US Patent 9,504,666: Chloroprocaine Intrathecal Use, Claim Scope and Patent Landscape

US Patent No. 9,504,666 protects a specific method of repeated intrathecal chloroprocaine administration. Its core limitations are a preservative- and antioxidant-free aqueous solution, pH 3.0 to 4.0, a daily dose of 15 to 80 mg, and repeated administration for two to 10 days. The narrower claims specify chloroprocaine hydrochloride, a 0.5% to 1.5% formulation, sodium chloride and hydrochloric acid, and combination use with adrenaline or analgesics.

The patent is a use patent, not a broad composition patent. It does not cover every chloroprocaine injection, every spinal-anesthesia procedure, or every preservative-free chloroprocaine product. Infringement requires practice of the claimed intrathecal dosing regimen and, for the narrower claims, the specified formulation or combination therapy.

What does US Patent 9,504,666 cover?

The patent covers a method of central local anesthesia using repeated intrathecal chloroprocaine administration. Claim 1 is the independent claim and establishes the principal scope:

Claim limitation	Requirement
Medical use	Central loco-anesthesia
Route	Intrathecal administration
Active ingredient	Chloroprocaine or a salt
Dosage form	Injectable pharmaceutical aqueous solution
Excipients	Free of preservatives and/or antioxidants
pH	3.0 to 4.0
Daily dose	15 to 80 mg per day
Duration	Daily administration repeated for two to 10 days

The claim is cumulative. A competing product or treatment must satisfy each limitation to fall within the literal scope of claim 1.

The patent’s commercial relevance depends on whether a product label, physician instructions, hospital protocol, or actual use directs the claimed repeated-dosing regimen. A single-dose spinal anesthetic procedure would not satisfy the repeated-administration limitation.

What are the dependent claims in US 9,504,666?

Claims 2 through 9 narrow claim 1. They do not create independent protection outside the limitations of claim 1.

Claim	Additional limitation
2	Daily dose of 30 to 60 mg
3	Administration with adrenaline and/or an analgesic drug
4	Chloroprocaine salt is chloroprocaine hydrochloride
5	Daily administration repeated for three to seven days
6	Solution contains chloroprocaine HCl, sodium chloride, sterile water and hydrochloric acid
7	Chloroprocaine concentration is 0.5% to 1.5% by weight
8	5 to 15 mg chloroprocaine HCl per mL of water, 4 to 12 mg sodium chloride, and hydrochloric acid sufficient to achieve pH 3.0 to 4.0
9	The analgesic is acetaminophen, an NSAID, corticosteroid or opioid

Claim 8 is the most formulation-specific claim. It describes a low-pH, isotonic or near-isotonic aqueous chloroprocaine hydrochloride solution using sodium chloride and hydrochloric acid. The claim does not require a particular commercial container, syringe, vial, preservative system or manufacturing process.

What is the technical scope of the patent?

Intrathecal administration is the central limitation

The patent is directed to administration into the intrathecal space, generally through spinal or neuraxial injection. Intravenous, intramuscular, subcutaneous, epidural and topical administration would not satisfy the route limitation.

The wording "central loco-anesthesia" may create claim-construction issues because it is less precise than "spinal anesthesia." The more objective limitations are the route, solution characteristics, dose and repeated administration.

The repeated-treatment requirement limits the claim

Claim 1 requires administration daily for two to 10 days. Claim 5 narrows that period to three to seven days. A regimen involving only one spinal injection, even if it uses the same solution and dose, falls outside these claims.

This limitation materially reduces the patent’s reach over conventional short-duration spinal anesthesia. Standard spinal anesthesia often involves one administration before surgery. The patented regimen is directed to repeated intrathecal treatment rather than a single perioperative injection.

The solution must be free of preservatives and antioxidants

The claim requires a solution that is "preservatives and/or antioxidant free." The wording may be interpreted as requiring the absence of preservatives, antioxidants, or both, depending on the construction applied to the phrase. A formulation containing a preservative or antioxidant presents a potential non-infringement position, although the commercial and regulatory suitability of such an excipient would require separate analysis.

Claim 6 identifies a formulation containing:

Chloroprocaine hydrochloride;
Sodium chloride;
Sterile water; and
Hydrochloric acid.

Claim 8 provides concentration ranges for chloroprocaine HCl and sodium chloride and requires hydrochloric acid sufficient to produce a pH of 3.0 to 4.0.

Claim 7 covers a concentration range, not one commercial strength

The 0.5% to 1.5% weight range is broad enough to encompass 0.5%, 1.0% and 1.5% solutions, subject to the other limitations. A product outside that concentration range could still fall within claim 1 if it meets the broader dosage and regimen requirements.

What are the patent dates and expiration implications?

The patent was issued on November 29, 2016. The underlying family claims priority to a 2009 filing date, with a PCT or nonprovisional filing occurring in 2010. The ordinary US patent term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and patent-term extension rules.[1]

Event	Date or status
Earliest family priority	December 18, 2009
PCT or international filing period	December 2010
US patent grant	November 29, 2016
Patent number	US 9,504,666 B2
Expected ordinary expiration framework	December 2030, subject to adjustment
Patent type	Method-of-use patent
Patent-term extension	No verified extension should be assumed without a current USPTO or Orange Book record

The priority date does not necessarily determine the expiration date. For US term calculations, the relevant date is generally the earliest effective US nonprovisional or international application filing date, not a provisional priority filing by itself.[1]

A current USPTO Patent Center record and the FDA Orange Book should control any transaction, launch or litigation decision involving the live term.

What is the Orange Book status of US Patent 9,504,666?

The patent is associated with chloroprocaine hydrochloride spinal-anesthesia products, including the Clorotekal product family. FDA Orange Book treatment depends on the approved product, NDA holder, listed patent and use code. A method patent may be listed when it claims an approved method of using the drug under FDA listing rules.[2]

The patent’s commercial impact therefore depends on four questions:

Whether US 9,504,666 is currently listed for the relevant chloroprocaine product.
Whether the listed use code covers the proposed generic’s labeling.
Whether the generic applicant files a Paragraph IV certification.
Whether the patent holder brings suit within the statutory litigation window.

An Orange Book listing does not by itself prove infringement. It creates a statutory framework for an ANDA applicant’s patent certification and can trigger patent litigation after a Paragraph IV notice.[3]

When does chloroprocaine lose patent and regulatory exclusivity?

Patent expiration and FDA regulatory exclusivity are separate events.

Patent exclusivity

The patent’s ordinary term is expected to extend into December 2030, subject to the official term calculation. A generic applicant could seek approval before that date through an ANDA containing a Paragraph IV certification or a section viii statement, depending on the listed use and the proposed label.

FDA exclusivity

Chloroprocaine is an established local anesthetic. Its active ingredient has been used for decades, so the relevant FDA exclusivity would generally attach to the specific approved product or application rather than to the molecule broadly.

For an NDA-approved product, possible exclusivity categories include:

New chemical entity exclusivity, if applicable;
Three-year exclusivity for a qualifying new clinical investigation;
Orphan-drug exclusivity, if the product qualifies for an orphan indication.

A generic chloroprocaine applicant does not face a biosimilar pathway. Chloroprocaine hydrochloride is a small-molecule drug and is regulated through the ANDA framework when the reference product and pharmaceutical equivalence requirements support that pathway.

What Paragraph IV challenges affect US Patent 9,504,666?

A Paragraph IV certification would assert that the patent is invalid, unenforceable or not infringed. For this patent, likely challenge theories would focus on claim construction, written description, enablement, obviousness and the distinction between the patented repeated regimen and conventional single-dose spinal anesthesia.

Potential non-infringement positions include:

Single-dose rather than repeated intrathecal administration;
A daily dose below 15 mg or above 80 mg;
A treatment period outside two to 10 days;
A route other than intrathecal administration;
A formulation containing a preservative or antioxidant;
A pH outside 3.0 to 4.0;
A chloroprocaine concentration outside claim 7, where claim 7 is asserted;
Absence of the specified combination drug for claims 3 and 9;
Absence of sodium chloride or hydrochloric acid for claims 6 and 8.

Potential invalidity arguments include:

Obviousness based on earlier spinal-anesthesia disclosures combined with known preservative-free chloroprocaine formulations;
Lack of written description for the full combination of dose, pH, formulation and repeated administration;
Enablement challenges directed to the breadth of the treatment regimen;
Indefiniteness concerns involving "central loco-anesthesia" or the phrase "preservatives and/or antioxidant free";
Anticipation by an earlier publication that discloses all limitations in combination.

No reliable commercial conclusion should be drawn from the mere absence of a publicly visible lawsuit. Paragraph IV activity may be tied to a specific ANDA, product label and Orange Book use code.

What patent litigation affects chloroprocaine?

The principal litigation risk is an ANDA patent case under 35 U.S.C. §271(e)(2), assuming the patent is listed against an approved reference product and a generic applicant submits a Paragraph IV certification.[3]

A litigation analysis should separate:

Issue	Business effect
Patent listed in Orange Book	Creates an ANDA certification pathway
Paragraph IV notice	May trigger a 45-day period for suit
Timely patent suit	Can impose a 30-month FDA approval stay, subject to statutory exceptions
Claim construction	Determines whether a proposed label practices the repeated regimen
Settlement	May establish a negotiated generic launch date
Patent invalidity or non-infringement	Can remove or reduce the launch barrier
Section viii carve-out	May avoid infringement if the patented method can be omitted from labeling

A section viii strategy is more plausible if the protected regimen is not required for the generic label or if the generic seeks approval only for an unclaimed single-dose spinal-anesthesia use. The feasibility depends on FDA labeling, the Orange Book use code and whether the carved-out label would still encourage the patented method.

How strong is the patent estate for chloroprocaine?

The strength of US 9,504,666 is concentrated rather than broad.

Strengths

It combines multiple objective limitations: intrathecal route, low-pH aqueous solution, preservative-free status, dose and duration.
The formulation claims identify specific excipients and concentration ranges.
The claims may cover a repeated-use protocol that is distinct from ordinary single-dose spinal anesthesia.
Claim 1 has several potential infringement hooks if a product label expressly directs the regimen.

Weaknesses

The patent does not claim chloroprocaine as a molecule.
It does not broadly claim every chloroprocaine injection or every spinal-anesthesia use.
The two-to-10-day repeated regimen may be absent from conventional product labels.
The phrase "central loco-anesthesia" may create interpretive uncertainty.
The formulation claims are narrower than the independent method claim.
A generic applicant may pursue a single-dose or carved-out indication that avoids the repeated regimen.

The estate is therefore more valuable as an indication and regimen barrier than as a general product barrier.

What formulations are protected by the patent?

The most relevant formulation is an aqueous chloroprocaine hydrochloride solution with acidic pH and no preservative or antioxidant. Claim 8 gives the narrowest quantitative description.

Formulation characteristic	Claim requirement
Chloroprocaine form	Chloroprocaine HCl
Chloroprocaine concentration	5 to 15 mg/mL of water
Approximate weight concentration	0.5% to 1.5% by weight under claim 7
Sodium chloride	4 to 12 mg
pH control	Hydrochloric acid sufficient for pH 3.0 to 4.0
Vehicle	Sterile water
Preservatives	Excluded
Antioxidants	Excluded under the claim language

A formulation matching these parameters is not automatically infringing. The formulation must be used in the claimed intrathecal, repeated-dosing method. Conversely, a formulation outside claim 8 may still fall within claim 1.

How does US 9,504,666 compare with competing chloroprocaine products?

The principal distinction is between a patented repeated-use method and conventional single-dose spinal anesthesia.

Attribute	US 9,504,666 regimen	Conventional chloroprocaine spinal use
Route	Intrathecal	Usually intrathecal
Dose	15 to 80 mg daily	Often procedure-specific single dose
Administration	Repeated for two to 10 days	Generally one administration
pH	3.0 to 4.0	Product-specific
Preservatives	Excluded	Product-specific
Commercial barrier	Method patent	May depend on product, formulation or label
Generic strategy	Must address repeated-use claims	May pursue single-dose labeling

Clorotekal is a short-acting chloroprocaine hydrochloride spinal-anesthesia product. Its approved use and label should be compared directly with the patent’s repeated daily regimen. A mismatch between the FDA-approved indication and the patent claims can materially affect Orange Book relevance, ANDA certification strategy and litigation exposure.[4]

What licensing deals and ownership issues are relevant?

The patent is associated with the Sintetica chloroprocaine product platform. Ownership, assignment and licensing should be confirmed through USPTO assignment records and the relevant commercial agreements. A patent assignment does not necessarily disclose a product license, co-promotion arrangement or royalty agreement.

For diligence, the relevant ownership questions are:

Whether the patent was assigned from the original applicant to Sintetica or an affiliate;
Whether the Orange Book-listed NDA holder owns the patent;
Whether an exclusive license covers US enforcement rights;
Whether settlement or license agreements govern generic entry;
Whether any terminal disclaimer or continuation patent affects the estate.

Public patent records establish recorded ownership, not the full economic terms of private licensing arrangements.

What generic launch risks exist?

The likely launch scenarios are:

Scenario 1: Pre-expiration Paragraph IV launch

A generic applicant challenges the patent and prevails, obtains a settlement date, or launches at risk after litigation developments. This scenario creates the greatest near-term erosion risk.

Scenario 2: Section viii carve-out

The applicant omits the patented repeated regimen from its label and seeks approval for non-infringing uses, such as single-dose spinal anesthesia. This is the most important design-around path if FDA permits the carve-out.

Scenario 3: Post-expiration launch

The applicant waits until patent expiration. This reduces litigation risk but delays market entry and may allow the reference sponsor to retain commercial share until the end of the patent term.

Scenario 4: Label-driven infringement dispute

The proposed generic label does not expressly reproduce the patented regimen, but marketing, dosing instructions or physician use allegedly encourage it. The dispute would turn on induced infringement and the relationship between the label and actual use.

What manufacturing and geographic barriers remain?

US 9,504,666 does not claim a manufacturing process. A manufacturer could potentially produce a chloroprocaine solution without infringing the patent if it does not practice or induce the claimed intrathecal regimen.

Manufacturing risks arise from separate requirements:

Sterile injectable production;
Aseptic processing;
Container-closure integrity;
Low-pH formulation stability;
Control of impurities and degradation products;
Sodium chloride and hydrochloric acid tolerances;
FDA current good manufacturing practice compliance;
ANDA pharmaceutical equivalence and bioequivalence requirements.

The patent is territorial. US claims do not directly prevent manufacturing, sale or use outside the United States. Foreign family members must be analyzed separately by jurisdiction, including their grant status, claim scope, term and national-phase prosecution history.

Key Takeaways

US 9,504,666 is a narrow-to-moderate scope method patent for repeated intrathecal chloroprocaine administration.
Claim 1 requires a preservative- and antioxidant-free aqueous solution, pH 3.0 to 4.0, 15 to 80 mg daily, and administration for two to 10 days.
Claims 6 through 8 add a specific chloroprocaine HCl, sodium chloride, sterile water and hydrochloric acid formulation.
The patent does not broadly cover chloroprocaine, all spinal anesthesia or single-dose intrathecal use.
The expected patent term extends into December 2030, subject to the official USPTO term calculation.
Paragraph IV and section viii strategies are the key generic-entry pathways.
The most credible design-around is a single-dose spinal-anesthesia label that omits the repeated two-to-10-day regimen.
Biosimilar risk is not relevant because chloroprocaine is a small-molecule drug.
The patent’s value is concentrated in method-of-use and regimen control, not manufacturing or composition exclusivity.

FAQs

Is US Patent 9,504,666 a composition patent?

No. It is a method-of-use patent. The formulation limitations narrow the claimed method but do not independently create a broad composition claim.

Does a single intrathecal chloroprocaine injection infringe the patent?

Generally, not claim 1, because the claim requires daily administration repeated for two to 10 days. Other patents or claims would need separate review.

Does the patent cover chloroprocaine without hydrochloride?

Claim 1 covers chloroprocaine or its salts. Claim 4 narrows the salt to chloroprocaine hydrochloride. A non-HCl salt could remain within claim 1 if all other limitations are met.

Can a generic applicant omit the patented indication?

Potentially. A section viii carve-out may be available if the patented repeated regimen can be removed from the proposed labeling without preventing approval for non-infringing uses.

Is Clorotekal protected by a biosimilar patent strategy?

No. Clorotekal contains chloroprocaine hydrochloride, a small-molecule active ingredient. Generic-drug and Orange Book mechanisms, rather than biosimilar mechanisms, govern the principal US competition pathway.

References

United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance. https://www.uspto.gov/patents/laws/patent-term-adjustment
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
United States Code. (2024). 35 U.S.C. § 271(e): Infringement of patents in regulated drug approvals. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section271
U.S. Food and Drug Administration. (2015). Clorotekal (chloroprocaine hydrochloride) injection prescribing information. https://www.accessdata.fda.gov/drugsatfda/
United States Patent and Trademark Office. (2016). US Patent No. 9,504,666 B2. https://patents.google.com/patent/US9504666B2/en

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
B Braun Medical	CLOROTEKAL	chloroprocaine hydrochloride	SOLUTION;INTRATHECAL	208791-001	Sep 26, 2017		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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	MI2012A2120	Dec 12, 2012

PCT Information
PCT Filed	December 11, 2013	PCT Application Number:	PCT/IB2013/060801
PCT Publication Date:	June 19, 2014	PCT Publication Number:	WO2014/091420

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	099443	⤷ Start Trial
Australia	2013356855	⤷ Start Trial
China	105283222	⤷ Start Trial
Israel	239270	⤷ Start Trial
Italy	MI20122120	⤷ Start Trial
South Korea	102162587	⤷ Start Trial
South Korea	20150085131	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,504,666