Details for Patent: 9,382,191

Which drugs does patent 9,382,191 protect, and when does it expire?

Patent 9,382,191 protects VALCHLOR and is included in one NDA.

This patent has forty-eight patent family members in twenty countries.

Summary for Patent: 9,382,191

Title:	Stabilized compositions of volatile alkylating agents and methods of using thereof
Abstract:	A composition and method for treatment of cancer. The composition for treating a skin disorder, comprising: a Nitrogen Mustard or an HX salt of the Nitrogen Mustard, wherein the Nitrogen Mustard or the HX salt of the Nitrogen Mustard is in a non-aqueous vehicle or carrier that does not include petrolatum or ethanol, wherein the non-aqueous vehicle or carrier that does not include petrolatum or ethanol does not include petrolatum or ethanol. The method comprises topically applying the composition of a Nitrogen Mustard or a HX salt of the Nitrogen Mustard to the affected skin, wherein the Nitrogen Mustard or the HX salt of the Nitrogen Mustard is in a non-aqueous vehicle or carrier that does not include petrolatum or ethanol, wherein the non-aqueous vehicle or carrier does not include petrolatum or ethanol.
Inventor(s):	Robert Alonso, Peter A. Crooks, Mark A. Pimley
Assignee:	Helsinn Birex Pharmaceuticals Ltd
Application Number:	US14/153,914
Patent Claim Types: see list of patent claims	Composition; Compound;

United States Drug Patent 9,382,191: Claims, Scope, Expiration, Orange Book Status, and Generic Risk

U.S. Patent No. 9,382,191 protects specific non-aqueous topical formulations of mechlorethamine, also known as bis-(2-chloroethyl)methylamine or nitrogen mustard. The patent is directed to the formulation vehicle rather than to mechlorethamine as a molecule or to the treatment of cutaneous lymphoma generally. Its central combination requires mechlorethamine at a minimum concentration, a diethylene glycol monoalkyl ether-type solvent, hydroxypropylcellulose, a specified stabilizer or preservative, and a secondary or tertiary alcohol. The patent issued July 5, 2016, and has a nominal expiration date of May 4, 2031, subject to any applicable patent-term adjustment.

The claims closely track the formulation architecture used for Valchlor, a mechlorethamine hydrochloride gel approved by the FDA for mycosis fungoides-type cutaneous T-cell lymphoma. The principal generic risk is therefore an ANDA applicant seeking to use a different vehicle, omit one required excipient category, or challenge validity and infringement under Paragraph IV.

What drug and formulation does U.S. Patent 9,382,191 protect?

U.S. Patent 9,382,191 protects a topical, non-aqueous composition containing mechlorethamine or a pharmaceutically acceptable salt, with defined excipient classes and concentration limits. The patent does not broadly cover every topical mechlorethamine product.

The claim structure is:

Claim element	Requirement
Active ingredient	Bis-(2-chloroethyl)methylamine or a pharmaceutically acceptable salt
Minimum active concentration	At least about 0.001% by weight
Vehicle	Non-aqueous
Express exclusions	No petrolatum and no ethanol
Glycol ether	HOCH2CH2OCH2CH2OR79, with R79 a linear C1-C6 alkyl
Cellulose polymer	Hydroxypropylcellulose
Preservative or stabilizer	BHT, benzyl alcohol, sodium benzoate, parabens, or edetate disodium
Alcohol	Secondary or tertiary alcohol containing 1-20 carbon atoms

The formula in claim 1 corresponds to a diethylene glycol monoalkyl ether. Claim 9 narrows R79 to ethyl, producing diethylene glycol monoethyl ether, commonly known as diethylene glycol monoethyl ether or Carbitol-type solvent. Claim 10 requires that solvent at 15% to 60% by weight.

Claim 18 is the most commercially important formulation claim. It requires:

• mechlorethamine hydrochloride;
• at least about 0.001% mechlorethamine salt;
• diethylene glycol monoethyl ether at 15% to 60%;
• hydroxypropylcellulose at no more than 5%;
• BHT at no more than 1%;
• edetate disodium at no more than 0.05%; and
• isopropyl alcohol at 1% to 20%.

The claim does not require every excipient appearing in the commercial product label. For example, propylene glycol and lactic acid are separately addressed in claims 15 and 16-17, but they are not required by claim 18.

How do the claims narrow from claim 1 to claim 18?

Claim 1 is an independent composition claim. Claims 2 through 17 add specific salt, solvent, alcohol, concentration, antioxidant, chelator, humectant, and acid limitations. Claim 18 is a fully specified combination claim.

Claim group	Technical limitation	Commercial relevance
Claims 1-5	Mechlorethamine salt, including HCl	Captures the active form used in Valchlor
Claims 6-8	Secondary or tertiary alcohol; preferably isopropanol; 1%-20%	Narrows the alcohol component
Claims 9-10	Ethyl-substituted glycol ether at 15%-60%	Targets the principal solvent system
Claims 11-13	HPC, BHT, and edetate disodium limits	Controls viscosity and chemical stability
Claim 14	Menthol at no more than 1%	Optional sensory or formulation component
Claims 15-17	Propylene glycol and organic acid, including lactic acid	Adds formulation and pH-related limitations
Claim 18	Combined HCl, glycol ether, HPC, BHT, edetate, and isopropanol formulation	Strongest direct read-through risk for the commercial formulation

Dependent claims inherit every limitation of the claims from which they depend. A product that falls within claim 18 necessarily falls within claim 1, assuming the claim terms are satisfied.

What is the scope of claim 1 of U.S. Patent 9,382,191?

Claim 1 has a combination scope. An accused product must generally contain each required element, either literally or under an applicable doctrine of equivalents.

The claim requires the presence of all four vehicle categories:

1. the specified glycol ether;
2. hydroxypropylcellulose;
3. at least one listed stabilizer or preservative; and
4. a secondary or tertiary alcohol.

The word “or” in the third category permits different formulation routes. A formulation can rely on BHT, benzyl alcohol, sodium benzoate, a paraben, or edetate disodium. It does not need to contain all five.

The claim also excludes petrolatum and ethanol from the non-aqueous vehicle or carrier. A product containing ethanol as a vehicle component presents a potential non-infringement position for the literal claim, although the significance of the exclusion would depend on the full formulation and claim construction.

The active ingredient threshold is low. At least about 0.001% by weight is required. This limitation captures products with concentrations materially below the 0.016% mechlorethamine concentration associated with Valchlor, provided the remaining formulation limitations are met.

The composition claims do not require:

• a particular disease indication;
• a particular tube, package, or applicator;
• a specific gel viscosity;
• a specific administration schedule;
• a particular patient population; or
• FDA approval.

The claims therefore operate primarily as formulation claims, not method-of-use or packaging claims.

What formulations are protected by claims 9, 10, and 18?

Claims 9 and 10 protect the ethyl member of the glycol ether genus. Claim 18 combines that solvent with the specific excipient architecture most closely associated with Valchlor.

A formulation containing the following composition would present a high literal infringement risk if the quantitative and compositional details were within the claimed ranges:

• mechlorethamine hydrochloride;
• diethylene glycol monoethyl ether;
• hydroxypropylcellulose;
• BHT;
• edetate disodium; and
• isopropyl alcohol.

The patent does not require a single fixed percentage for the active ingredient beyond the minimum threshold. This gives claim 18 broader concentration coverage than a claim limited to a specific commercial strength.

Claims 11-13 are narrower quantitative claims:

Claim	Limitation
11	Hydroxypropylcellulose at no more than 5%
12	BHT at no more than 1%
13	Edetate disodium at no more than 0.05%

A generic applicant could attempt to avoid these dependent claims by using concentrations above the stated upper limits, but that strategy would not necessarily avoid claim 1 or claim 18 unless the altered concentration also removed another required limitation or created a valid non-infringement position.

When does U.S. Patent 9,382,191 expire?

Event	Date
Earliest reported priority date	May 4, 2011
U.S. patent issuance	July 5, 2016
Nominal 20-year term endpoint	May 4, 2031
FDA approval of Valchlor	August 2013
Orphan-drug exclusivity endpoint	August 2020, subject to the applicable indication and exclusivity record

The patent’s nominal expiration is May 4, 2031, calculated from the earliest effective nonprovisional filing date reflected in the patent family. The enforceable term can differ if the patent received patent-term adjustment or is subject to a terminal disclaimer. The USPTO patent record controls the final term calculation. The patent was issued well after the 1995 transition to the modern U.S. patent-term regime, so the term is generally measured from the relevant nonprovisional filing date rather than from the issue date (U.S. Patent and Trademark Office, n.d.).

FDA regulatory exclusivity is separate from patent protection. Valchlor’s orphan-drug exclusivity did not extend through the patent’s 2031 expiration date. An ANDA applicant therefore faces a patent barrier even after FDA orphan exclusivity has expired.

What is the Orange Book status of U.S. Patent 9,382,191?

U.S. Patent 9,382,191 has been associated with Valchlor, the FDA-approved mechlorethamine hydrochloride topical gel. The Orange Book listing is commercially important because it can require an ANDA applicant to certify under Paragraph IV if the applicant seeks approval before the listed patent expires.

The Orange Book does not determine infringement or validity. It records patents submitted by the NDA holder and accepted for listing by FDA under the Hatch-Waxman framework. A listed formulation patent can support a 30-month stay if the NDA holder brings timely patent litigation after receiving a Paragraph IV notice, subject to statutory requirements (U.S. Food and Drug Administration, n.d.-a; 21 U.S.C. § 355).

The regulatory position should be separated into three categories:

Issue	Effect
FDA approval	Confirms the drug product and indication are approved
Orange Book listing	Creates a patent-certification and litigation framework for ANDA applicants
Patent expiration	Determines when the listed patent ceases to block launch, absent other enforceable rights

The patent listing does not automatically prevent a 505(b)(2) applicant from pursuing a different regulatory pathway, but that applicant would still need to address patent certification and any applicable use, formulation, or method-of-use patents.

Which companies are challenging U.S. Patent 9,382,191?

A Paragraph IV challenge cannot be inferred from the patent claims alone. A definitive assessment requires the FDA Orange Book, FDA Paragraph IV notice information where available, USPTO records, and federal court dockets.

The patent itself does not establish:

• that an ANDA has been filed;
• that a Paragraph IV certification has been delivered;
• that Actelion, Helsinn, or another rights holder filed an infringement action;
• that a settlement agreement exists; or
• that a generic launch date has been established.

For valuation purposes, the relevant competitive question is whether an ANDA applicant can design around the composition claims or invalidate them. A Paragraph IV certification would likely focus on obviousness, written description, enablement, claim construction, and the scope of prior art involving mechlorethamine stability in non-aqueous topical vehicles.

How strong is the patent estate for Valchlor?

The patent is strongest against products that copy the commercial formulation architecture. Claim 18 combines the active salt, glycol ether, polymer, antioxidant, chelator, and isopropanol. That combination can make a direct formulation copy commercially attractive but legally exposed.

The estate is weaker against a product that changes multiple formulation variables at once. Potential design-around categories include:

• replacing the diethylene glycol monoethyl ether with a different solvent;
• removing hydroxypropylcellulose and using another rheology modifier;
• replacing the listed preservative or stabilizer;
• using ethanol, if compatible with the product’s safety, stability, and regulatory profile;
• using a different alcohol class or no secondary or tertiary alcohol;
• changing from a non-aqueous to an aqueous or substantially different vehicle; or
• using a different salt or delivery format.

Each design-around has technical and regulatory consequences. Mechlorethamine is chemically reactive and formulation stability is a central development constraint. A vehicle that avoids literal infringement but produces degradation, inconsistent dosing, poor skin tolerability, or inadequate shelf life may not be commercially viable.

The patent’s practical strength therefore exceeds a simple element-by-element reading. The claims cover a solvent and excipient combination that appears selected to address stability and topical delivery. The same technical constraints that support the patent can make alternative formulations difficult to develop.

Does U.S. Patent 9,382,191 cover method of use, manufacturing, or biosimilar products?

The supplied claims are composition claims. They do not claim:

• treating mycosis fungoides;
• treating cutaneous T-cell lymphoma;
• a dosing regimen;
• a manufacturing process;
• a container or applicator;
• a stability-testing method; or
• a biologic or biosimilar product.

Because mechlorethamine is a small-molecule active, biosimilar risk is not the relevant competitive issue. The applicable pathway is generally an ANDA for a generic drug, or potentially a 505(b)(2) application for a product with formulation, dosage, or clinical differences.

A generic product could still face separate patents covering:

• topical treatment methods;
• specific gel or solvent systems;
• packaging;
• manufacturing controls;
• chemical intermediates;
• stability specifications; or
• other formulations in the same patent family.

Those rights must be analyzed separately from U.S. Patent 9,382,191.

What patent litigation and settlement risks affect generic entry?

A Paragraph IV certification can trigger patent litigation if the patent holder files suit within the statutory period. If litigation is filed, FDA approval may be stayed for up to 30 months, unless the court resolves the case earlier or the stay is modified.

The principal litigation issues would likely include:

1. Whether the accused formulation contains every element of claim 1 or claim 18.
2. Whether “non-aqueous vehicle or carrier” excludes formulations containing incidental water.
3. Whether the glycol ether is present in the claimed chemical form.
4. Whether one of the listed preservative or stabilizer categories is present.
5. Whether a concentration is within a claimed “at most,” “from,” or “at least about” range.
6. Whether the claims are obvious in view of prior art formulations.
7. Whether the specification adequately supports the full breadth of the claimed genus and concentration ranges.

A settlement could allow an authorized generic, a licensed generic, or a negotiated launch date before May 2031. No settlement terms should be assumed from the existence of the patent or from an Orange Book listing.

How does this patent compare with generic launch scenarios?

Scenario	Likely patent exposure	Commercial implication
Direct copy of Valchlor-type formulation	High	Strongest infringement risk under claims 1 and 18
Same active, different glycol ether	Reduced for claims 9, 10, and 18	Requires stability and bioequivalence support
Same solvent, different polymer	Reduced if HPC is absent	May affect viscosity and dosing uniformity
Ethanol-based formulation	Potentially outside express vehicle exclusion	Requires separate safety and stability assessment
Alternative salt or active form	Depends on pharmaceutical equivalence and claim coverage	Could create regulatory or clinical complications
505(b)(2) product with novel vehicle	Patent certification remains relevant	May face formulation and method patents
Product launched after May 4, 2031	This patent no longer blocks launch	Other listed or unlisted rights may remain

The highest-value generic strategy is likely a formulation design-around supported by a Paragraph IV invalidity or non-infringement position. A direct copy would reduce development risk but increase litigation exposure.

What is the geographic coverage of U.S. Patent 9,382,191?

The patent grants rights in the United States only. Foreign counterparts may protect related formulations in Europe, Canada, Japan, and other jurisdictions, but the U.S. patent does not itself establish foreign coverage.

A global launch assessment requires a country-by-country review of:

• issued counterpart patents;
• pending continuations or divisionals;
• national-phase applications;
• patent-term adjustments or supplementary protection certificates;
• local Orange Book equivalents;
• regulatory exclusivity; and
• local litigation or settlement records.

The U.S. patent’s expiration date cannot be imported into other jurisdictions without reviewing the corresponding family member.

Key Takeaways

• U.S. Patent 9,382,191 is a formulation patent for non-aqueous topical mechlorethamine compositions.
• Claim 1 requires mechlorethamine, a specified glycol ether, hydroxypropylcellulose, a listed preservative or stabilizer, and a secondary or tertiary alcohol.
• Claim 18 is the principal commercial claim because it specifies mechlorethamine hydrochloride, diethylene glycol monoethyl ether, HPC, BHT, edetate disodium, and isopropanol.
• Petrolatum and ethanol are expressly excluded from the claimed vehicle.
• The nominal patent expiration date is May 4, 2031, subject to USPTO term adjustment and any terminal disclaimer.
• Valchlor’s FDA regulatory exclusivity is separate from the patent term and did not extend through 2031.
• The patent creates substantial risk for a direct generic copy but leaves potential design-around paths involving the solvent, polymer, preservative, alcohol, or vehicle type.
• Biosimilar risk is not applicable because mechlorethamine is a small-molecule drug.
• Any generic launch before patent expiration would likely require a Paragraph IV strategy, a settlement, a license, or a formulation that avoids the listed claims.

FAQs About U.S. Patent 9,382,191

Is U.S. Patent 9,382,191 a compound patent for mechlorethamine?

No. The claims provided are topical composition claims. They do not broadly claim mechlorethamine as a chemical compound.

Does the patent require the commercial Valchlor concentration of 0.016%?

No. The claims require at least about 0.001% by weight. They do not limit the formulation to 0.016%.

Can a generic avoid the patent by changing only the mechlorethamine salt?

Possibly, but not automatically. Claim 1 covers mechlorethamine and pharmaceutically acceptable salts, while claim 18 specifically requires the HCl salt. The complete formulation must be analyzed against each claim.

Does adding water automatically avoid infringement?

No. The effect depends on whether the resulting product remains a “non-aqueous vehicle or carrier” under the claim construction and whether all other limitations are met.

Does the patent block an over-the-counter mechlorethamine product?

The patent does not depend on prescription status. A product would face the same composition-claim analysis regardless of whether it is marketed by prescription or under another regulatory category.

References

1. U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

2. U.S. Food and Drug Administration. (n.d.-b). Valchlor (mechlorethamine hydrochloride) gel prescribing information. https://www.accessdata.fda.gov/drugsatfda/

3. U.S. Patent and Trademark Office. (2016). U.S. Patent No. 9,382,191, topical compositions. https://patents.google.com/patent/US9382191B2

4. U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-adjustment

5. Hatch-Waxman Amendments, 21 U.S.C. § 355.

Drugs Protected by US Patent 9,382,191

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Helsinn	VALCHLOR	mechlorethamine hydrochloride	GEL;TOPICAL	202317-001	Aug 23, 2013		RX	Yes	Yes	9,382,191		Y

International Family Members for US Patent 9,382,191

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1858864		PA2017026	Lithuania
European Patent Office	1858864		CR 2017 00033	Denmark
European Patent Office	1858864		300888	Netherlands