United States Drug Patent 11,602,508: Claim Scope, Exclusivity, and Norepinephrine Patent Landscape

U.S. Patent No. 11,602,508 covers a ready-to-administer aqueous norepinephrine formulation designed to preserve the R-isomer without conventional antioxidants. The independent claim requires five central elements: a defined acidic pH, a defined norepinephrine concentration, a tartrate-based chelating agent, a tonicity agent, and specified R-isomer retention after storage. The patent is a formulation patent, not a method-of-treatment or manufacturing-process patent.

The broadest commercial risk applies to sterile premixed norepinephrine products containing tartrate in the claimed concentration range, particularly products using sodium chloride or dextrose for tonicity and marketed without added antioxidants.

What does U.S. Patent 11,602,508 protect?

Claim 1 protects a composition with the following mandatory limitations:

Claim element	Required scope
Dosage form	Ready-to-administer aqueous solution
pH	Between 3.7 and 4.3
Norepinephrine concentration	10 to 100 µg/mL
Initial stereochemical purity	At least 95% R-isomer by HPLC
Chelating agent	Tartrate bicarboxylic acid
Chelator concentration	10 to 100 µg/mL
Antioxidant content	Substantially free of antioxidants
Stability result	At least 90% R-isomer after at least three months at 25±2°C and 60±5% relative humidity

The claim uses “comprising,” which generally makes it open-ended. A formulation can contain additional excipients and still fall within the claim unless those additional components remove a required limitation or create a legal basis for noninfringement.

The patent does not require a particular vial, bag, syringe, container, administration route, or clinical indication in the claims supplied. It also does not require a particular norepinephrine salt in claim 1.

How do the dependent claims expand the patent’s formulation coverage?

Claims 2 through 10 create narrower positions around tonicity, dosage form, salt selection, buffering, and chelator composition.

Claim	Added limitation	Commercial significance
2	Osmolality of 260 to 340 mOsm/kg	Captures near-isotonic intravenous products
3	Pharmaceutically acceptable salt at 0.6 to 1.2 wt%	Targets conventional saline-type formulations
4	Dextrose as tonicity agent	Covers dextrose premixes
5	NaCl as tonicity agent	Covers saline premixes
6	Sterile composition	Aligns with injectable products
7	Acid, mineral salt, or organic salt of norepinephrine	Broadens norepinephrine source forms
8	Norepinephrine organic salt	Narrows claim 7
9	No added buffer	Targets self-buffered or unbuffered systems
10	Tartrate plus an aminopolycarboxylic acid	Covers dual-chelator systems

Claim 6 is commercially important because most ready-to-administer intravenous norepinephrine products are sterile. Claims 4 and 5 divide the principal commercial tonicity strategies between dextrose and sodium chloride. Claim 9 may be particularly relevant to products that rely on the intrinsic acidity of the norepinephrine and tartrate system rather than a separately added buffer.

What is the technical inventive concept of the patent?

The apparent technical focus is preservation of norepinephrine stereochemical integrity without reliance on antioxidants. Norepinephrine is supplied predominantly as the pharmacologically relevant R-isomer. The claim measures stability through retention of R-isomer content rather than only through total assay, impurity profile, or color change.

The formulation architecture combines:

An acidic pH window of 3.7 to 4.3.
Tartrate-based metal-ion control.
A tonicity adjustment suitable for administration.
No substantial amount of antioxidant.
Retention of at least 90% R-isomer after the specified storage interval.

The R-isomer limitation is narrower than a claim requiring only “norepinephrine.” A competing product could contain the same active ingredient and similar excipients but avoid the claim if its initial R-isomer content, measured by the claimed HPLC approach, falls outside the stated range or if its stability profile does not satisfy the three-month limitation.

The phrase “substantially free of antioxidants” is likely to create claim-construction and factual disputes. The claim does not provide a numerical threshold. The analysis would turn on the identity and amount of any antioxidant, the specification’s definition, and whether the accused product contains an ingredient added for antioxidant function.

How strong is the patent estate for U.S. Patent 11,602,508?

The principal strength is the combination of composition and performance limitations. A challenger must address both the recipe and the demonstrated or inherent stability result. A reference disclosing norepinephrine, tartrate, saline, and an acidic pH may not anticipate claim 1 unless it also discloses the required concentration ranges, R-isomer purity, antioxidant limitation, and stability result.

The main vulnerability is predictable formulation optimization. A validity challenge could argue that the claimed pH, tartrate concentration, tonicity range, and antioxidant exclusion would have been obvious to a skilled pharmaceutical formulator working with known norepinephrine instability. The strength of that argument would depend on the patent’s examples, comparative data, unexpected results, and the relevant prior-art disclosures.

Claim-by-claim risk profile

Issue	Likely patent significance
pH 3.7 to 4.3	Moderate narrowing limitation; easy to test
Norepinephrine 10 to 100 µg/mL	Broad commercial concentration range
R-isomer ≥95% initially	Technical limitation requiring chiral analysis
Tartrate 10 to 100 µg/mL	Core composition limitation
No substantial antioxidant	Potentially ambiguous and fact-intensive
Three-month R-isomer retention	Potentially strong if supported by comparative data
260 to 340 mOsm/kg	Captures standard injectable tonicity
0.6 to 1.2 wt% salt	Directly relevant to saline products
Sterility	Likely routine for intravenous products
No added buffer	Useful fallback claim
Aminopolycarboxylic acid	Narrower dual-chelator protection

Claims 2, 3, 4, 5, 6, and 9 provide practical fallback positions if claim 1 is narrowed or invalidated. Claims 7 and 8 are more dependent on the precise norepinephrine salt used in the product.

When does U.S. Patent 11,602,508 lose exclusivity?

U.S. Patent No. 11,602,508 issued on March 14, 2023. Its ordinary patent term is generally 20 years from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable disclaimer recorded in the patent file (35 U.S.C. §154).

The issue date alone does not establish the expiration date. The controlling date must be determined from the patent’s priority chain and USPTO patent-term calculation. Patent-term extension under 35 U.S.C. §156 is generally associated with regulatory review of approved products, but the availability and duration of any extension require a product-specific regulatory determination.

Exclusivity item	Status based on the supplied claim information
Patent issue date	March 14, 2023
Ordinary term	20 years from earliest effective nonprovisional filing date
Patent-term adjustment	Must be checked in the USPTO record
Patent-term extension	Must be checked against the approved product and regulatory record
Regulatory exclusivity	Not established by the claims
Small-molecule generic pathway	Potentially relevant
Biosimilar pathway	Not applicable to norepinephrine

Patent expiration and FDA regulatory exclusivity are separate. A patent can expire after or before regulatory exclusivity, and an FDA-listed patent may affect an ANDA applicant even when other patents remain outside the Orange Book.

What is the Orange Book status of U.S. Patent 11,602,508?

A patent is not automatically Orange Book-listed merely because it covers a drug formulation. The relevant NDA holder must submit the patent to FDA, and FDA must determine whether it claims the approved drug, a formulation or composition of the approved drug, or an approved method of use under the applicable listing rules (FDA, 2023).

Because the supplied information does not identify an NDA, trade name, holder, or Orange Book listing, the claims alone do not establish that Patent 11,602,508 is listed in the Orange Book. The patent’s formulation focus would make a formulation or composition listing the most plausible category if an approved NDA holder submitted it.

An Orange Book listing would create a potential ANDA certification issue. A Paragraph IV certification could assert that the patent is invalid, unenforceable, or not infringed. If the patent were timely listed for a reference product, an infringement suit filed within the statutory period could trigger a 30-month stay under the Hatch-Waxman framework, subject to the statute’s conditions (21 U.S.C. §355).

What Paragraph IV challenges and generic entry risks exist?

The patent creates three principal generic-entry routes:

Design around the claimed formulation.
File a Paragraph IV certification against an Orange Book-listed patent.
Wait for patent expiration or resolve the matter through litigation or settlement.

A generic developer could seek to avoid claim 1 by changing one or more of the following:

Use a pH below 3.7 or above 4.3.
Use less than 10 µg/mL or more than 100 µg/mL norepinephrine.
Use a non-tartrate chelator.
Use a tartrate concentration outside 10 to 100 µg/mL.
Include a qualifying antioxidant.
Use a formulation that does not retain at least 90% R-isomer under the claimed conditions.
Use a different active stereochemical profile, subject to regulatory and clinical requirements.
Use a formulation that is not ready-to-administer.

Design-around analysis must account for dependent claims. For example, moving away from tartrate may avoid claim 1 and claim 10, but a product using sodium chloride at 0.6 to 1.2 wt% could still implicate claims 3 and 5 if the other limitations remain present.

What formulation patents and method-of-use patents compete with this patent?

The supplied claims identify no method-of-use protection. They do not claim treatment of hypotension, septic shock, cardiac arrest, anesthesia-induced hypotension, or any other clinical use. They also do not claim administration rate, dose, patient population, or treatment duration.

The relevant competitive patent categories are:

Patent category	Relevance to Patent 11,602,508
Ready-to-use norepinephrine compositions	Directly overlapping technical area
Antioxidant-free norepinephrine formulations	Directly relevant to claim 1
Chelator-based stability systems	Directly relevant
Container and oxygen-control systems	Potentially complementary
Manufacturing and sterilization processes	Potentially independent blocking rights
Premixed infusion bags and syringes	Commercially relevant delivery claims
Method-of-use patents	Not covered by the supplied claims
Salt and polymorph patents	Potentially relevant to claims 7 and 8

A complete freedom-to-operate review must separate composition claims from process, container, labeling, and method-of-use claims. Avoiding Patent 11,602,508 would not eliminate risk from an unrelated patent covering manufacture, packaging, sterilization, or a specific norepinephrine product.

What manufacturing and IP barriers does the patent create?

The patent may affect development even if a competitor believes it can avoid literal infringement. The critical manufacturing controls include:

Chiral purity of the norepinephrine starting material.
Tartrate identity and concentration.
Final pH adjustment.
Tonicity and osmolality.
Oxygen exposure during compounding and filling.
Container closure integrity.
Sterilization compatibility.
Stability testing under the specified temperature and humidity conditions.
HPLC method validation for R-isomer retention.

The three-month stability limitation creates a development burden. A challenger would need reliable analytical data showing that the commercial formulation does not satisfy the limitation or that the limitation is not inherent in the accused product. Stability results may vary with container, headspace, light exposure, fill volume, sterilization method, and analytical method.

Which companies are challenging the patent, and what litigation affects it?

The claim text alone does not establish any Paragraph IV filing, ANDA litigation, licensing transaction, settlement agreement, or district-court proceeding involving Patent 11,602,508. Those matters are separate from the patent grant and must be verified through USPTO, FDA, PACER, and settlement records.

No biosimilar risk exists because norepinephrine is a chemically synthesized small molecule, not a biological product regulated through the biosimilar pathway. The relevant competitive threat is generic or authorized-generic entry, not biosimilar substitution.

How does Patent 11,602,508 compare with conventional norepinephrine products?

Attribute	Claimed formulation	Conventional product risk
Ready-to-administer	Required	Premixed products are most exposed
Tartrate chelator	Required	Products using alternative chelators may avoid claim 1
Antioxidant-free	Required	Antioxidant-containing products may avoid claim 1
R-isomer retention	Required	Requires chiral stability evidence
Saline tonicity	Covered by dependent claim 5	High relevance to NaCl products
Dextrose tonicity	Covered by dependent claim 4	High relevance to dextrose products
Sterility	Covered by claim 6	Most injectable products likely meet it
Added buffer	Excluded by claim 9	Buffered products may avoid claim 9 but not necessarily claim 1
Biological product	No	Biosimilar framework does not apply

Key Takeaways

U.S. Patent 11,602,508 is directed to a ready-to-administer norepinephrine formulation, not a treatment method.
Claim 1 requires pH 3.7 to 4.3, norepinephrine at 10 to 100 µg/mL, tartrate at 10 to 100 µg/mL, substantial absence of antioxidants, initial R-isomer content of at least 95%, and retention of at least 90% R-isomer after three months under specified conditions.
Claims 2 through 10 materially increase exposure for isotonic, sterile, saline, dextrose, unbuffered, and organic-salt products.
The patent issued March 14, 2023. Its exact expiration date cannot be determined from the claim text alone because the priority chain and term adjustments control.
Orange Book listing, Paragraph IV activity, litigation, licensing, and settlement status are not established by the supplied claims.
Generic design-around opportunities exist, but changing one excipient may not avoid all dependent claims.
No biosimilar pathway applies. The commercial threat is generic entry.
The strongest technical dispute is likely to involve the meaning of “substantially free of antioxidants,” the scope of “tartrate bicarboxylic acid,” and whether R-isomer retention is inherent in an accused product.

FAQs About U.S. Patent 11,602,508

Does the patent cover all norepinephrine injections?

No. The claims are limited to specific ready-to-administer aqueous compositions containing tartrate, defined pH and concentration ranges, and specified R-isomer stability.

Can a norepinephrine product with sodium chloride infringe?

Yes. Sodium chloride is expressly recited in claim 5. The product must also satisfy the limitations inherited from claim 1 and, for claim 3, the specified salt concentration range.

Does adding an antioxidant automatically avoid infringement?

Not necessarily. The effect depends on the construction of “substantially free of antioxidants” and whether the product still satisfies the remaining claim limitations. An added ingredient may also create separate regulatory or formulation consequences.

Is a product with dextrose covered?

Potentially. Claim 4 expressly recites dextrose as the tonicity agent. The product must also meet the limitations inherited from claim 1.

Does the patent block a norepinephrine manufacturing process?

Not based on the supplied claims. The claims are composition claims. Separate unreviewed claims in the patent family or other patents could cover manufacturing, sterilization, packaging, or filling processes.

References

United States Patent No. 11,602,508. (2023). United States Patent and Trademark Office.
Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
Food and Drug Administration. (2023). FDA’s Orange Book patent listing requirements and related patent information. U.S. Department of Health and Human Services.
21 U.S.C. §355. Abbreviated applications and patent certifications.
35 U.S.C. §154. Contents and term of patents; provisional rights.
35 U.S.C. §156. Extension of patent term.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Long Grove Pharms	NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE	norepinephrine bitartrate	SOLUTION;INTRAVENOUS	214628-001	Oct 6, 2022		RX	Yes	Yes	11,602,508	⤷ Start Trial	Y				⤷ Start Trial
Long Grove Pharms	NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE	norepinephrine bitartrate	SOLUTION;INTRAVENOUS	214628-002	Oct 6, 2022		RX	Yes	Yes	11,602,508	⤷ Start Trial	Y				⤷ Start Trial
Long Grove Pharms	NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE	norepinephrine bitartrate	SOLUTION;INTRAVENOUS	214628-003	Oct 6, 2022		RX	Yes	Yes	11,602,508	⤷ 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	3051467	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2018140894	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,602,508

Which drugs does patent 11,602,508 protect, and when does it expire?

Summary for Patent: 11,602,508