Details for Patent: 6,730,679

Summary for Patent: 6,730,679

Title:	Pharmaceutical formulations
Abstract:	Pharmaceutical formulations containing HIV protease inhibitors, specifically including 3S-[3R*(1R*,2S*)]-[3-[[(4-aminophenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]carbamic acid, tetrahydro-3-furanyl ester (alternatively known as VX 478 or 141W94), and a tocopherol, and their use in medical therapy are described.
Inventor(s):	Arup K. Roy, Lloyd Gary Tillman
Assignee:	Glaxo Group Ltd , SmithKline Beecham Corp
Application Number:	US08/820,848
Patent Claim Types: see list of patent claims	Formulation; Compound; Dosage form;

United States Patent 6,730,679 (US 6,730,679): Scope, Claims Construction, and Patent Landscape

US 6,730,679 is a US formulation patent with a narrow core claim to a specific active stereoisomer, paired with a specific “water soluble tocopherol” excipient (typically Vitamin E-TPGS) and a defined hydrophilic non-aqueous solvent system (often PEG + propylene glycol) to achieve “unexpectedly enhanced bioavailability.” The patent’s enforceable scope centers on (i) the exact API identity (3S-[3R(1R,2S*)]-…-tetrahydro-3-furanyl ester), (ii) the tocopherol derivative being water soluble (especially Vitamin E-TPGS), and (iii) the solvent system being miscible/hydrophilic and present within disclosed weight ranges and dosage forms (solution, capsule, soft gelatin capsule).

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What does US 6,730,679 claim to protect: formulation scope and enforceable elements?

Short answer: US 6,730,679 protects oral pharmaceutical formulations combining the specified carbamic acid tetrahydro-3-furanyl ester active with a water soluble tocopherol derivative (Vitamin E-TPGS) and a miscible hydrophilic non-aqueous solvent system, in specified ratios and forms, when the formulation shows unexpectedly enhanced bioavailability.

Core claim architecture (how claim 1 builds a composition)

Claim 1 (independent) recites a three-part composition:

1. Active ingredient (strict identity)

   • 3S-[3R(1R,2S*)]-[3-[4-aminophenyl)sulphonyl-amino]-2-hydroxy-1-phenylmethyl)propyl]carbamic acid, tetrahydro-3-furanyl ester
     This level of stereochemical specificity is typically a strong limitation for infringement and design-around.

2. Absorption/permeation excipient

   • A water soluble tocopherol derivative
   • Dependent claims identify the specific embodiment: Vitamin E-TPGS.

3. Solvent system

   • A hydrophilic non-aqueous solvent miscible with the water soluble tocopherol derivative
     Dependent claims define a frequent embodiment: mixture of polyethylene glycol and propylene glycol (claim 7) and broader alternatives including PEG, propylene glycol, polyvinyl pyrrolidone.

4. Performance attribute

   • “Possessing unexpectedly enhanced bio-availability” This is a functional/empirical requirement. In enforcement, it can become central to claim construction and validity challenges tied to unpredictability and comparative data.

What the dependent claims add (scope expansion vs limitation)

Dependent claims tighten or specify:

• Amount and ratio limits

  • Vitamin E-TPGS at least 20% (claim 2)
  • Active:tocopherol ratio ~ 1:0.5 to 1:3 w/w (claim 3)
  • Active amount ~10 to 1500 mg (claims 6 and 9)
  • Alternative broad blend ratio ranges (claim 11, claim 18)

• Specific excipients

  • Vitamin E-TPGS explicitly (claims 4, 10, 19; also claim 13/15)
  • Solvent specifics: PEG + propylene glycol (claim 7), or PEG/propylene glycol/PVP combos (claim 18)

• Dosage form / presentation

  • Capsule (claim 5), solution (claim 8), soft gelatin capsule (claims 12, 14, 20, 21)

Independent claim set (composition breadth map)

From the text provided, there are at least three independent-like groupings:

• Claim 1: composition with (API + water soluble tocopherol derivative + hydrophilic non-aqueous solvent miscible with it) plus unexpected bioavailability.
• Claim 11: explicit ranges for (API + 10–60% tocopherol derivative + defined solvent miscible with tocopherol), with ratio 1:0.5 to 1:10 w/w and the unexpected bioavailability requirement.
• Claim 18: defines solvent selection set (PEG, propylene glycol, PVP, or combination) plus quantitative ranges (API 1–50%, tocopherol 10–60%, solvent 15–95%) and again “unexpectedly enhanced bioavailability.”
• Claim 21: concrete formulation percentages (19% API, 51% Vitamin E-TPGS, 25% PEG, 5% propylene glycol) in an oral administration context.

Practical read: The claim scope is not “any formulation” of the API; it is “a formulation with this API stereochemical species plus this class of solubilizer system (water soluble tocopherol derivative + hydrophilic miscible non-aqueous solvent).”

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How broad are the claims for active ingredient identity: does stereochemistry matter for infringement?

Short answer: Yes. The claims require the exact stereochemically defined active, which can narrow infringement and strengthen defenses for products using different stereoisomers or different salt/ester forms.

Claim language lock-in

The API is not described generically as “the drug.” It is a specific stereochemical compound with a defined ester:

• carbamic acid tetrahydro-3-furanyl ester
• multiple stereocenters specified (3S and 3R(1R,2S*))

Infringement design-around pathways

Given this structure, a generic or reformulation effort could seek to:

• use a different stereoisomer mix, if supported by the marketed drug’s actual stereochemistry;
• use a different ester form (if an alternative synthetic series exists for the same pharmacology);
• use a different “water soluble tocopherol derivative” if the competitor avoids Vitamin E-TPGS and uses a non-equivalent tocopherol solubilizer outside the claim’s “water soluble tocopherol derivative” definition.

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What formulations are protected: tocopherol derivative and solvent system limitations

Short answer: Protected formulations are those where the tocopherol component is “water soluble” (with Vitamin E-TPGS as the explicit representative embodiment) and the non-aqueous hydrophilic solvent is miscible with that tocopherol derivative, typically PEG + propylene glycol, or PEG/propylene glycol/PVP.

Water soluble tocopherol derivative: “Vitamin E-TPGS” as the anchor

• Claim 4: “wherein the water soluble tocopherol derivative is Vitamin E-TPGS.”
• Claim 10: same concept.
• Claim 13/15/19/21: Vitamin E-TPGS appears as the tocopherol derivative in specific compositions.

Enforcement implication: If a product uses a different tocopherol TPGS-like molecule, parties will likely litigate:

• whether the alternative is still a “water soluble tocopherol derivative” under claim construction;
• whether miscibility and functional bioavailability outcomes establish equivalence.

Hydrophilic non-aqueous solvent: miscibility and selection set

• Claim 1: hydrophilic non-aqueous solvent miscible with the water soluble tocopherol derivative (functional miscibility requirement).
• Claim 7: polyethylene glycol + propylene glycol mixture.
• Claim 18: solvent is PEG, propylene glycol, PVP, or combinations.

Enforcement implication: Competitors that swap PEG/propylene glycol for less compatible solvents can try to avoid the “miscible” requirement or argue non-equivalent solvent selection.

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When does US 6,730,679 lose exclusivity: expiration timing and regulatory exclusivity mechanics?

Short answer: US formulation patents like US 6,730,679 generally expire based on filing/priority dates under US patent term rules, while regulatory exclusivities (data exclusivity, marketing exclusivity) can extend market protection independent of the patent.

No expiration date or priority/filing dates were provided in the prompt. Without the patent’s filing date (or priority) and without an asserted regulatory product link (NDA/ANDA/BLA), a precise exclusivity timeline cannot be produced.

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How strong is the “unexpectedly enhanced bioavailability” limitation for US 6,730,679 validity and claim construction?

Short answer: It is a high-friction element that can support validity but can also become a litigation pressure point because it ties claims to empirical performance.

Why it matters in US patent disputes

• If “unexpected” bioavailability is central to novelty/non-obviousness, the patent’s prosecution history and supporting examples will matter.
• In litigation, challengers can argue:
  • the effect is not truly unexpected given known TPGS/PEG absorption-enhancement literature;
  • the comparison baseline is wrong or data do not establish a clear unexpected effect across the full claim scope (all ratios, all dosage forms, all solvent variants);
  • the claim is drafted broadly enough that some embodiments may not deliver the effect.

How to read scope risk

• Independent claims include the performance phrase directly. That increases the chance that “not achieving unexpected bioavailability” can be used as a non-infringement or invalidity lever depending on claim construction approach.
• Dependent claims (like claim 21) that lock to a specific quantitative blend may be easier to defend as tied to demonstrated performance.

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How many patents cover this formulation concept: related patent estate and continuation risk?

Short answer: Not determinable from the information provided. The claim set alone does not establish:

• whether there are family members (WO, EP, JP, CN, IN),
• whether there are continuations/divisionals expanding to other dosage forms,
• whether there are later patents on manufacturing, process, or scale-up.

No patent publication numbers, applicants, or related US patents were provided.

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Which companies are likely affected: what generic entry risks exist for products with Vitamin E-TPGS/PEG systems?

Short answer: The claims read on any oral formulation of the specified stereochemically defined active that uses:

• Vitamin E-TPGS (or an arguable water soluble tocopherol derivative), plus
• PEG/propylene glycol or PEG/PVP-type miscible hydrophilic solvents,
• within the quantitative ranges (or at least within the ranges claimed in the asserted independent claims),
• and where the product is marketed as having unexpectedly enhanced bioavailability (or the formulation data support that attribute).

No NDA/ANDA holder, branded product name, or paragraph IV facts were provided, so the affected-company list cannot be constructed.

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What formulations are most likely to be found infringing: soft gelatin capsules vs solutions vs capsules

Short answer: Soft gelatin capsule embodiments are likely the most commercially relevant and likely to be easiest for plaintiffs to map against product labeling and composition submissions, because claim 12/14/20/21 explicitly cover soft gelatin capsules with Vitamin E-TPGS and PEG/propylene glycol.

Claim-to-dosage-form mapping

• Solution: claim 8 (and claim 1 broad composition supports solution indirectly)
• Capsule: claim 5
• Soft gelatin capsule: claims 12, 14, 20, 21
• Oral administration: claim 17 and claim 21

Litigation practicality: If an accused product is a softgel using the same blend ratios, infringement analysis becomes mostly compositional.

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How do the claim ratios constrain design-around: API-to-TPGS and percentage ranges

Short answer: Ratio constraints and percentage ranges provide both enforcement leverage and design-around opportunities.

Key quantitative anchors

• Claim 2: Vitamin E-TPGS ≥ 20%
• Claim 3: API:Vitamin E-TPGS ~1:0.5 to 1:3 w/w
• Claim 6: API dose ~10 to 1500 mg
• Claim 11: API (component a) + tocopherol derivative 10–60% w/w, and API:tocopherol ratio ~1:0.5 to 1:10 w/w
• Claim 18:
  • API 1–50% w/w
  • tocopherol derivative 10–60% w/w
  • hydrophilic solvent 15–95% w/w
  • solvent is PEG, propylene glycol, PVP, or combinations
• Claim 21: fixed percentages:
  • API 19%
  • Vitamin E-TPGS 51%
  • PEG 25%
  • propylene glycol 5%

Design-around: A competitor could attempt to move outside one or more:

• tocopherol percentage minimums (e.g., keep tocopherol below 10% if aiming to avoid claim 11/18, or below 20% to avoid claim 2),
• solvent selection set (avoid PEG/propylene glycol/PVP),
• miscibility pairing (use a solvent not miscible with the tocopherol derivative used).

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What about manufacturing method or process patents: does US 6,730,679 cover processes?

Short answer: The claim text provided is strictly composition-based (formulation). It does not present manufacturing step recitations.

Enforcement implication: If a competitor uses the same final composition but manufactures differently, US 6,730,679’s process coverage is likely not the hook; instead, the hook is the final product formulation composition.

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Does US 6,730,679 overlap with method-of-use, dosing, or therapeutic indication patents?

Short answer: The provided claims are formulation-only, not method-of-use for treating a disease, not dosing regimens, and not specific indication language.

Overlap risk: Overlap is likely limited to combination products if other patents cover:

• the API itself (drug substance),
• crystalline forms/polymorphs,
• dosing regimens,
• medical use.

No such related patents were provided.

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What is the Orange Book status of US 6,730,679?

Short answer: Not determinable from the prompt. Orange Book status requires mapping the patent to an NDA/ANDA product listing number and then checking listing type (drug substance vs drug product vs excipient), plus expiration and exclusivity codes.

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Key Takeaways

• US 6,730,679 protects a specific stereochemically defined API plus a water soluble tocopherol derivative (explicitly Vitamin E-TPGS) plus a miscible hydrophilic non-aqueous solvent system (explicitly PEG and propylene glycol, and broadly PEG/propylene glycol/PVP).
• The claims include quantitative range constraints and dosage forms (solution, capsule, soft gelatin capsule), with a particularly concrete softgel formulation in claim 21.
• The “unexpectedly enhanced bioavailability” limitation is a central claim attribute that can drive both validity and claim construction fights.
• A precise expiration/exclusivity timetable and the identity of likely litigants require external identifiers (filing/priority date, product mapping to Orange Book, and patent family members). Those inputs were not provided.

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FAQs

1. Does US 6,730,679 require Vitamin E-TPGS specifically to infringe?
   Claim 1 uses the broader phrase “water soluble tocopherol derivative,” while dependent claims identify Vitamin E-TPGS. Infringement depends on the accused product’s tocopherol derivative and whether it falls within “water soluble tocopherol derivative” under claim construction.

2. Can a soft gelatin capsule avoid infringement by changing only the solvent system?
   Likely not if the alternative solvent is still a hydrophilic non-aqueous solvent miscible with the tocopherol derivative and falls within the claimed solvent selection set and ratio/percentage limits.

3. Is the bioavailability performance requirement a product attribute or a testable limitation?
   The claims tie “unexpectedly enhanced bioavailability” directly to the claimed formulations, which can make it testable in litigation through product formulation comparisons and supporting evidence.

4. What parts of the claim are easiest to map in infringement: amounts, dosage form, or stereochemistry?
   Dosage form and compositional percentages are typically easiest to map from product specs or regulatory submissions; stereochemistry is harder but can be decisive if the accused API differs.

5. Is US 6,730,679 a formulation patent only, or does it also cover methods of making?
   Based on the provided claim text, it is composition-focused and does not recite manufacturing steps.

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References

1. US Patent 6,730,679 (claims provided in prompt).

Drugs Protected by US Patent 6,730,679

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 6,730,679

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	1150
African Regional IP Organization (ARIPO)	9801343
Argentina	006345
Austria	230602
Australia	2159197