Details for Patent: 6,340,695

Summary for Patent: 6,340,695

Title:	Rapid onset formulation
Abstract:	Provided herein is a novel enterically-coated pyridoxine HCl and doxylamine succinate rapid onset formulation comprising a disintegrating agent such that the following dissolution profiles are satisfied when measured in 1000 ml phosphate buffer at pH 6.8 and 37° C. in a type 2 dissolution apparatus at 100 rpm:(a) at least about 40% of the total pyridoxine HCl and doxylamine succinate is dissolved after 30 minutes of measurement;(b) at least about 70% of the total pyridoxine HCl and doxylamine succinate is dissolved after 60 minutes of measurement;(c) at least about 80% of the total pyridoxine HCl and doxylamine succinate is dissolved after 90 minutes of measurement;(d) at about 90% of the total pyridoxine HCl and doxylamine succinate is dissolved after 120 minutes of measurement.Preferably the formulation will contain a core coated with at least one enteric coating, the core comprising pyridoxine HCl, doxylamine succinate and the following non-active excipients: a filler or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent.
Inventor(s):	Eric Gervais
Assignee:	Duchesnay Inc
Application Number:	US09/885,051
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,340,695
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device;

United States Patent 6,340,695: Claim Scope, Expiration, Litigation Risk, and Patent Landscape

U.S. Patent No. 6,340,695 covers an enterically coated, rapid-onset oral formulation containing pyridoxine hydrochloride and doxylamine succinate. Its core limitation is not merely the active-ingredient combination. The claims require specified dissolution performance in pH 6.8 phosphate buffer, together with defined tablet-core excipients and coating architecture in narrower claims.

The patent was associated with the delayed-release doxylamine/pyridoxine product Diclegis. Based on the listed patent term, U.S. Patent 6,340,695 expired in September 2020 and is no longer an enforceable barrier to current U.S. generic entry. It remains relevant as prior art, as a technical benchmark, and in analyzing historical Paragraph IV litigation and later patent filings.

What does U.S. Patent 6,340,695 protect?

The patent protects a pharmaceutical dosage form that combines:

• Pyridoxine hydrochloride, or vitamin B6
• Doxylamine succinate
• An enteric coating
• A disintegrating agent
• A rapid dissolution profile measured under a specified laboratory protocol

The broadest formulation claims are claims 1 and 2. They are performance-defined claims. A competing product must satisfy the specified dissolution thresholds to fall within the literal scope of either claim, assuming the other limitations are also met.

Independent claim structure

Claim	Subject matter	Principal limitations
1	Formulation	Enteric-coated pyridoxine HCl and doxylamine succinate; disintegrating agent; dissolution thresholds at 30, 60, 90 and 120 minutes
2	Formulation	Claim 1 formulation with additional thresholds at 15, 45 and 75 minutes
25	Treatment method	Administering claim 1 formulation to treat nausea and vomiting
26	Treatment method	Administering claim 2 formulation to treat nausea and vomiting
27	Pregnancy treatment	Administering claim 1 formulation for nausea and vomiting during pregnancy
28	Pregnancy treatment	Administering claim 2 formulation for nausea and vomiting during pregnancy
29	Medicament	Medicament consisting essentially of the claim 5 formulation
30	Medicament	Medicament consisting essentially of the claim 6 formulation

Claims 3 and 4 add a particularly demanding five-minute dissolution requirement. Claims 5 through 24 define the tablet core, excipient identities, percentage ranges and aqueous coating structure.

How do the dissolution limitations define infringement?

The principal technical boundary is the dissolution method. The claims require testing:

• In 1,000 mL of phosphate buffer
• At pH 6.8
• At 37°C
• In a Type 2 dissolution apparatus
• At 100 rpm

The formulation must release at least the stated percentage of each active ingredient. The requirement applies separately to pyridoxine HCl and doxylamine succinate. A product that releases sufficient pyridoxine but insufficient doxylamine, or the reverse, would not satisfy the limitation as written.

Claim 1 dissolution profile

Measurement time	Minimum dissolution of each active
30 minutes	About 40%
60 minutes	About 70%
90 minutes	About 80%
120 minutes	About 90%

Claim 2 additional dissolution profile

Measurement time	Minimum dissolution of each active
15 minutes	About 20%
45 minutes	About 60%
75 minutes	About 80%

Claim 2 incorporates claim 1 and therefore requires both the claim 1 profile and the additional intermediate time-point requirements. Claims 3 and 4 require at least about 40% dissolution within five minutes, making them narrower than claims 1 and 2.

The dissolution limitations create a product-testing issue. In a patent dispute, the parties would likely contest:

1. The precise identity and qualification of the test product.
2. Whether “about” permits a measurable tolerance.
3. Whether dissolution is calculated against labeled amount, assay amount or another total amount.
4. Sampling, filtration and analytical methodology.
5. Whether both active ingredients must meet every threshold in every tested unit.
6. The significance of batch-to-batch variability.

What formulations are protected by claims 5 through 24?

Claims 5 through 24 protect a specific tablet-core and coating configuration. The core must contain both active ingredients and the following excipient categories:

• A filler or binder
• A disintegrating agent
• A lubricant
• A silica flow conditioner
• A stabilizing agent

The dependent claims narrow those categories to particular materials.

Function	Claimed material
Filler or binder	Microcrystalline cellulose
Disintegrant	Sodium croscarmellose
Lubricant	Magnesium stearate
Flow conditioner	Silicon dioxide
Stabilizer	Magnesium trisilicate

Claims 17 and 18 define broad percentage ranges:

Core component	Claimed range
Pyridoxine HCl	About 4% to 10%
Doxylamine succinate	About 4% to 10%
Microcrystalline cellulose	About 40% to 80%
Magnesium trisilicate	About 10% to 30%
Silicon dioxide	About 0.5% to 5%
Sodium croscarmellose	About 0.5% to 5%
Magnesium stearate	About 0.5% to 5%

Claims 19 and 20 recite a narrower nominal composition:

• 7% pyridoxine HCl
• 7% doxylamine succinate
• 62% microcrystalline cellulose
• 18% magnesium trisilicate
• 1% silicon dioxide
• 3% sodium croscarmellose
• 3% magnesium stearate

The stated percentages total 101%, which may reflect rounding. That issue would be relevant to claim construction and written-description analysis, but it does not by itself invalidate the claim. Courts generally assess the claim in light of the specification and the meaning a skilled person would assign to rounded formulation percentages.

Claims 21 through 24 require an aqueous-based coating. Claims 23 and 24 further require a three-layer structure:

1. Seal coat applied to the core
2. Enteric coating applied over the seal coat
3. Aesthetic top coat applied over the enteric layer

A product using a nonaqueous coating system could avoid these narrower claims, but it could still implicate claims 1 and 2 if it satisfies the broader enteric-coating and dissolution limitations.

How strong is the patent estate for the claimed formulation?

The patent’s historical strength was mixed.

Claims 1 and 2 were technically broad because they did not require the specific excipients or precise percentage composition found in claims 17 through 20. They did, however, require a particular combination of:

• Enteric protection
• Doxylamine succinate and pyridoxine HCl
• A disintegrating agent
• Rapid release after the dosage form reaches pH 6.8 medium

The narrower claims provide more specific fallback positions but are easier to design around. A competitor could potentially avoid them by changing:

• The filler or binder
• The disintegrant
• The stabilizer
• The coating system
• The excipient proportions
• The tablet architecture
• The release profile

The main vulnerability of claims 1 and 2 is that dissolution performance may be difficult to distinguish from an inherent result of a known enteric-coated immediate-release core. If prior art disclosed the same active ingredients, enteric coating and rapidly disintegrating excipients, an accused infringer could challenge novelty or obviousness based on the claimed performance profile.

The main strength is the cumulative nature of the requirements. A challenger would need to establish that the prior art disclosed or rendered obvious the specific formulation and the claimed dissolution behavior under the stated test conditions.

When did U.S. Patent 6,340,695 expire?

U.S. Patent 6,340,695 expired in September 2020 based on the patent’s applicable term and listed Orange Book term information. It therefore does not presently block manufacture, approval or marketing of a U.S. generic formulation on patent grounds.

Event	Date or status
U.S. patent issuance	January 22, 2002
Associated product	Diclegis delayed-release tablets
FDA approval of Diclegis NDA 021876	April 8, 2013
Listed patent term	September 2020
Current enforceability	Expired
Current practical role	Prior art and historical patent-landscape reference

The patent’s expiration does not eliminate regulatory requirements. A generic applicant still must demonstrate pharmaceutical equivalence, bioequivalence or applicable product-specific equivalence, manufacturing quality and compliance with FDA labeling requirements.

What was the Orange Book status of U.S. Patent 6,340,695?

Patent 6,340,695 was listed in the FDA Orange Book for Diclegis, a delayed-release tablet containing doxylamine succinate and pyridoxine hydrochloride. Orange Book listing made the patent relevant to abbreviated new drug applications and Hatch-Waxman certifications.

For a generic applicant filing before expiration, the principal certification options would have included:

• Paragraph I: no patent information listed
• Paragraph II: patent expired
• Paragraph III: applicant will wait for expiration
• Paragraph IV: patent is invalid, unenforceable or will not be infringed

After expiration, the relevant certification would ordinarily be Paragraph II, assuming no later unexpired listed patent applies to the proposed product.

The Orange Book listing itself did not establish patent validity. It triggered statutory notice and, if followed by timely litigation, could generate a 30-month stay of approval under the Hatch-Waxman Act. The stay mechanism is statutory and does not extend the underlying patent term. [FDA, 2024; 21 U.S.C. § 355(j)]

Which companies challenged or could have challenged the patent?

The patent was exposed to generic competition because it covered a small-molecule oral product. Potential challengers included manufacturers developing doxylamine/pyridoxine delayed-release tablets under an ANDA.

A complete company-by-company Paragraph IV history cannot be established from the claim text alone. Patent litigation records must be matched to:

• The specific ANDA number
• The notice-letter date
• The asserted claims
• The district court action
• Any Federal Circuit appeal
• The settlement terms
• The product’s final approval date

The major strategic point is that any Paragraph IV dispute concerning patent 6,340,695 became commercially obsolete when the patent expired, unless the dispute involved damages for pre-expiration activity or a separate patent estate.

What patent litigation affected Diclegis and the formulation?

The principal litigation risk would have involved a generic product with the same active ingredients and delayed-release design. The likely infringement theories would have focused on:

• Literal satisfaction of the dissolution thresholds
• Inherent or intentional inclusion of a disintegrant
• Enteric-coated tablet construction
• Equivalence of excipients
• Method-of-use claims directed to pregnancy-related nausea and vomiting

The formulation claims would be stronger against a product that copied the listed core composition. Claims 17 through 20 create a direct comparison point for reverse-engineering evidence. Claims 25 through 28 could present method-of-use issues, but method claims are harder to enforce against a generic applicant where the proposed labeling omits or narrows the patented indication.

The statutory safe-harbor provision for activities reasonably related to submission of an ANDA can protect pre-approval development and testing. Commercial manufacture and sale after patent expiration are different questions. [35 U.S.C. § 271(e)(1)]

Are there later patents covering Diclegis or similar products?

Patent 6,340,695 should not be treated as the entire Diclegis estate. Drug-product patent landscapes often contain later patents directed to:

• Specific delayed-release formulations
• Dosing regimens
• Tablet strength combinations
• Pharmacokinetic performance
• Use in pregnancy
• Manufacturing processes
• Coating materials
• Stability or packaging

Later patents can create a separate Orange Book or litigation analysis even after the 6,340,695 patent expires. The commercial freedom-to-operate question therefore depends on the complete FDA listing and the relevant patent family, not on patent 6,340,695 alone.

The distinction is important:

Patent category	Relevance to 6,340,695
Core formulation patent	Directly analyzed here
Later formulation patent	May create separate post-2020 risk
Method-of-use patent	May affect labeling and inducement risk
Manufacturing patent	May affect process-based infringement
Packaging or stability patent	Usually narrower commercial exposure
Regulatory exclusivity	Separate from patent term

Does biosimilar risk apply to this product?

No. Diclegis and equivalent doxylamine/pyridoxine products are chemically synthesized small-molecule drugs, not biologics. The relevant competitive pathway is an ANDA under section 505(j), not a biosimilar application under section 351(k).

The competitive risks are therefore:

• Generic delayed-release tablets
• Authorized generic supply
• Reformulated branded products
• Alternative doxylamine/pyridoxine dosage forms
• Competing antiemetic products used during pregnancy

What generic launch scenarios existed after patent expiration?

Once the patent expired, three commercial launch scenarios became available.

Direct equivalent launch

A manufacturer could pursue an equivalent delayed-release tablet containing the same active ingredients and a comparable release profile. This is the most direct competitive route but may require product-specific bioequivalence and manufacturing controls.

Design-around launch

A manufacturer could alter the excipient system, coating process or dissolution behavior. This could reduce exposure to narrower formulation claims and later patents, although a design-around might complicate regulatory comparability.

Authorized or licensed generic launch

The brand owner or its commercial partner could supply an authorized generic. This strategy can preserve manufacturing utilization and control channel pricing while limiting independent generic share.

Because patent 6,340,695 expired in 2020, it no longer supports a forward-looking patent-based launch delay. Any present launch risk must be assessed against later unexpired patents, FDA exclusivity, product-specific requirements and commercial contracting.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove technical barriers. A competitive manufacturer must still control:

• Uniform distribution of low-dose active ingredients
• Tablet mechanical strength
• Enteric-coating integrity
• Moisture protection
• Stability of pyridoxine HCl
• Compatibility of magnesium trisilicate with the active ingredients
• Rapid core disintegration after enteric-coat dissolution
• Reproducible dissolution at all claimed time points
• Scale-up from laboratory compression to commercial production

The claimed excipient combination is not, by itself, a manufacturing monopoly after patent expiration. Trade secrets, process know-how, supplier qualification and product-specific FDA requirements may remain commercially relevant.

How does U.S. Patent 6,340,695 compare with competing patent strategies?

Strategy	Protection focus	Design-around difficulty	Post-expiration value
6,340,695 core formulation	Dissolution profile and enteric-coated tablet	Moderate	Prior-art and technical benchmark
Narrow excipient claims	Specific core composition	Low to moderate	Limited
Method-of-use claims	Treatment of nausea and vomiting, including pregnancy	Moderate	Limited after expiration
Later formulation patents	New release, strength or stability attributes	Depends on claim	Potentially material
Manufacturing patents	Process steps and coating/compression controls	Variable	Can remain material if unexpired

The most commercially important claims in 6,340,695 were claims 1 and 2 because they captured formulation performance without requiring every named excipient. Claims 17 through 20 were useful fallback claims but had a narrower enforcement perimeter.

Key Takeaways

• U.S. Patent 6,340,695 covers enterically coated pyridoxine HCl/doxylamine succinate formulations with defined rapid dissolution profiles.
• Claims 1 and 2 are the principal broad formulation claims.
• Claims 3 and 4 add five-minute dissolution requirements.
• Claims 5 through 24 narrow the invention through excipient identity, concentration ranges and aqueous three-layer coating structure.
• Claims 25 through 28 cover treatment of nausea and vomiting, including pregnancy-related nausea and vomiting.
• Claims 29 and 30 cover medicaments based on the specified core formulation.
• The patent expired in September 2020 and is no longer a current U.S. patent barrier.
• The product is a small molecule, so biosimilar law does not apply.
• Current market-entry analysis must focus on later patents, Orange Book listings, FDA product-specific requirements and commercial barriers.
• The principal technical risk in copying the formulation is reproducibly meeting both active-ingredient dissolution profiles under the specified test method.

FAQs

Was U.S. Patent 6,340,695 a patent on Diclegis itself?

It was a formulation patent associated with Diclegis, not a generic monopoly over every use of doxylamine and pyridoxine. Its claims required the particular enteric-coated formulation and dissolution characteristics recited in the patent.

Could a generic avoid the patent by using different excipients?

Before expiration, a generic could potentially avoid narrower claims by changing the excipient system. Avoiding claims 1 and 2 would also require avoiding the claimed enteric-coated formulation and dissolution limitations, not merely changing one excipient.

Did the patent cover immediate-release doxylamine and pyridoxine tablets?

The claims are directed to an enterically coated rapid-onset formulation. A conventional immediate-release product without the claimed enteric coating would not literally satisfy the formulation claims.

Does patent expiration permit use of the exact claimed formulation?

Patent expiration removes the patent-based restriction under 6,340,695. It does not remove FDA approval, manufacturing, labeling, quality or intellectual-property obligations arising from other unexpired patents or agreements.

Why are the dissolution conditions important in a patent dispute?

They provide an objective test for a key claim limitation. The accused product’s release of each active ingredient must be evaluated under the specified buffer, temperature, apparatus, agitation speed and time points.

References

1. U.S. Patent No. 6,340,695. (2002). Rapid onset formulation comprising pyridoxine hydrochloride and doxylamine succinate. U.S. Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2013). Diclegis prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

4. Hatch-Waxman Amendments, 21 U.S.C. § 355(j).

5. Patent Act, 35 U.S.C. § 271(e)(1).

6. Patent Term, 35 U.S.C. § 154.

Drugs Protected by US Patent 6,340,695

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,340,695

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	034380
Austria	307582
Australia	2001272243
Belgium	1014929
Brazil	0107371
Canada	2350195