United States Patent 8,618,164: Claim Scope, Validity Risks, Orange Book Position, and Generic Entry Analysis

U.S. Patent No. 8,618,164 protects a treatment sequence for knee osteoarthritis: apply topical diclofenac containing 40% to 50% dimethyl sulfoxide, allow the treated area to dry, and then apply a different prescription topical medication to the same area during the diclofenac treatment course. The patent is directed primarily to co-administration technique, not to diclofenac as a molecule.

The narrowest commercial read-through is a Pennsaid-type topical diclofenac sodium solution containing approximately 1.5% diclofenac sodium and 45.5% dimethyl sulfoxide, followed by another prescription topical drug. The claims do not cover every use of topical diclofenac, every use of Pennsaid, or every combination of topical products.

What does U.S. Patent 8,618,164 protect?

The independent claims protect a sequence of patient-treatment steps:

Apply topical diclofenac to a painful knee to treat knee osteoarthritis.
Use a diclofenac preparation containing 40% to 50% w/w dimethyl sulfoxide.
Wait until the treated area is dry.
Apply a different prescription topical medication to the same treated area.
Perform the second application during the course of treatment with the diclofenac preparation.

Claim 8 adds a further limitation: the initial diclofenac application must not enhance systemic absorption of the subsequently applied prescription topical medication.

The patent therefore covers a method of using a formulation, rather than merely the formulation itself. A product manufacturer or healthcare provider would face an infringement issue only if the accused conduct satisfies the required formulation, disease, body site, sequence, drying, and second-medication limitations.

Patent identification

Item	Description
Patent	U.S. Patent No. 8,618,164
Title	Methods of applying topical agents
Issue date	December 31, 2013
Technology	Sequential application of topical diclofenac and another prescription topical medication
Principal formulation limitation	40% to 50% w/w dimethyl sulfoxide
Key commercial formulation	Approximately 1.5% w/w diclofenac sodium and 45.5% w/w dimethyl sulfoxide
Claim type	Method of treatment and administration
Likely product association	Pennsaid-type topical diclofenac solution
Statutory term baseline	Twenty years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and maintenance-fee status [1]

The patent front page and USPTO Patent Center control the official priority, assignment, maintenance-fee, and term data [1, 2].

How broad are the independent claims?

Claim 1 is broader than the dependent claims because it does not require the 1.5% diclofenac sodium concentration, the 45.5% dimethyl sulfoxide concentration, or the specific excipient combination.

Claim 1 scope

Claim 1 requires:

a patient with knee pain;
treatment of osteoarthritis of the knee;
application to an area of the knee;
a topical diclofenac preparation;
a therapeutically effective amount of diclofenac or an acceptable salt;
40% to 50% w/w dimethyl sulfoxide;
drying before the second product is applied;
a second prescription topical medication;
a second medication different from the diclofenac product;
application to the same treated area;
application during the diclofenac treatment course.

The use of “comprising” in the formulation language generally permits additional ingredients beyond those expressly listed. Thus, claim 1 is not limited to a formulation containing only diclofenac and dimethyl sulfoxide.

The formulation range is important. A product containing 45.5% dimethyl sulfoxide falls within the literal range. A formulation containing 39.9% or 50.1% may avoid literal infringement of the range, although the doctrine of equivalents could remain relevant depending on prosecution history and the technical differences.

Claim 8 scope

Claim 8 resembles claim 1 but expressly requires that the initial diclofenac application does not enhance systemic absorption of the second prescription topical medication.

That limitation creates an additional technical and evidentiary issue. An accused party could contest whether the “does not enhance” requirement is satisfied based on pharmacokinetic studies, comparative permeation testing, formulation data, or the meaning assigned to “enhance” during claim construction.

Claim 8 is not necessarily narrower in every respect than claim 1 as a practical matter. It uses “therapeutically effective amount of diclofenac” without expressly requiring “or a pharmaceutically acceptable salt thereof” in the same language, although the dependent claims and specification may inform interpretation. The central additional restriction is the systemic-absorption limitation.

What do the dependent claims add?

Claim	Added limitation	Commercial significance
2	About 45.5% w/w dimethyl sulfoxide	Closely tracks a Pennsaid-type formulation
3	1.5% w/w diclofenac sodium	Narrows the claim to the principal diclofenac sodium strength
4	Ethanol, propylene glycol, glycerine, and water	Captures a defined excipient system
5	Sodium, potassium, diethylamine, or epolamine diclofenac salt	Broadens salt coverage while limiting the salt list
6	Diclofenac sodium	Commercially relevant salt-specific claim
7	Initial application does not enhance systemic absorption of the second medication	Adds a pharmacokinetic limitation to claim 1

Claims 2, 3, and 4 are the most relevant to a branded or generic 1.5% diclofenac sodium solution containing approximately 45.5% dimethyl sulfoxide. Claims 5 and 6 are more useful against alternative diclofenac salt products.

What formulations are protected by U.S. Patent 8,618,164?

The patent is strongest against formulations and uses with the following profile:

diclofenac sodium at approximately 1.5% w/w;
dimethyl sulfoxide at approximately 45.5% w/w;
ethanol;
propylene glycol;
glycerine;
water;
topical application to the knee;
treatment of knee osteoarthritis;
a subsequent prescription topical product applied after drying.

The claims do not expressly require the commercial product name Pennsaid. A generic product could fall within the claims if it has the claimed composition and is used in the claimed sequence.

The patent does not appear, from the supplied claims, to cover:

oral diclofenac;
injectable diclofenac;
diclofenac gel lacking the claimed dimethyl sulfoxide range;
topical diclofenac applied to the hand, shoulder, ankle, or another body site;
diclofenac used for a condition other than knee osteoarthritis;
use without a second prescription topical medication;
simultaneous application without the required drying interval;
a second product applied to a different body area;
a second nonprescription topical product, if “prescription medication” is construed as requiring prescription status.

When does Patent 8,618,164 lose exclusivity?

The statutory expiration date depends on the earliest effective nonprovisional filing date, patent-term adjustment, and maintenance-fee payment history. A patent generally expires 20 years after the earliest effective nonprovisional filing date under 35 U.S.C. §154, subject to adjustment or extension [3].

The issue date, December 31, 2013, does not determine the expiration date. Patent-term analysis should use:

the priority and filing data on the patent;
any patent-term adjustment shown by the USPTO;
any terminal disclaimer;
payment of the 3.5-, 7.5-, and 11.5-year maintenance fees;
any patent-term extension under 35 U.S.C. §156.

A patent can remain within its nominal term but become unenforceable after an unpaid maintenance fee. Conversely, a late payment or accepted petition may restore enforceability. The USPTO Patent Center record is controlling for current status [2].

Patent term versus regulatory exclusivity

Patent expiration and FDA exclusivity are separate rights. FDA approval of a generic topical diclofenac product can be delayed by listed patents, regulatory exclusivity, or both. A method-of-use patent does not automatically block every abbreviated new drug application for the underlying diclofenac formulation.

What is the Orange Book status of Patent 8,618,164?

The Orange Book lists patents submitted by NDA sponsors for approved drug products and identifies the approved use or product to which a patent relates [4]. A method-of-use patent may be listed if it claims an approved use of the drug and satisfies FDA listing requirements.

For a Pennsaid-related product, the relevant question is whether 8,618,164 appears in the current or historical Orange Book entry for the applicable NDA, together with:

the patent number;
the expiration date recorded by FDA;
the use code;
the NDA or product strength;
any delisting, correction, or dispute history.

The claims supplied are method-of-use claims directed to sequential topical therapy for knee osteoarthritis. If listed, the patent would be more relevant to a generic seeking labeling that permits or describes the claimed combination-use regimen than to an ANDA limited to a non-infringing use.

FDA’s Orange Book does not decide infringement or validity. It records sponsor-submitted patent information and regulatory effects. Patent listing disputes and Paragraph IV consequences are governed by the Hatch-Waxman framework and FDA regulations [4, 5].

What Paragraph IV challenges could target this patent?

An ANDA applicant could address the patent through one or more certifications:

Paragraph I, if no patent information is listed;
Paragraph II, if the patent has expired;
Paragraph III, if approval is deferred until patent expiration;
Paragraph IV, if the patent is invalid, unenforceable, or not infringed;
a section viii statement, if the applicant omits the patented method from labeling.

For this patent, a Paragraph IV non-infringement theory could focus on:

no intent to apply a second prescription topical medication;
no treatment of knee osteoarthritis;
use on a body site other than the knee;
a dimethyl sulfoxide concentration outside 40% to 50%;
no waiting period until the first area is dry;
application of the second product to a different area;
a second product that is not a prescription medication;
labeling that excludes the patented sequential use.

A validity challenge could address written description, enablement, indefiniteness, anticipation, obviousness, and claim construction. The most litigation-sensitive terms are likely “after said treated area is dry,” “during a course of treatment,” “prescription medication,” and “does not enhance the systemic absorption.”

How strong is the patent estate for topical diclofenac?

Patent 8,618,164 appears to be a secondary-use patent layered over the underlying topical diclofenac product. Its commercial strength depends less on ownership of the diclofenac formulation and more on whether the sponsor can prove that the approved product’s labeling, physician instructions, or routine clinical use causes the claimed sequence.

Strengths

The 40% to 50% dimethyl sulfoxide range maps onto a specific commercial formulation.
The 45.5% dependent claim provides a narrow formulation anchor.
The 1.5% diclofenac sodium claim targets a commercially important strength.
The claim requires a particular sequence that may be included in prescribing or administration instructions.
The same-area and drying requirements create a concrete infringement framework.

Weaknesses

The claims require a second prescription topical product, which may not be part of the approved label.
Method-of-treatment enforcement can be difficult where the manufacturer sells only the first product.
“Dry” may create claim-construction and proof disputes.
The underlying concept of applying separate topical agents sequentially may face obviousness arguments based on topical treatment practice.
A generic can potentially use a section viii carve-out or restrictive labeling if the FDA-approved indication permits it.
The patent does not control formulations outside the claimed dimethyl sulfoxide range unless equivalents apply.

What patent litigation affects U.S. Patent 8,618,164?

The supplied claims do not identify a litigation case, settlement agreement, consent judgment, or Paragraph IV notice. A reliable litigation assessment requires checking PACER, the USPTO Patent Center file, FDA Orange Book records, and relevant Federal Circuit or district court opinions.

The principal litigation questions would be:

whether the patent was listed against the relevant NDA;
whether an ANDA applicant served a Paragraph IV notice;
whether the NDA holder filed a Hatch-Waxman action within 45 days;
whether a 30-month stay arose;
whether the case settled;
whether the settlement included a license, launch date, or labeling restriction;
whether the patent was challenged at the Patent Trial and Appeal Board.

Without a confirmed case record, no litigation outcome or settlement date should be attributed to this patent.

How does Patent 8,618,164 compare with formulation and method-of-use patents?

Patent category	Typical protected subject matter	Relevance of 8,618,164
Drug-substance patent	Diclofenac molecule or salt	Not the principal subject of the supplied claims
Formulation patent	Concentrations, solvents, excipients, delivery system	Partially relevant through the claimed formulation limitations
Method-of-use patent	Treating a disease with a drug	Directly relevant
Administration-sequence patent	Timing or order of applying products	Core subject of 8,618,164
Manufacturing patent	Preparation, mixing, filling, or process controls	Not covered by the supplied claims
Device or delivery patent	Applicator, metered dose, or delivery system	Not covered by the supplied claims

The patent is therefore most exposed to a design-around that changes the formulation, indication, body site, sequence, or labeling. It is less useful as a barrier against a generic that makes the diclofenac solution but does not promote or direct the patented co-application method.

What generic entry risks exist for a Pennsaid-type product?

Generic entry risk has two separate components:

formulation and product approval risk; and
method-of-use patent risk.

A generic applicant could obtain approval for a topical diclofenac solution while attempting to avoid the patent through a carved-out label. The practical risk increases if the reference product’s labeling expressly instructs users to apply another prescription topical medication after drying.

The risk is lower where:

the generic formulation contains a different dimethyl sulfoxide concentration;
the label omits sequential combination use;
the product is approved for a different indication;
the applicant can demonstrate that its label does not induce the patented method;
the patent is not listed or has expired;
the relevant claims are invalidated or held unenforceable.

The risk is higher where a generic matches the 1.5% diclofenac sodium and approximately 45.5% dimethyl sulfoxide formulation and the sponsor alleges that the product is intended for the same knee osteoarthritis regimen.

What are the licensing and geographic rights?

A U.S. patent creates rights only in the United States. It does not block manufacture, sale, or use in Canada, Europe, Japan, or other jurisdictions unless corresponding national patents exist.

Licensing analysis should distinguish:

assignment of the patent;
exclusive U.S. license;
nonexclusive formulation license;
NDA commercialization rights;
settlement-based launch license;
supply or distribution arrangements.

The patent record can identify assignments and recorded interests, but a recorded assignment does not disclose every private license or royalty arrangement. No licensing deal should be inferred solely from the patent’s assignee or commercial association with a diclofenac product.

Key Takeaways

U.S. Patent 8,618,164 is primarily a method-of-treatment and sequential-application patent.
Its core requirement is topical diclofenac containing 40% to 50% w/w dimethyl sulfoxide, followed after drying by a different prescription topical medication applied to the same knee area.
Claims 2, 3, and 4 closely target a 1.5% diclofenac sodium, approximately 45.5% dimethyl sulfoxide formulation with specified excipients.
The patent does not cover all topical diclofenac products or all uses of Pennsaid.
Generic risk depends heavily on labeling, physician instructions, and whether the second topical medication is promoted as part of the treatment regimen.
A section viii carve-out or formulation design-around may reduce infringement exposure.
Expiration must be confirmed from the USPTO term and maintenance-fee records, while Orange Book status must be confirmed from the applicable NDA listing.
The supplied information does not establish a particular Paragraph IV case, settlement, license, or final validity ruling.

FAQs

Can a topical diclofenac gel infringe Patent 8,618,164?

Not necessarily. The accused product must satisfy the claimed dimethyl sulfoxide range and the claimed sequential application method. A conventional diclofenac gel without 40% to 50% dimethyl sulfoxide would generally fall outside the literal formulation language.

Does applying a steroid cream after diclofenac create infringement risk?

It can, if the steroid is a prescription topical medication, is applied to the same knee area after the diclofenac-treated area dries, and the diclofenac treatment satisfies the remaining claim limitations.

Can a generic avoid the patent by changing the diclofenac salt?

Potentially. Claims 1 and 8 broadly refer to diclofenac or, depending on claim construction, its therapeutically effective form, while claims 5 and 6 expressly address specified salts and diclofenac sodium. A salt change does not automatically avoid every claim.

Does the patent cover simultaneous application of two topical medications?

The claims require the second medication to be applied subsequently and after the treated area is dry. Simultaneous application would not satisfy those express limitations.

Is a patent listing proof that the patent is valid and enforceable?

No. An Orange Book listing is a regulatory record of patent information submitted for an approved drug. It does not adjudicate validity, enforceability, infringement, or the proper construction of the claims.

References

U.S. Patent No. 8,618,164, Methods of applying topical agents (issued Dec. 31, 2013), United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/
35 U.S.C. § 154. Patent term.
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/
21 C.F.R. §§ 314.50, 314.94, 314.107. Abbreviated new drug applications and patent certifications.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Horizon	PENNSAID	diclofenac sodium	SOLUTION;TOPICAL	204623-001	Jan 16, 2014		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial				USE OF TOPICAL DICLOFENAC ON THE KNEE AND A SECOND TOPICAL PRESCRIPTION MEDICATION ON THE SAME KNEE	⤷ Start Trial
Nuvo Pharms Inc	PENNSAID	diclofenac sodium	SOLUTION;TOPICAL	020947-001	Nov 4, 2009		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial				USE OF TOPICAL DICLOFENAC ON THE KNEE AND A SECOND TOPICAL PRESCRIPTION MEDICATION ON THE SAME KNEE	⤷ 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: 8,618,164

Which drugs does patent 8,618,164 protect, and when does it expire?

Summary for Patent: 8,618,164