit.

A formulation containing no detectable aluminum could fall within claims 1 through 5, assuming the other requirements are met. It may not fall within claim 6 if the claim is construed to require at least approximately 1 ppb.

Aluminum control is commercially relevant for parenteral nutrition products because aluminum exposure is a recognized FDA concern, particularly for premature neonates and patients receiving prolonged parenteral nutrition. FDA regulations address aluminum in large-volume parenteral products, small-volume parenteral products, and pharmacy bulk packages. The patent claims, however, use substantially lower ppb thresholds than the general regulatory framework in many circumstances. [1]

What do the pH and cystine limitations cover?

The independent claims require a pH from approximately 1.0 to approximately 2.5. Claim 8 narrows this to a pH of approximately 1.8 and requires the solution to be substantially free of cystine precipitates.

Claims 11, 16, 26, and 27 separately require the solution to be essentially free of cystine precipitates. These claims create an important distinction:

"Visually detectable particulate matter" concerns observable particles generally.
"Cystine precipitates" identifies a particular chemical or physical failure mode.
A solution could theoretically be free of detectable particles but still require proof that cystine precipitates are absent or essentially absent.
The claims do not state a numerical cystine limit.

At low pH, L-cysteine is maintained in an acidic solution, but oxidation can produce cystine. Cystine formation can result in visible precipitation or particulate matter over time. The claims therefore combine chemical composition with physical stability.

What do the dissolved-oxygen claims protect?

Claim 7 depends from claim 1 and requires dissolved oxygen below approximately 2 ppm. Claims 22 through 25 depend from claim 17 and create a broader set of oxygen limitations:

Claim	Dissolved oxygen limitation
Claim 7	Less than approximately 2 ppm
Claim 22	Less than approximately 5 ppm
Claim 23	Less than approximately 2 ppm
Claim 24	Less than approximately 1 ppm
Claim 25	Approximately 0.4 to approximately 3.8 ppm

Claims 22 and 23 overlap substantially. Claim 24 is narrower. Claim 25 is a range claim and may cover some formulations that do not meet claim 24.

"Low oxygen environment" in claim 17 is not numerically defined in the independent claim. Claim 22 supplies one quantitative route for satisfying a dependent claim, but claim 17 itself could raise claim-construction issues concerning the oxygen level, container headspace, manufacturing atmosphere, dissolved oxygen at release, or a combination of those factors.

A generic or competing manufacturer would need to test dissolved oxygen at a defined point in the manufacturing and stability process. Oxygen values can vary with container closure, temperature, agitation, sampling method, and measurement technology.

What stability periods are protected?

Claims 9 and 12 through 15 address stability periods.

Claim	Stability requirement
Claim 9	No visually detectable particulate matter after 18 months at approximately 25°C and 60% relative humidity
Claim 12	No visually detectable particulate matter for at least six months from manufacture
Claim 13	At least nine months
Claim 14	At least 12 months
Claim 15	At least 24 months
Claims 18-21	Six, nine, 12, or 24 months, combined with claim 17's low-oxygen formulation

Claims 12 through 15 and 17 through 21 are directed to commercial shelf-life characteristics. They can be particularly relevant to a product with a long labeled shelf life, although patent infringement generally turns on whether the product meets the claim limitations, not solely on the approved expiration date.

Claim 9 is narrower than claims 12 and 17 because it specifies approximately 25°C and 60% relative humidity and requires an aqueous carrier through claim 10. Claims 12 through 15 do not expressly require those storage conditions.

Which claims are most important commercially?

Claims 1, 12, and 17 are the principal blocking claims.

Claim 1: broad formulation coverage

Claim 1 is the principal risk for a standard 50 mg/mL cysteine hydrochloride parenteral nutrition additive. It does not require a neonatal indication or a stated shelf-life period.

Claim 12: neonatal and infant products

Claim 12 targets products positioned for neonates or infants and adds a minimum six-month particle-free period. Claims 13 through 15 increase the stability period to nine, 12, and 24 months.

Claim 17: low-oxygen neonatal formulations

Claim 17 combines neonatal or infant use with low-oxygen processing or storage. Claims 18 through 21 add the same four stability periods found in claims 12 through 15.

The patent has claim redundancy. If a court invalidated or narrowed one independent claim, overlapping claims could preserve coverage for a product that meets additional shelf-life or oxygen limitations.

What design-around options exist?

A design-around analysis should focus on measurable formulation parameters rather than the product name.

Design-around variable	Potential effect
L-cysteine concentration materially outside the "about 50 mg/mL" range	May avoid the concentration limitation, subject to construction of "about"
pH above approximately 2.5 or below approximately 1.0	May avoid the pH limitation, though stability and tolerability must be assessed
Aluminum at or above the claimed threshold	May avoid the low-aluminum limitation but creates regulatory and quality concerns
Product not suitable as a parenteral nutrition additive	Could avoid the intended-use limitation
Product labeled only for a non-neonatal use	May be relevant to claims 12 and 17, but would not necessarily avoid claim 1
Higher dissolved oxygen	May avoid claims 7 and 22-25, but not necessarily claims 1 or 12
Demonstrable cystine precipitation or visible particles	Could avoid the particle-free limitations, but would create an unacceptable injectable-product quality profile
Shorter validated shelf life	May avoid duration-specific claims while leaving claim 1 exposed
Non-equivalent L-cysteine form or concentration	May avoid the equivalent-amount limitation depending on formulation and claim construction

The most difficult design-around is likely a commercially viable 50 mg/mL acidic L-cysteine solution that remains stable, low in aluminum, and free of visible particles. Changing oxygen conditions alone does not address claims 1 and 12.

Does the patent cover manufacturing methods?

The supplied claims are product and product-property claims. They do not expressly claim:

Nitrogen sparging;
Vacuum deaeration;
A nitrogen or argon headspace;
Specific container-closure systems;
A sterilization cycle;
A mixing sequence;
Raw-material qualification;
Aluminum-free processing equipment;
A specific filling process;
A particular cysteine synthesis or purification method.

A manufacturing process can still be relevant as evidence that the resulting solution meets the claimed properties. A process using low-aluminum contact materials and oxygen-controlled filling may produce a formulation within the claims even though the process itself is not claimed.

The patent does not, based on the supplied claims, block all L-cysteine manufacturing. Its barrier is concentrated in the finished injectable solution and its quality attributes.

What is the Orange Book status?

The supplied claim text does not establish whether US Patent 10,653,719 is listed in the FDA Orange Book for a particular L-cysteine hydrochloride injection NDA. Orange Book listing is product-specific and depends on the NDA holder's submission and FDA acceptance of the patent information. A patent may be relevant to a product without appearing in the Orange Book, particularly where the patent is not considered to claim the approved drug substance, drug product, or approved method of use under the applicable listing rules. [2]

For an ANDA strategy, the relevant questions are:

Whether the reference drug is an NDA-listed L-cysteine hydrochloride injection.
Whether the patent appears in the Orange Book for that reference product.
Whether the patent expiration date has passed.
Whether the ANDA must include a Paragraph III certification, Paragraph IV certification, or another certification.
Whether the NDA holder files a timely infringement action after receiving a Paragraph IV notice.

A Paragraph IV challenge to a listed patent can trigger a 30-month stay of approval if the statutory conditions are met. [3]

Are there biosimilar risks?

There is no biosimilar pathway issue for L-cysteine hydrochloride injection. L-cysteine is a small-molecule active ingredient, and a competing injectable would generally proceed through an ANDA or, depending on product differences, a 505(b)(2) application rather than a biosimilar application under section 351(k) of the Public Health Service Act.

The relevant competitive risks are generic or follow-on injectable entry, not biosimilar substitution.

When does US Patent 10,653,719 expire?

The patent issued on May 19, 2020. Patent term is generally 20 years from the earliest effective US nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable priority relationship. The issue date alone does not establish the expiration date. [4]

An exact expiration date requires the patent's application-data record, earliest effective nonprovisional filing date, patent-term adjustment, and any terminal disclaimer. The supplied claims do not contain those data. The patent should not be treated as expiring 20 years after issuance.

Maintenance-fee status also matters. A utility patent can lapse for failure to pay maintenance fees at the 3.5-, 7.5-, or 11.5-year stages, subject to statutory grace periods and reinstatement rules. [5]

What litigation and Paragraph IV activity affect the patent?

The claim text alone does not establish a filed infringement case, ANDA challenge, settlement, or licensed entry date. Patent litigation must be checked against the patent number, assignee, NDA product, and defendant. Relevant sources include PACER, the Federal Court system, USPTO Patent Center, and FDA Orange Book records.

A litigation review should identify:

Any suit filed within 45 days after a Paragraph IV notice;
Whether a 30-month stay was triggered;
Claim construction rulings;
Invalidity arguments under sections 101, 102, 103, and 112;
Written-description and enablement challenges;
Prosecution-history estoppel;
Settlement restrictions and agreed generic launch dates;
Any covenant not to sue or license.

The most credible invalidity pressure points are likely to involve prior-art formulations containing L-cysteine, acidic parenteral solutions, aluminum control, oxygen reduction, cystine precipitation, and particle stability. Anticipation would require a single reference disclosing all limitations of an asserted claim. Obviousness may combine known cysteine formulations with known oxygen-control, low-metal, or stability techniques, but the result would depend heavily on the patent specification and prosecution record.

How strong is the patent estate?

Based on the supplied claims, the estate is strongest as a formulation-quality patent and weaker as a manufacturing monopoly.

Risk category	Assessment
Standard 50 mg/mL cysteine PN additive	High potential relevance
Neonatal or infant formulation	High potential relevance
Low-aluminum formulation	High relevance if below 150 ppb
Low-oxygen formulation	Relevant, but narrower than the base formulation claims
Long shelf life	Relevant where the product has six- to 24-month stability
Cysteine active ingredient generally	Low coverage
Cysteine synthesis or purification	No coverage shown in supplied claims
Non-parenteral cysteine products	No coverage shown
Biosimilar competition	Not applicable
Generic injectable competition	Material risk, dependent on listing and term

The claims have substantial overlap, which supports enforcement against products meeting several quality attributes. Their principal vulnerabilities are numerical ambiguity, subjective terms such as "about" and "substantially free," the meaning of "suitable for use," and proof of stability and particulate status.

Key Takeaways

US Patent 10,653,719 is directed to low-aluminum, acidic, particle-controlled L-cysteine solutions for parenteral nutrition.
The principal formulation target is approximately 50 mg/mL L-cysteine hydrochloride monohydrate or an equivalent L-cysteine amount.
Claim 1 is the broadest independent claim and does not require a neonatal indication or specified shelf life.
Claims 12 and 17 increase risk for neonatal and infant products by adding stability and low-oxygen limitations.
Aluminum thresholds range from less than approximately 150 ppb to less than approximately 10 ppb.
Dissolved oxygen limitations range from less than approximately 5 ppm to less than approximately 1 ppm, with a separate 0.4-3.8 ppm range.
The claims do not directly cover L-cysteine synthesis, purification, filling equipment, or oxygen-control processes as standalone methods.
L-cysteine is a small molecule, so generic and 505(b)(2) competition is more relevant than biosimilar competition.
The patent's exact expiration date, Orange Book listing, Paragraph IV status, litigation record, and settlement position require the corresponding USPTO, FDA, and court records.
The principal commercial exposure is a competing 50 mg/mL injectable that is acidic, low in aluminum, stable, and free of visible cystine-related particles.

Frequently Asked Questions

Does a cysteine injection with less than 150 ppb aluminum infringe automatically?

No. The product must also meet the concentration, pH, carrier, particle, and parenteral-nutrition suitability limitations, along with any additional limitations of the asserted claim.

Can a product avoid the patent by using L-cysteine instead of cysteine hydrochloride monohydrate?

Not necessarily. The claims expressly cover an equivalent amount of a pharmaceutically acceptable L-cysteine, salt, or hydrate.

Does a neonatal label create infringement risk under claim 1?

Potentially. Claim 1 does not require neonatal labeling. The neonatal limitation appears in claims 12 and 17 and their dependent claims.

Can higher dissolved oxygen avoid all claims?

No. Higher dissolved oxygen may avoid certain oxygen-dependent claims, but it does not necessarily avoid claims 1 or 12.

Is a 24-month expiration date enough to satisfy the patent?

No. The claims require more than shelf life. The product must also satisfy the composition, pH, aluminum, particle, intended-use, and, for some claims, oxygen limitations.

References

U.S. Food and Drug Administration. (2023). Aluminum in large and small volume parenterals used in total parenteral nutrition. Code of Federal Regulations, 21 C.F.R. § 201.323.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book.
U.S. Code. (2024). Hatch-Waxman patent certification and approval provisions. 21 U.S.C. § 355(j)(2)(A)(vii)-(viii), § 355(j)(5)(B)(iii).
U.S. Code. (2024). Patent term. 35 U.S.C. § 154.
U.S. Patent and Trademark Office. (2024). Maintenance fees. 37 C.F.R. §§ 1.362-1.378.
United States Patent and Trademark Office. (2020). U.S. Patent No. 10,653,719. «L-cysteine solution for parenteral nutrition use».

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Exela Pharma	ELCYS	cysteine hydrochloride	SOLUTION;INTRAVENOUS	210660-001	Apr 16, 2019		RX	Yes	Yes	10,653,719	⤷ Start Trial	Y				⤷ Start Trial
Baxter Hlthcare Corp	NOURESS	cysteine hydrochloride	SOLUTION;INTRAVENOUS	212535-001	Dec 13, 2019		RX	Yes	Yes	10,653,719	⤷ 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: 10,653,719

Which drugs does patent 10,653,719 protect, and when does it expire?

Summary for Patent: 10,653,719