US Patent 10,016,407: Scope, Claim Construction, Exclusivity and Generic-Entry Risk

US Patent 10,016,407 protects a narrow method of using a ready-to-use cocaine hydrochloride nasal composition in patients with hepatic or renal impairment. The patent does not claim cocaine hydrochloride generally, a nasal composition standing alone, or every use of the Numbrino product. Its commercial value lies in the combination of a defined formulation, pledget-based nasal administration, procedure timing, and an impaired-patient population.

The patent has a reported expiration date of June 8, 2035, subject to the patent-term calculation recorded by the USPTO. Numbrino received FDA approval on December 14, 2018, and its regulatory exclusivity period has expired. The remaining barrier is therefore patent-based, primarily through the listed method-of-use coverage and any other patents associated with the product. [1]-[3]

What does US Patent 10,016,407 protect?

The patent protects two overlapping method-of-administration claim sets.

Claim group	Required formulation	Required patient population	Administration requirements
Claims 1-10	3.6%-4.4% cocaine hydrochloride; 0.07%-0.20% sodium benzoate; acidulant; water; optional coloring additive	Hepatic or renal impairment	About 4 mL soaked into one or more pledgets; pledgets placed on nasal mucosa for up to 20 minutes and removed
Claims 11-20	3.6%-4.4% cocaine hydrochloride; preservative; 0.01%-1.0% citric acid; water; optional coloring additive	Hepatic or renal impairment	About 4 mL soaked into one or more pledgets; pledgets placed on nasal mucosa for up to 20 minutes and removed

The claims are method claims. A product manufacturer does not necessarily infringe merely by making or selling a cocaine hydrochloride nasal solution. Infringement generally requires performance of the claimed method, inducement of that method, or contribution to its performance under the applicable patent statutes. [4]

How should the independent claims be construed?

Claim 1

Claim 1 requires all of the following:

Administration of a local anesthetic.
Administration before a diagnostic or surgical procedure.
A subject with hepatic or renal impairment.
A ready-to-use composition.
Approximately 4 mL of composition.
Cocaine hydrochloride at approximately 3.6%-4.4%.
Sodium benzoate at approximately 0.07%-0.20%.
An acidulant.
Water.
Soaking one or more pledgets.
Contacting each pledget with nasal mucous membrane.
Contact for up to 20 minutes.
Removing each pledget.

The composition limitation is narrower than a generic reference to a 4% cocaine solution. The sodium benzoate range is material. A formulation containing 4% cocaine hydrochloride but no sodium benzoate, or sodium benzoate outside the claimed range, would create a non-infringement argument under the literal claim language, subject to the doctrine of equivalents.

Claim 11

Claim 11 uses a different formulation definition. It requires:

Cocaine hydrochloride at approximately 3.6%-4.4%;
A preservative;
Citric acid at approximately 0.01%-1.0%;
Water;
Optional coloring additive;
The same 4 mL pledget-based nasal administration;
The same hepatic or renal impairment population.

Claim 11 is broader than claim 1 with respect to the preservative because it does not specify sodium benzoate. Claim 20 narrows that branch by specifying sodium benzoate as the preservative.

A formulation may fall within both independent claims if it contains sodium benzoate within the claim 1 range and citric acid within the claim 11 range. The two claims are therefore overlapping rather than mutually exclusive.

What formulations are protected by US 10,016,407?

The formulation coverage is directed to a near-4% cocaine hydrochloride nasal solution used in a clinical setting.

Quantitative scope

The principal concentration ranges are:

Component	Claim 1	Claim 11
Cocaine hydrochloride	About 3.6%-4.4%	About 3.6%-4.4%
Sodium benzoate	About 0.07%-0.20%	Not specifically required
Preservative	Not separately stated beyond sodium benzoate	Required, but not limited in claim 11
Citric acid	Acidulant, not quantitatively limited	About 0.01%-1.0%
Water	Required	Required
Coloring additive	Optional	Optional
Volume	About 4 mL	About 4 mL

At a nominal 4% concentration, 4 mL contains approximately 160 mg of cocaine hydrochloride. The claimed 3.6%-4.4% range corresponds approximately to 144-176 mg in a 4 mL volume, assuming percentage weight/volume interpretation consistent with the commercial product labeling.

The word "about" creates a claim-construction issue. Courts typically assess the intrinsic evidence, specification, prosecution history, analytical precision, and whether the accused concentration performs the same claimed function. A formulation at 4.5% is not automatically outside the claim, but it would require analysis of the patent record and the technical meaning of "about."

Ready-to-use limitation

"Ready-to-use composition" distinguishes the claimed method from a method requiring reconstitution, dilution, or extemporaneous compounding before administration. A prefilled or immediately usable solution is more likely to satisfy this limitation than a concentrated stock solution requiring manipulation.

Pledget limitation

The patent requires soaking pledgets and placing each pledget on the nasal mucous membrane. Administration by spray, atomizer, syringe, gel, or another delivery device may avoid literal infringement of the pledget limitations, although induced-infringement and equivalents theories would depend on the product labeling, instructions, and technical facts.

Does the patent cover hepatic and renal impairment separately?

Yes. The independent claims use the disjunctive phrase "hepatic or renal impairment." The dependent claims then divide the population into separate subgroups.

Patient subgroup	Relevant claims
Any hepatic impairment	Claims 1-5 and 11-15
Child-Pugh Grade B	Claims 4 and 14
Child-Pugh Grade C	Claims 5 and 15
Any renal impairment	Claims 1, 6-8 and 11, 16-18
Renal impairment with increased systemic exposure	Claims 7 and 17
eGFR approximately 15-29 mL/min/1.73 m²	Claims 8 and 18

The dependent claims do not replace the limitations of the independent claims. For example, claim 8 still requires the composition, pledget procedure, volume, concentration, timing, and removal limitations from claim 1.

The claims also create a potential scope distinction between impairment as a clinical diagnosis and impairment demonstrated by increased systemic exposure. Claims 1 and 6 cover the impairment categories without expressly requiring proof of increased exposure. Claims 3, 7, 13, and 17 add that pharmacokinetic condition.

Does US 10,016,407 cover nasal endoscopy?

Yes. Claims 9 and 19 expressly identify nasal endoscopy as the procedure. The independent claims are broader because they cover diagnostic or surgical procedures generally. Nasal endoscopy is therefore a specific, commercially relevant embodiment rather than the full procedural scope.

The claims do not appear limited to a particular type of endoscope, healthcare setting, operator, or underlying nasal diagnosis. The method remains subject to the hepatic or renal impairment, formulation, pledget, volume, contact-time, and removal limitations.

When does US Patent 10,016,407 lose exclusivity?

The reported patent expiration date is June 8, 2035. That date is substantially later than the expiration of Numbrino's FDA regulatory exclusivity.

Event	Date or period
Earliest reported priority date	June 8, 2015
US patent grant	June 26, 2018
Numbrino FDA approval	December 14, 2018
Reported patent expiration	June 8, 2035
Three-year FDA exclusivity	Expired in December 2021
Earliest ordinary patent-free date	After expiration, absent invalidation, disclaimer, or other legal change

A patent's enforceable term can be affected by patent-term adjustment, terminal disclaimers, disclaimers, reexamination, or post-grant proceedings. The USPTO patent record controls the operative term. [1]

Because cocaine hydrochloride is an established active ingredient rather than a newly discovered chemical entity, the principal FDA exclusivity issue was not a five-year new chemical entity period. Numbrino's approval was associated with clinical-investigation exclusivity, generally lasting three years from approval under the applicable FDA pathway. That regulatory period does not block an ANDA forever and does not substitute for the patent estate. [2]-[5]

What is the Orange Book status of US 10,016,407?

US 10,016,407 has been associated with the Numbrino product and its use in nasal procedures. Orange Book treatment must be evaluated by product listing, patent number, patent-use code, and the current FDA publication.

The relevant distinction is between:

A formulation patent, which can restrict the composition itself;
A method-of-use patent, which can restrict a labeled or induced use;
A drug-substance or manufacturing patent, which can restrict API production or processing.

US 10,016,407 is principally a method-of-use patent with embedded formulation limitations. Its practical effect depends heavily on whether an ANDA applicant seeks approval for the patented impaired-patient use and how the reference listed drug's labeling describes that population.

An ANDA applicant may use a Paragraph IV certification to assert that the patent is invalid, unenforceable, or not infringed. It may also use a section viii statement to carve out a patented method of use when the remaining proposed labeling does not encourage that use. The viability of a carve-out depends on the Orange Book use code and whether the labeling can omit the patented indication without creating an incomplete or misleading label. [3]-[5]

What Paragraph IV challenges could target this patent?

A Paragraph IV challenge would likely focus on claim construction, written description, enablement, obviousness, anticipation, and infringement.

Likely invalidity theories

Issue	Potential argument
Anticipation	Prior art discloses a near-4% cocaine nasal solution, pledget administration, procedure use, and impaired patients in one reference
Obviousness	A skilled person would combine known cocaine nasal anesthesia, standard pledget administration, and pharmacokinetic precautions for hepatic or renal impairment
Written description	The specification does not adequately support the full breadth of "hepatic or renal impairment," all preservatives, or the full quantitative ranges
Enablement	The disclosure does not enable the full range of formulations and patient conditions without undue experimentation
Indefiniteness	Terms such as "about," "ready-to-use," and "increased systemic exposure" lack sufficiently definite boundaries
Infringement	The generic product label omits impaired patients, uses a different delivery system, or uses a formulation outside the claimed ranges

The strongest practical defense for the patent is the combined limitation structure. A challenger must address not merely cocaine nasal anesthesia, but the specific intersection of formulation, pledget use, contact time, procedure, and impaired-patient population.

The strongest vulnerability is that the claims combine known product and administration features with a patient subgroup defined by organ impairment. If the prior art disclosed the same product instructions and pharmacokinetic concern, the incremental patentability argument could be contested.

What generic launch scenarios exist?

Scenario 1: Paragraph IV challenge

An ANDA applicant could certify that US 10,016,407 is invalid or not infringed. The patent holder could sue within 45 days, triggering a statutory stay of FDA approval for up to 30 months, subject to exceptions and court developments. [4]

This pathway creates the earliest realistic challenge to the patent, but the commercial launch date would depend on litigation timing, the court's claim construction, and whether the applicant receives a favorable judgment.

Scenario 2: Section viii carve-out

An applicant could omit the patented impaired-patient method from its label if the remaining label supports approval without promoting that use. This strategy is more difficult where the reference labeling, dosing instructions, or safety information directly encourages use in hepatic or renal impairment.

The method's detailed clinical population makes the use-code analysis important. A narrow use code may facilitate a carve-out. A broad use code covering the overall nasal-procedure indication may make a clean carve-out more difficult.

Scenario 3: Non-infringing formulation or administration

A competitor could seek approval for a product or label that avoids one or more limitations, such as:

A concentration outside approximately 3.6%-4.4%;
No sodium benzoate within 0.07%-0.20%;
A preservative system outside the claim 11 scope;
A delivery device other than pledgets;
A procedure label that excludes the claimed population;
A contact time or volume outside the claimed parameters.

Each design-around must be assessed against all asserted claims and the doctrine of equivalents.

How strong is the patent estate for Numbrino?

US 10,016,407 is commercially meaningful but technically narrow. Its strength can be characterized as follows:

Factor	Assessment
Claim type	Method of use
Product dependence	High
Patient-population specificity	High
Formulation specificity	Moderate to high
Delivery-method specificity	High
Direct composition blocking power	Low
Relevance to labeled use	Potentially high
Design-around potential	Moderate
Regulatory exclusivity remaining	None based on the expired three-year period
Reported patent life	Through June 8, 2035

The patent is strongest against a generic that copies the reference product, retains pledget administration, and seeks a label encompassing impaired patients undergoing nasal procedures. It is weaker against a product using a different delivery route or a label that successfully omits the patented method.

What patent litigation and settlement risks affect the product?

The supplied claim set does not establish a filed Paragraph IV case, settlement, license, or covenant not to sue. Those events cannot be inferred from the patent text.

A litigation review should distinguish among:

ANDA litigation under 21 U.S.C. § 355(j);
Declaratory-judgment actions;
Patent Office post-grant proceedings;
Contract disputes involving commercialization rights;
Product liability or controlled-substance litigation, which does not necessarily affect patent validity.

A settlement could permit an authorized generic, delayed generic entry, or a license limited to non-infringing indications. None of those outcomes follows from the claim language alone.

What licensing deals affect US 10,016,407?

Numbrino commercialization has historically involved NRL Pharma and Lannett Company. FDA labeling identifies the product sponsor and manufacturer, while corporate filings and transaction documents determine the contractual allocation of patent rights, marketing rights, and enforcement authority. [2], [6]

A commercial license does not itself change patent scope. Its importance is economic: the party controlling the patent prosecution and enforcement rights may differ from the party selling the product. Any diligence should confirm whether the relevant agreement includes:

Exclusive US rights;
Patent enforcement authority;
Sublicensing rights;
Royalty obligations;
Bankruptcy termination rights;
Rights to settle ANDA litigation;
Rights to launch an authorized generic.

Is there biosimilar risk?

No conventional biosimilar pathway applies. Cocaine hydrochloride is a small-molecule active ingredient, so competitive entry would proceed through an ANDA or, in some cases, a 505(b)(2) application rather than a biosimilar application under the Public Health Service Act.

The principal competitive risks are therefore generic formulation duplication, a 505(b)(2) product with modified administration, and label-based design-around strategies. [4], [5]

Key Takeaways

US 10,016,407 is a method-of-use patent, not a broad composition patent.
The claims target near-4% cocaine hydrochloride nasal solutions used with pledgets before diagnostic or surgical procedures.
Hepatic and renal impairment are independent population branches.
Child-Pugh B, Child-Pugh C, and eGFR of approximately 15-29 mL/min/1.73 m² are expressly claimed dependent embodiments.
Claims 1-10 require sodium benzoate within approximately 0.07%-0.20%.
Claims 11-20 use a broader preservative limitation and require citric acid at approximately 0.01%-1.0%.
Claims 9 and 19 expressly cover nasal endoscopy.
The reported patent expiration date is June 8, 2035.
Numbrino's three-year FDA exclusivity has expired; the principal remaining protection is patent-based.
A copied product with a copied label presents the highest infringement risk.
A section viii carve-out, alternative delivery system, or formulation change may reduce risk, subject to claim construction and induced-infringement analysis.
No Paragraph IV litigation, settlement, or patent license can be established from the claims supplied.

FAQs About US Patent 10,016,407

Does US 10,016,407 cover all cocaine nasal sprays?

No. It requires a specific concentration range, ready-to-use formulation, pledget administration, nasal-mucosa contact, procedure-related use, and hepatic or renal impairment.

Can a generic avoid the patent by using a nasal spray device?

Potentially. A spray device may avoid the express pledget limitation, but the product labeling, instructions, and equivalents analysis would determine the litigation risk.

Does the patent require both hepatic and renal impairment?

No. The claims use "hepatic or renal impairment." Either condition can satisfy the population limitation.

Is sodium benzoate required in every claim?

No. Claims 1-10 require sodium benzoate in a defined range. Claim 11 requires a preservative but does not initially limit it to sodium benzoate. Claim 20 specifies sodium benzoate.

Does FDA approval of a generic automatically eliminate this patent risk?

No. FDA approval and patent clearance are separate issues. An ANDA applicant must address listed patents through the applicable certification or statement and may face patent litigation before launch.

References

United States Patent and Trademark Office. (2018). US Patent No. 10,016,407, methods of administering cocaine hydrochloride nasal solution to subjects with hepatic or renal impairment. https://patents.google.com/patent/US10016407B2/en
U.S. Food and Drug Administration. (2018). Numbrino: Cocaine hydrochloride nasal solution prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications. In Regulatory procedures manual. https://www.fda.gov/
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
Lannett Company, Inc. (2017). Annual report and product commercialization disclosures. U.S. Securities and Exchange Commission. https://www.sec.gov/edgar/browse//?CIK=836532

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lxo Ireland	GOPRELTO	cocaine hydrochloride	SOLUTION;NASAL	209963-001	Dec 14, 2017		RX	Yes	Yes	10,016,407	⤷ Start Trial				METHOD OF ADMINISTERING A LOCAL ANESTHETIC PRIOR TO PERFORMING A DIAGNOSTIC OR SURGICAL PROCEDURE ON A SUBJECT WITH HEPATIC OR RENAL IMPAIRMENT	⤷ Start Trial
Omnivium Pharms	NUMBRINO	cocaine hydrochloride	SOLUTION;NASAL	209575-001	Jan 10, 2020		RX	Yes	Yes	10,016,407	⤷ Start Trial				METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES IN PATIENTS WITH HEPATIC IMPAIRMENT	⤷ Start Trial
Omnivium Pharms	NUMBRINO	cocaine hydrochloride	SOLUTION;NASAL	209575-001	Jan 10, 2020		RX	Yes	Yes	10,016,407	⤷ Start Trial				METHOD OF ADMINISTERING A LOCAL ANESTHETIC TO THE MUCOUS MEMBRANES IN PATIENTS WITH RENAL IMPAIRMENT	⤷ Start Trial
Omnivium Pharms	NUMBRINO	cocaine hydrochloride	SOLUTION;NASAL	209575-001	Jan 10, 2020		RX	Yes	Yes	10,016,407	⤷ Start Trial				METHOD OF ADMINISTERING A LOCAL ANESTHETIC PRIOR TO PERFORMING A DIAGNOSTIC OR SURGICAL PROCEDURE ON A SUBJECT WITH HEPATIC OR RENAL IMPAIRMENT	⤷ 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: 10,016,407

Which drugs does patent 10,016,407 protect, and when does it expire?

Summary for Patent: 10,016,407