US Patent 10,702,490: Cysteine Hydrochloride Solution Claims, Exclusivity, and Patent Landscape

US Patent 10,702,490 protects a low-pH, high-concentration cysteine hydrochloride solution and a controlled oxygen-management manufacturing process. The broadest claim covers a solution containing approximately 40-60 mg/mL cysteine hydrochloride at pH 1.0-1.5, prepared by acidifying water, dissolving cysteine hydrochloride, and filling and sealing the container under inert gas. Dependent claims add stability, impurity, oxygen, aluminum, filtration, temperature, and container limitations.

The patent is commercially relevant to cysteine hydrochloride injection products used as a cysteine source in parenteral nutrition, including Exela Pharma Sciences' Elcys product. Its strongest practical coverage is concentrated in the combination of 50 mg/mL concentration, very acidic pH, low cystine and dissolved oxygen, low aluminum, sterile filtration, inert-gas processing, and silica-lined glass packaging.

The expected nominal patent expiration is in December 2035, subject to any applicable patent-term adjustment or extension. Cysteine hydrochloride is a small-molecule drug, so biosimilar law does not apply. Generic competition would proceed through an ANDA, most likely with a Paragraph IV certification if the relevant patent remains listed and the applicant seeks approval before expiry.

What does US Patent 10,702,490 protect?

The patent protects both a cysteine hydrochloride composition and a method-defined manufacturing profile. Claim 1 is the independent claim and establishes the principal infringement framework.

Claim element	Scope
Active ingredient	Cysteine hydrochloride
Concentration	About 40-60 mg/mL
pH	About 1.0-1.5
Acidification step	Water is acidified to pH 1.0-1.5 before drug dissolution
Filling operation	Container is filled and sealed under inert-gas flow
Dosage form	A solution in a sealed container, rather than a dry powder or unconstrained bulk solution

The claim does not require every optional feature later recited in dependent claims. A product that meets the concentration, pH, and process elements can potentially fall within claim 1 even if it does not have the claimed aluminum, oxygen, cystine, storage, filtration, or vial characteristics.

The claims are drafted around the stated technical problem: cysteine hydrochloride is oxidation-sensitive, can form cystine, can develop visible particulates, and can accumulate aluminum from materials used in pharmaceutical processing or packaging. The patent addresses those risks through acidic conditions, oxygen exclusion, sterile filtration, controlled filling, and container selection. (U.S. Patent No. 10,702,490, 2020)

How broad is independent claim 1?

Claim 1 has two distinct components:

A composition limitation.
A preparation limitation embedded in a product claim.

The composition must contain approximately 40-60 mg/mL cysteine hydrochloride and have a pH of approximately 1.0-1.5. The preparation must include acidifying water, dissolving the drug in the acidified water, and filling and sealing under inert gas.

The range language is significant. “About” creates a degree of numerical flexibility, but it does not eliminate the need for a product to be reasonably close to the claimed ranges. A formulation at 50 mg/mL and pH 1.1 is squarely within the claim. A formulation at 30 mg/mL or pH 2.0 would present a stronger noninfringement position, subject to claim construction and equivalents analysis.

Product-by-process implications

Claim 1 is not limited solely to a free-standing solution defined by composition. It also describes how the solution is made. In U.S. patent law, a product-by-process limitation may be relevant where the accused product has the claimed process characteristics or where the process produces a product that cannot be materially distinguished from the claimed product. The significance of the process language would depend on the patent's prosecution history, claim construction, and the evidence concerning whether the process changes the final solution.

A generic manufacturer could therefore attempt to design around the process limitations by:

Acidifying the water after dissolving cysteine hydrochloride.
Performing the filling operation without inert-gas flow.
Using a different oxygen-control process.
Starting with a pre-acidified solvent or a prepared acidic vehicle.
Using a different packaging and sealing sequence.

Those approaches would not automatically eliminate risk because the doctrine of equivalents, prosecution-history estoppel, and product comparability may remain relevant.

What do dependent claims 2 through 30 add?

The dependent claims create narrower positions around stability and manufacturing controls. They also provide fallback claims if broad claim 1 is challenged.

Stability and particulate claims

Claims 2-6 require the solution to be free of visible particulate matter. Claims 3-6 add storage periods of six, 12, 18, or 24 months at 25°C and 60% relative humidity.

These claims are useful against products that meet the composition and process limitations but show particulate formation during storage. The 24-month claim is commercially important because it corresponds to a typical long-term shelf-life target.

The claims do not merely require initial clarity. Claims 3-6 require the specified particulate-free condition after defined storage periods. A challenger would likely examine:

Initial and aged visual inspection results.
Container-closure integrity.
Stability protocols.
Sampling plans.
Particulate detection methods.
Whether the claimed storage condition is part of the marketed product's labeled shelf life.

Cystine and oxygen limitations

Claim 7 requires cystine content of less than approximately 1% by weight of total cysteine. Cystine is the principal oxidation product formed when cysteine oxidizes.

Claim 8 requires dissolved oxygen below 2 mg/L. Claims 24-26 provide related process limitations:

Acidification under inert-gas flow.
Sparging water to reduce dissolved oxygen below 2 mg/L.
Stirring during dissolution under inert-gas flow.

These claims connect final product quality to process controls. A competing product could meet the final cystine limitation while using a different oxygen-control method. Conversely, a product could use inert gas but fail the claimed dissolved-oxygen or cystine threshold.

pH subranges

Claims 9-11 narrow the pH to:

1.0-1.4.
1.0-1.3.
1.0-1.2.

The pH 1.0-1.2 range is the narrowest and likely most commercially relevant for a formulation designed around oxidation control. A product at pH 1.25 could fall within claims 9 and 10 but not claim 11.

Aluminum limitations

Claims 12-18 impose aluminum limits ranging from less than 200 μg/L to less than 10 μg/L. Claims 19-22 require aluminum below 145 μg/L after six to 24 months of storage.

Claim group	Aluminum limitation
Claim 12	Less than about 200 μg/L
Claim 13	Less than about 145 μg/L
Claim 14	Less than about 100 μg/L
Claim 15	Less than about 30 μg/L
Claim 16	Less than about 10 μg/L
Claim 17	About 0-100 μg/L
Claim 18	About 0-30 μg/L
Claims 19-22	Less than about 145 μg/L after defined storage periods

The aluminum claims may be particularly relevant to container and manufacturing-equipment selection. A generic product could avoid some claims by using a formulation or packaging system that produces higher aluminum levels, but that could create regulatory or product-quality problems. Aluminum exposure is regulated in parenteral nutrition products, making low-aluminum performance commercially valuable even where it is not required for basic approval.

Concentration, filtration, and packaging

Claim 23 narrows the concentration to about 50 mg/mL, which corresponds to the principal commercial strength of cysteine hydrochloride injection products.

Claims 27 and 28 require sterile filtration, including passage through at least one 0.22 μm filter. Claim 29 requires acidification, dissolution, and filling and sealing at ambient temperature. Claim 30 requires a silica-lined glass vial.

These limitations create a layered estate:

Claim 1 covers the central formulation and inert-gas filling sequence.
Claims 23, 27, and 28 cover the commercial concentration and sterile-filtration process.
Claim 30 covers a particular container configuration.
Claims 7, 8, and 12-22 cover quality attributes that can be tested in the finished product.

What is the likely patent expiration date?

The patent's expected nominal expiration is in December 2035, based on the patent's underlying priority and filing history. The actual enforceable expiration could differ because of patent-term adjustment, patent-term extension, terminal disclaimers, or other USPTO-record events.

Milestone	Date or period
Earliest relevant priority	2015
U.S. patent grant	July 7, 2020
Expected nominal expiry	December 2035
Possible earlier market entry	Settlement, invalidity, noninfringement, or regulatory approval outcome
Possible later expiry	Patent-term adjustment or extension, if granted

The grant date does not determine patent expiry. A generic applicant may file an ANDA before expiry and challenge the patent through Paragraph IV certification.

What is the Orange Book status of cysteine hydrochloride products?

Cysteine hydrochloride injection is an FDA-approved small-molecule product used as an additive to amino acid solutions in parenteral nutrition. The FDA-approved product associated with the patent is commonly identified with Elcys and Exela Pharma Sciences. FDA approval and Orange Book information should be evaluated together because FDA listing status, patent listing, and regulatory exclusivity are separate issues. (U.S. Food and Drug Administration, n.d.-a; U.S. Food and Drug Administration, n.d.-b)

Patent listing analysis should address:

Whether U.S. Patent 10,702,490 is listed for the relevant NDA.
The listed patent-use code, if any.
The listed expiration date.
Whether the patent is listed for the formulation, method of use, or both.
Whether the product's labeling matches the claimed concentration and dosage form.

The claims supplied here are primarily formulation and manufacturing claims. They do not recite a therapeutic disease-treatment method. An Orange Book listing, if present, would therefore be expected to relate to the approved drug product or formulation rather than a conventional method-of-use code.

When does cysteine hydrochloride lose exclusivity?

Patent expiry and regulatory exclusivity operate on separate clocks.

Exclusivity type	Relevance
New chemical entity exclusivity	Unlikely to apply because cysteine hydrochloride is an established active ingredient
Three-year new clinical investigation exclusivity	Could apply to an NDA supported by qualifying clinical investigations, but does not block all ANDA activity in the same way as NCE exclusivity
Orphan-drug exclusivity	Not apparent from the product's general parenteral-nutrition indication
Patent exclusivity	The principal barrier is the 10,702,490 patent and any related patents
Pediatric exclusivity	Would require a specific FDA grant and would extend qualifying listed patents by six months
Regulatory exclusivity end	Must be confirmed from the FDA product record
Patent end	Expected in December 2035, subject to term adjustments

The commercial loss-of-exclusivity date is therefore not necessarily the patent expiration date. A generic could enter earlier through a license or settlement, while a listed patent could remain enforceable after regulatory exclusivity ends.

Which companies are challenging US Patent 10,702,490?

No Paragraph IV challenger or district-court litigation is identified in the sources cited for this assessment.

The likely competitive set includes:

ANDA applicants seeking approval for cysteine hydrochloride injection.
Outsourced sterile-injectable manufacturers.
Parenteral-nutrition suppliers developing alternative cysteine presentations.
International manufacturers seeking U.S. approval.
Compounded-product suppliers operating outside the approved-drug model.

A Paragraph IV challenge would likely attack one or more of the following:

Obviousness of combining acidic pH with inert-gas processing.
Lack of written description or enablement across the 40-60 mg/mL and pH 1.0-1.5 ranges.
Indefiniteness of “about,” “ambient temperature,” and “free of visible particulate matter.”
Whether the product-by-process limitations distinguish the claimed solution.
Anticipation by earlier cysteine hydrochloride formulations or parenteral-nutrition preparations.
Lack of proof that the claimed process produces a patentably distinct product.

The patent holder would likely respond that the combination of low pH, oxygen control, low cystine, reduced particulates, aluminum control, and long-term stability was not disclosed or reasonably predictable from earlier formulations.

How strong is the patent estate?

US Patent 10,702,490 has moderate-to-strong commercial relevance but a narrower legal footprint than a broad composition-of-matter patent.

Strength factor	Assessment
Active ingredient coverage	Weak as a composition-of-matter right because cysteine hydrochloride is established
Concentration coverage	Strong around the 40-60 mg/mL range
pH coverage	Strong around pH 1.0-1.5, with narrower fallback ranges
Manufacturing coverage	Meaningful, particularly for inert-gas filling and oxygen control
Product-quality coverage	Meaningful for cystine, particulate, aluminum, and dissolved oxygen limits
Packaging coverage	Narrower because claim 30 requires silica-lined glass
Design-around potential	Moderate
Evidence burden	High for oxygen, aluminum, stability, and particulate limitations
Litigation leverage	Higher where the marketed product closely matches the claimed 50 mg/mL formulation and process

The patent is stronger as a product-and-process combination than as a broad monopoly over all cysteine hydrochloride injections. A competing product that uses the same 50 mg/mL strength, very low pH, inert-gas filling, sterile filtration, and glass-vial presentation could face substantial claim-overlap risk.

What formulations are protected?

The central protected formulation has the following profile:

Attribute	Core claim	Narrow commercial embodiments
Cysteine hydrochloride	40-60 mg/mL	Approximately 50 mg/mL
pH	1.0-1.5	1.0-1.2
Cystine	Not required by claim 1	Less than 1%
Dissolved oxygen	Not required by claim 1	Less than 2 mg/L
Aluminum	Not required by claim 1	Less than 10, 30, 100, or 145 μg/L
Particulates	Not required by claim 1	None after up to 24 months
Filtration	Not required by claim 1	At least one 0.22 μm filter
Container	Not required by claim 1	Silica-lined glass vial

The claims do not expressly require a particular acid, buffer, preservative, tonicity agent, or amino-acid admixture. This omission may give the patent holder meaningful coverage across multiple acidic vehicles, provided the product and process meet the claimed limitations.

What manufacturing and IP barriers affect generic entry?

The principal barriers are technical reproducibility and proof of equivalence.

A generic manufacturer would need to control:

Oxygen ingress during compounding and filling.
Oxidation of cysteine to cystine.
Aluminum leaching from equipment, closures, or glass.
Visible and subvisible particulate formation.
Sterile filtration performance at high cysteine concentration.
Container-closure integrity.
Long-term stability at the labeled storage condition.
Compatibility with amino-acid solutions used in parenteral nutrition.

A formulation that avoids the patent by changing pH or concentration may require a different regulatory strategy. If the product no longer matches the reference listed drug in formulation, strength, route, dosage form, or labeling, an ANDA may be unavailable or may require additional FDA review.

What litigation and settlement risks exist?

The most likely litigation trigger would be an ANDA containing a Paragraph IV certification against the patent. The patent holder could sue within 45 days of receiving notice, potentially triggering a 30-month stay of final approval under the Hatch-Waxman framework, subject to statutory exceptions and court action. (Food, Drug, and Cosmetic Act, 21 U.S.C. § 355)

Potential settlement structures include:

A licensed entry date before patent expiry.
A royalty-bearing license.
A volume-limited or channel-limited launch.
A settlement tied to noninfringing formulation or manufacturing changes.
A covenant not to sue for a defined product configuration.

No public settlement agreement is identified in the cited record. Any settlement would materially change the practical exclusivity date even if the patent remains formally valid.

How does US Patent 10,702,490 compare with competing patent estates?

Cysteine hydrochloride has little room for a conventional active-ingredient patent estate because the molecule is old. Competitive differentiation is more likely to arise from:

Stable injectable formulations.
Low-aluminum parenteral-nutrition products.
Container systems.
Manufacturing controls.
Premixed nutrition products.
Alternative concentrations or presentations.
Hospital-use packaging and administration systems.

Estate type	Typical scope	Competitive significance
Active ingredient patent	Cysteine hydrochloride itself	Low
Formulation patent	Concentration, pH, excipients, impurity profile	High for approved injectable products
Process patent	Oxygen exclusion, filtration, filling, sealing	Moderate to high
Container patent	Vial, closure, coating, silica lining	Moderate
Method-of-use patent	Use in parenteral nutrition or a patient population	Limited unless specifically listed
Trade secret	Manufacturing parameters and quality controls	High but difficult to enforce against independent development

US Patent 10,702,490 is most important when combined with regulatory sameness requirements. Even if a generic can design around a claim, the alternative formulation must still satisfy FDA requirements for quality, stability, sterility, and therapeutic equivalence.

What is the generic launch risk?

The generic launch risk is best characterized as delayed but technically manageable.

Earliest launch scenarios

Scenario	Commercial result
No ANDA challenge	Entry generally deferred until patent expiry or delisting
Paragraph IV challenge succeeds	Approval and launch could occur before nominal expiry
Paragraph IV litigation settles	Entry date depends on settlement terms
Design-around succeeds	Earlier launch may be possible if FDA accepts the alternative
Patent invalidated or held not infringed	Early entry becomes possible
Patent remains valid and infringed	Entry is likely blocked until expiry or license

A first-filer could obtain 180-day generic exclusivity if statutory conditions are met, creating a temporary duopoly rather than immediate broad generic competition. The commercial value of that exclusivity depends on the size of the cysteine hydrochloride injection market and hospital contracting dynamics.

What is the revenue exposure?

The patent's revenue exposure is concentrated in the approved cysteine hydrochloride injection product and related hospital or parenteral-nutrition sales. The patent does not cover cysteine in every pharmaceutical form, nutritional supplement, or compounded preparation.

Revenue exposure depends on:

Product share in U.S. parenteral nutrition.
Hospital and group-purchasing contracts.
Availability of alternative cysteine products.
Shortage conditions.
Generic manufacturing capacity.
Reimbursement and purchasing dynamics.
Whether a challenger can supply a sterile injectable at scale.

The strongest exposure would occur if the patented product is the principal commercial source of ready-to-use cysteine hydrochloride injection in the U.S. market. Small sterile-injectable markets can remain commercially concentrated even after patent expiry because manufacturing validation, inspection readiness, and supply reliability create barriers beyond patent rights.

What geographic coverage does the patent provide?

US Patent 10,702,490 provides rights in the United States only. It does not directly block manufacture, sale, or use outside the United States.

Geographic risk must be assessed separately for:

Canada.
Europe.
Japan.
China.
Australia.
Other markets where related national-phase patents were filed.

Related international or foreign patents may have different claims, expiration dates, prosecution histories, and validity profiles. A U.S. design-around may still infringe a foreign counterpart, while a formulation licensed outside the United States may not be covered domestically.

Key Takeaways

US Patent 10,702,490 covers cysteine hydrochloride solutions at approximately 40-60 mg/mL and pH 1.0-1.5, prepared through acidified water, controlled dissolution, and inert-gas filling and sealing.
The commercially important embodiment is approximately 50 mg/mL cysteine hydrochloride at a highly acidic pH.
Dependent claims add low cystine, low dissolved oxygen, low aluminum, particulate-free stability, sterile filtration, ambient-temperature processing, and silica-lined glass packaging.
The expected nominal expiration is December 2035, subject to patent-term adjustment or extension.
The patent is not a composition-of-matter patent on cysteine hydrochloride and therefore does not provide broad control over every cysteine product.
Generic risk is concentrated in ANDA applicants developing a product that matches the reference product while changing the claimed process or quality attributes.
Cysteine hydrochloride is a small molecule; biosimilar pathways do not apply.
No Paragraph IV litigation or public settlement is identified in the cited record.
Manufacturing and quality-control barriers may delay competition even after a legal design-around is developed.

FAQs About US Patent 10,702,490

Does US Patent 10,702,490 cover cysteine hydrochloride powder?

No. The claims are directed to a cysteine hydrochloride solution and its preparation. A dry powder product would not meet the solution limitations of claim 1, although other patents or regulatory requirements could apply.

Can a generic avoid the patent by using a pH above 1.5?

Potentially, but the alternative product must still satisfy FDA requirements and avoid infringement under both literal-infringement and equivalents theories. A pH outside the claimed range would not by itself eliminate all legal risk.

Is a silica-lined glass vial required for every patented product?

No. The silica-lined glass vial is required only by claim 30. Claims 1-29 do not require that specific container.

Does the patent cover compounded cysteine hydrochloride?

The claims do not expressly exclude compounded products. Infringement would depend on whether the compounded solution meets the claim limitations and whether the relevant acts fall within the patent's statutory scope.

Could a manufacturer use nitrogen only during filling and avoid the patent?

Not necessarily. Claim 1 requires filling and sealing under inert-gas flow, while other claims address inert-gas use during acidification, sparging, and dissolution. The complete manufacturing sequence and final product characteristics would determine claim overlap.

References

Exela Pharma Sciences, LLC. (2020). Elcys (cysteine hydrochloride injection) prescribing information. U.S. Food and Drug Administration.

Food and Drug Administration. (n.d.-a). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

Food and Drug Administration. (n.d.-b). Drugs@FDA: FDA-approved drugs. U.S. Department of Health and Human Services.

U.S. Patent No. 10,702,490. (2020). Cysteine hydrochloride solution and methods of making same. United States Patent and Trademark Office.

U.S. Food and Drug Administration. (n.d.-c). FDA guidance and statutory framework for abbreviated new drug applications and patent certifications. U.S. Department of Health and Human Services.

United States Code, 21 U.S.C. § 355. (2024). New drugs and abbreviated applications.

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	10,702,490	⤷ 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: 10,702,490

Which drugs does patent 10,702,490 protect, and when does it expire?

Summary for Patent: 10,702,490