US Patent 9,636,408: Cyclobenzaprine Hydrochloride-Mannitol Eutectic Composition, Claim Scope, and Patent Landscape

US Patent 9,636,408 protects a narrowly defined pharmaceutical composition containing a cyclobenzaprine hydrochloride-mannitol eutectic and related manufacturing methods. The central limitation is a composition containing approximately 75% cyclobenzaprine hydrochloride and 25% mannitol, with a melting point of approximately 143°C. Dependent claims add selected basifying agents, including dipotassium hydrogen phosphate, disodium hydrogen phosphate, and trisodium citrate.

The patent is materially narrower than a patent covering cyclobenzaprine generally, a conventional cyclobenzaprine tablet, or mannitol as an excipient. Commercial risk turns on whether a competing product contains the claimed eutectic within the specified composition and melting-point ranges, or is made by the claimed mixing or milling process.

What does US Patent 9,636,408 protect?

The patent has six claims divided into two groups:

Claim group	Claims	Subject matter
Composition	1-3	Cyclobenzaprine hydrochloride-mannitol eutectic, with optional basifying agents
Manufacturing method	4-6	Mixing or milling the active ingredient and mannitol, with optional addition of a basifying agent

Claim 1 is the broadest claim. It requires all of the following:

A pharmaceutical composition.
A eutectic composition.
Mannitol at 25% ±2% by weight.
Cyclobenzaprine hydrochloride at 75% ±2% by weight.
A melting point of 143°C ±3°C.

The operative numerical ranges are:

Component or property	Claimed target	Numerical range
Mannitol	25 wt%	23-27 wt%
Cyclobenzaprine hydrochloride	75 wt%	73-77 wt%
Eutectic melting point	143°C	140-146°C

The claim uses “comprising,” an open-ended transitional term. A product may therefore contain additional excipients, coatings, binders, lubricants, disintegrants, solvents, or other ingredients and still fall within claim 1 if the required eutectic and numerical limitations are present.

How should the eutectic limitation in claim 1 be interpreted?

The eutectic limitation is the principal technical and infringement issue. A simple physical mixture of cyclobenzaprine hydrochloride and mannitol should not automatically satisfy the claim. The composition must be characterized as a eutectic and must melt within the claimed 140°C to 146°C range.

A likely claim analysis would examine:

Differential scanning calorimetry, or DSC.
Melting-endotherm location.
X-ray powder diffraction.
Thermal behavior after processing.
Component ratios.
Whether the product retains the claimed solid-state form after tableting, granulation, coating, or storage.

The claim does not state the DSC heating rate, sample preparation, atmospheric conditions, instrument calibration, or method for determining the melting point. Those omissions may create disputes over test reproducibility. They do not necessarily invalidate the claim, but they increase the importance of expert testing and claim-construction evidence.

The term “eutectic composition” can also create a boundary issue. A composition may show a depressed melting point without being a single crystalline phase or a formally characterized eutectic. In a dispute, the patent holder would likely rely on the claimed ratio and thermal transition together. An accused party would likely contest whether its formulation has the same thermal event or only exhibits ordinary excipient-active interactions.

What are the scope and limitations of claims 2 and 3?

Claim 2 narrows claim 1 by requiring a basifying agent. Claim 3 further limits the basifying agent to one of three listed substances:

K2HPO4, dipotassium hydrogen phosphate;
Na2HPO4, disodium hydrogen phosphate; or
Trisodium citrate.

These claims do not cover every alkaline or pH-adjusting excipient. A formulation using potassium carbonate, sodium carbonate, magnesium oxide, tromethamine, sodium bicarbonate, or another base would not literally satisfy claim 3 unless the listed agent is also present.

The claims do not specify:

The quantity of basifying agent;
Its particle size;
Its location in the dosage form;
The pH of the final product;
Whether the agent must be incorporated before or after eutectic formation;
Whether the agent must affect dissolution, stability, or bioavailability.

A product containing one of the listed agents in a minor amount could therefore present literal infringement risk if the other limitations are met. The absence of a minimum quantity may create a de minimis and claim-construction issue, but it does not eliminate the limitation.

What manufacturing methods are protected by claims 4 to 6?

Claim 4 covers a method of manufacturing the claim 1 composition by “mixing or milling” a composition containing the claimed proportions of mannitol and cyclobenzaprine hydrochloride.

The method claim is broad in process terms. It does not require:

A particular mill;
A defined milling speed;
A specified milling duration;
Wet or dry processing;
A solvent;
Heating or cooling;
A particular particle-size distribution;
A defined order of addition;
A granulation step.

A competitor using dry blending, ball milling, jet milling, high-shear mixing, planetary mixing, or another process could face claim 4 exposure if the process produces the claimed composition and the required ingredients are present in the specified ranges.

Claims 5 and 6 add the basifying-agent limitation. Claim 6 is limited to the three specified agents. The process claims may be important where the final dosage form is difficult to characterize, but manufacturing records, batch records, process validation documents, and discovery evidence can establish whether mixing or milling occurred.

How strong is the patent estate for cyclobenzaprine hydrochloride?

The patent estate reflected by the supplied claims is technically focused rather than molecule-wide.

Patent subject	Apparent coverage under US 9,636,408	Competitive significance
Cyclobenzaprine hydrochloride as an active ingredient	No standalone protection	Low
Conventional cyclobenzaprine tablet	Not necessarily covered	Low unless it contains the eutectic
Mannitol-containing formulation	Only within the claimed ratio and eutectic limitations	Moderate
Eutectic cyclobenzaprine-mannitol composition	Core protection	High
Basified eutectic composition	Narrower dependent-claim protection	Moderate to high
Manufacturing by mixing or milling	Process protection	Moderate
New cyclobenzaprine indication	Not covered by the supplied claims	None
Extended-release technology	Not covered by the supplied claims	None
Transdermal or injectable delivery	Not covered by the supplied claims	None

The patent does not, based on the supplied claims, cover cyclobenzaprine free base, every cyclobenzaprine salt, all cyclobenzaprine dosage forms, or all combinations with mannitol. It also does not claim a specific therapeutic indication.

When does US Patent 9,636,408 lose exclusivity?

The patent was issued on May 2, 2017. The enforceable term is generally calculated from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any relevant priority or prosecution history. The grant date alone does not establish the expiration date.[1]

The patent record should be reviewed for:

Earliest effective nonprovisional filing date;
Patent-term adjustment;
Terminal disclaimer;
Continuation or divisional relationships;
Patent-term extension;
Reexamination or post-grant proceedings;
Maintenance-fee status.

A patent expiration date cannot be calculated reliably from the grant number and grant date alone. The USPTO Patent Center record and the patent’s term information control the analysis.[2]

What is the Orange Book status of US 9,636,408?

A patent is not automatically listed in the FDA Orange Book because it claims a pharmaceutical composition. Orange Book listing depends on whether the patent is submitted for an approved drug product and whether it meets FDA listing criteria for an NDA product.[3]

The supplied claims could potentially be relevant to an NDA product containing:

Cyclobenzaprine hydrochloride;
Mannitol;
The claimed eutectic;
One of the listed basifying agents.

The claims do not establish that the patent is listed in the Orange Book. They also do not establish that the patent is associated with Flexeril, Amrix, Fexmid, or a particular approved cyclobenzaprine product. Orange Book status must be determined from the FDA’s current patent and exclusivity listings, not from the patent claims alone.

What Paragraph IV challenges could target this patent?

An ANDA applicant could challenge the patent through a Paragraph IV certification if the patent is listed for the reference product and the applicant believes it is invalid, not infringed, or not enforceable.[4]

Potential Paragraph IV positions include:

Noninfringement

A generic applicant could design around one or more critical limitations by using:

A different mannitol concentration;
A different cyclobenzaprine hydrochloride concentration;
A non-eutectic physical mixture;
A melting transition outside 140°C to 146°C;
A different excipient instead of the listed basifying agents;
A manufacturing process that does not involve mixing or milling within the claimed composition parameters.

Invalidity

Potential validity attacks would likely focus on:

Anticipation by an earlier cyclobenzaprine-mannitol composition;
Obviousness based on cyclobenzaprine formulations and mannitol excipient disclosures;
Lack of written description for the claimed eutectic or broad process language;
Enablement across the full numerical ranges;
Indefiniteness of “eutectic composition” or the melting-point measurement.

The narrow numerical ranges may help distinguish earlier broad disclosures, but an obviousness challenge could argue that routine formulation optimization would have identified the claimed ratio and thermal behavior.

Inherency

A patent holder could argue that a competing formulation inherently forms the claimed eutectic even if the ANDA does not expressly identify one. This makes comparative solid-state testing important. A noninfringement position based solely on the absence of the word “eutectic” in product documentation may be insufficient.

What generic launch risks exist?

Generic launch risk depends on whether the reference product and the proposed generic contain the claimed solid-state composition. The principal scenarios are:

Launch scenario	Risk under composition claims	Risk under process claims
Cyclobenzaprine product without mannitol	Low	Low
Mannitol formulation outside 23-27 wt%	Lower, subject to equivalents	Potentially low
Physical mixture without claimed eutectic	Moderate factual risk	Depends on process
Eutectic within 140-146°C	High	High if made by mixing or milling
Listed basifying agent present	Higher under claims 2-3	Higher under claims 5-6
Alternative base used	Lower under claim 3	Lower under claim 6
Different manufacturing process	No effect on claims 1-3	Potentially reduces process-claim risk

The highest-risk product is one that reproduces the 75:25 cyclobenzaprine hydrochloride-mannitol ratio, demonstrates a melting point between 140°C and 146°C, and includes one of the three listed basifying agents.

What patent litigation or settlement agreements affect this patent?

The supplied claim language does not establish litigation, a Paragraph IV notice, a settlement agreement, or a license. Those events are separate from the patent record and must be verified through PACER, FDA listing records, ANDA litigation filings, and SEC disclosures where applicable.

A litigation review should search for:

District-court cases naming the patent;
Hatch-Waxman complaints filed within 45 days of a Paragraph IV notice;
Declaratory-judgment actions;
Claim-construction orders;
Preliminary-injunction proceedings;
Settlement agreements involving launch dates or licenses;
PTAB inter partes review or post-grant review proceedings.

A patent number alone does not prove that a patent is being asserted against a particular generic manufacturer.

Which companies are competing in cyclobenzaprine products?

Cyclobenzaprine has historically been marketed in immediate-release and extended-release products. Relevant commercial categories include:

Category	Typical product type	Patent relevance
Immediate-release cyclobenzaprine	Tablets and capsules	Usually separate from the eutectic claim unless the formulation matches
Extended-release cyclobenzaprine	Once-daily capsules	Requires separate release-profile and formulation analysis
Authorized generic	NDA-linked generic product	May inherit NDA patent exposure
ANDA generic	Immediate-release or other approved dosage form	Paragraph IV and formulation design-around risk
Novel dosage form	ODT, liquid, multiparticulate, or specialty formulation	May involve separate formulation patents

The presence of generic cyclobenzaprine products does not demonstrate freedom to operate against US 9,636,408. Generic approval, patent listing, and actual infringement are separate questions.

What manufacturing and IP barriers does the patent create?

The strongest practical barrier is not the ingredient combination alone. It is the requirement to reproduce a specific solid-state composition with a defined thermal profile.

A competitor may need to control:

Raw-material polymorph and hydrate state;
Cyclobenzaprine hydrochloride particle properties;
Mannitol grade and crystallinity;
Mixing or milling energy;
Moisture exposure;
Thermal history;
Basifying-agent incorporation;
Post-compression solid-state stability.

A product that initially falls outside the claim may move into the claim range during storage or processing. Conversely, a product that forms the eutectic during milling may lose that structure during granulation or tableting. Stability testing should therefore include solid-state characterization at release and throughout the proposed shelf life.

How does US 9,636,408 compare with conventional cyclobenzaprine patents?

US 9,636,408 is narrower than patents claiming the active ingredient, a broad dosage form, or a therapeutic use. Its value depends on the commercial importance of the protected eutectic and the difficulty of designing around the ratio and melting-point limitations.

Patent type	Scope	Design-around potential
Active-ingredient patent	Broad molecule-level protection	Usually limited before expiry
Method-of-use patent	Indication or dosing regimen	Moderate
Release-profile patent	Extended-release performance	Moderate to high
Formulation patent	Specific excipients and ratios	Often high
Eutectic solid-state patent	Specific composition and thermal behavior	Moderate, but testing-intensive
Manufacturing patent	Defined preparation process	Often high unless process is commercially necessary

Key Takeaways

Claim 1 is limited to a cyclobenzaprine hydrochloride-mannitol eutectic containing approximately 73-77 wt% cyclobenzaprine hydrochloride and 23-27 wt% mannitol.
The eutectic must melt at approximately 140°C to 146°C.
Claims 2 and 3 cover the same composition with selected basifying agents, especially K2HPO4, Na2HPO4, and trisodium citrate.
Claims 4-6 cover mixing or milling methods and are not limited to a particular machine, speed, duration, or solvent.
The patent does not, on the supplied claims, cover cyclobenzaprine generally, all mannitol formulations, all extended-release products, or therapeutic uses.
DSC and related solid-state testing are central to infringement and validity analysis.
Orange Book listing, patent expiration, litigation, licensing, and settlement status cannot be inferred from the claim text or grant number alone.
The most credible design-around strategies are changing the composition ratio, avoiding formation of the claimed eutectic, using a different basifying agent, or adopting a manufacturing process outside claims 4-6.

FAQs

Does a cyclobenzaprine tablet with mannitol automatically infringe US 9,636,408?

No. The product must satisfy the claimed composition, eutectic, percentage, and melting-point limitations. Mannitol alone is insufficient.

Can a formulation avoid claim 3 by using sodium bicarbonate?

Potentially. Sodium bicarbonate is not one of the three basifying agents expressly listed in claim 3. The formulation would still need to be assessed under claim 1 and under the doctrine of equivalents.

Is the 75:25 ratio measured before or after adding other excipients?

The claims specify the weight percentages of mannitol and cyclobenzaprine hydrochloride, but do not expressly state whether the calculation is based on the active-eutectic fraction or the total finished dosage form. That issue may require claim construction and technical evidence.

Can a competitor avoid the process claims by using direct compression?

Possibly. Direct compression may avoid a process claim requiring mixing or milling, but the final product could still infringe claims 1-3 if it contains the claimed eutectic.

Does the melting point have to be exactly 143°C?

No. The stated tolerance creates a claimed range of approximately 140°C to 146°C, subject to the applicable measurement method and claim construction.

References

United States Patent and Trademark Office. (2017). U.S. Patent No. 9,636,408.
United States Patent and Trademark Office. (n.d.). Patent Center: Patent term and prosecution records.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). ANDA submissions: Patent certifications and the Hatch-Waxman framework.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Tonix	TONMYA	cyclobenzaprine hydrochloride	TABLET;SUBLINGUAL	219428-001	Aug 15, 2025		RX	Yes	Yes	9,636,408	⤷ 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
Australia	2014233277	⤷ Start Trial
Brazil	112015022095	⤷ Start Trial
Canada	2904812	⤷ Start Trial
Canada	3119755	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,636,408

Which drugs does patent 9,636,408 protect, and when does it expire?

Summary for Patent: 9,636,408