Details for Patent: 6,248,363

Summary for Patent: 6,248,363

Title:	Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
Abstract:	The present invention provides solid pharmaceutical compositions for improved delivery of a wide variety of pharmaceutical active ingredients contained therein or separately administered. In one embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier including a substrate and an encapsulation coat on the substrate. The encapsulation coat can include different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides. In another embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier being formed of different combinations of pharmaceutical active ingredients, hydrophilic surfactants, lipophilic surfactants and triglycerides. The compositions of the present invention can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients, such as drugs, nutrionals, cosmeceuticals and diagnostic agents.
Inventor(s):	Mahesh V. Patel, Feng-Jing Chen
Assignee:	Spriaso LLC
Application Number:	US09/447,690
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,248,363
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Dosage form;

Patent 6,248,363 Landscape: Scope and Claim Construction for Hydrophilic Actives Solubilized in Encapsulation Coats Using Hydrophilic Surfactants Plus Lipophilic Additives

What does US Patent 6,248,363 claim: solid carriers with an encapsulation coat that solubilize hydrophilic actives

Core answer: US 6,248,363 claims pharmaceutical solid carriers whose coat (or the carrier itself, in an alternative embodiment) contains (i) a hydrophilic therapeutic active plus (ii) a hydrophilic surfactant in an amount that partially or fully solubilizes the active within the coat, plus (iii) a lipophilic additive selected from defined classes (lipophilic surfactants, triglycerides, or combinations). The claims are drafted broadly across active types, surfactant chemistry, lipophilic additive classes, and many dosage-form and delivery categories.

Claim 1: “encapsulation coat” composition that solubilizes hydrophilic actives

Claim 1 is the anchor independent claim and defines the most central limitation set:

1. Dosage form architecture

   • “A pharmaceutical composition in the form of a solid carrier comprising a substrate and an encapsulation coat on the substrate.”

2. Coat composition

   • Coat includes:
     • a hydrophilic pharmaceutical active ingredient (“therapeutically effective amount”)
     • an effective solubilizing amount of at least one hydrophilic surfactant
     • a lipophilic additive selected from:
       • lipophilic surfactants
       • triglycerides
       • combinations

3. Functional solubilization limitation

   • The hydrophilic surfactant amount must be “an amount effective to partially or fully solubilize the pharmaceutical active ingredient in the encapsulation coat.”

Claim 6: functional solubilization in the solid carrier system (alternative architecture)

Claim 6 parallels Claim 1 but removes the “encapsulation coat” requirement and instead states the solid carrier contains the admixture such that solubilization occurs “in the solid carrier.”

Key change:

• Claim 1 requires “encapsulation coat on the substrate.”
• Claim 6 frames the same solubilization concept at the solid carrier level.

Claims 2, 10, 34, 36: active ingredient breadth

These claims broaden the active ingredient universe to:

• drugs, nutrients, cosmeceuticals, diagnostic agents
• salts, isomers, derivatives, mixtures
• special inclusion lists for hydrophilic classes (peptides, proteins, antibodies, vaccines, nucleic acids, etc.)

The legal effect is broad subject-matter coverage: the solubilization-coat concept is not limited to small molecules.

Claims 3, 5, 7, 57: quantitative formulation ratios

The claims introduce numerical ranges that can materially narrow infringement for some designs while remaining permissive for many others.

• Lipophilic additive : hydrophilic surfactant weight ratio
  • Claims 3 and 7: approximately 0.10:1 to 0.92:1
• Active loading in the coat / carrier
  • Claim 4 and Claim 5: active represents approximately 1.96 wt.% to 28.57 wt.% of the encapsulation coat
  • Claim 8: active represents approximately 4.6 wt.% to 50.0 wt.% of the solid carrier
  • Claim 57: active represents approximately 4.6 wt.% to 50.0 wt.% of the solid carrier (dependency confirmation)

Claims 9, 35: hydrophilicity threshold

• Claim 9 and Claim 35 require the hydrophilic active has “apparent water solubility of at least about 1 mg/mL.”

This can matter for infringement because it is an explicit physicochemical criterion.

What is the claim scope on surfactants and lipophilic additives

Core answer: The patent claims solubilization using hydrophilic surfactants (non-ionic or ionic), paired with defined lipophilic additives (lipophilic surfactants or triglycerides). The surfactant selection is driven by class membership and, for non-ionic surfactants, an HLB floor.

Non-ionic hydrophilic surfactants (Claims 15, 41, 16, 42)

• Non-ionic hydrophilic surfactant with HLB ≥ 10.
• Exemplary enumerated non-ionic surfactants include:
  • alkylglucosides, alkylmaltosides, alkylthioglucosides
  • lauryl macrogolglycerides
  • polyoxyethylene alkyl ethers/alkylphenols
  • polyethylene glycol fatty acid esters/glycerol fatty acid esters
  • polyoxyethylene sorbitan fatty acid esters
  • polyoxyethylene-polyoxypropylene block copolymers
  • polyoxyethylene vegetable oils and hydrogenated variants
  • tocopherol polyethylene glycol succinates
  • sugar esters/ethers, sucroglycerides, reaction mixtures

Ionic hydrophilic surfactants (Claims 17, 43, 18, 44)

Enumerated ionic classes include:

• alkyl ammonium salts
• bile acids and salts
• amino acid/carnitine/peptide-polypeptide fatty acid derivatives
• acyl lactylates
• tartaric esters of mono-/diglycerides (diacetylated tartaric acid esters)
• succinylated monoglycerides, citric acid esters of mono-/diglycerides
• alginate salts and propylene glycol alginate
• lecithins and hydrogenated lecithins, lysolecithins and hydrogenated variants
• lysophospholipids/phospholipids and derivatives
• alkylsulfate salts; fatty acid salts
• sodium docusate

Lipophilic additive classes (Claims 24-26 and 47-49)

• Claim 1 permits lipophilic additive as either:
  • lipophilic surfactants
  • triglycerides
  • combinations
• Dependent claim coverage narrows:
  • Claims 24 and 47: lipophilic additive selected from lipophilic surfactants
  • Claims 26 and 49: lipophilic additive is triglyceride

Triglycerides are defined broadly to include vegetable oils, fish oils, animal fats, hydrogenated/partially hydrogenated, synthetic/modified/fractionated triglycerides and mixtures.

What is claimed about the solid carrier, substrate, and coating formats

Core answer: The patent discloses extensive generic carrier form language: powder/substrate plus multiparticulate formats, including beads, pellets, microspheres/nanospheres, tablets/capsules, and many coating modes (enteric, barrier, enzyme-degradable, fast disintegration, etc.). This broad format coverage increases design-around difficulty at the “dosage form” level, but infringement still depends on the coat/carrier solubilization architecture and ratio/loading constraints.

Substrate and multiparticulate definitions (Claims 19-22)

• Claim 19: substrate is powder or multiparticulate
• Claim 20-21: substrate can be additive, active ingredient, or mixture; additives include typical formulation excipient functional categories (binders, buffers, disintegrants, binders, flavors, resins, plasticizers, preservatives, solvents, sweeteners, thickeners, etc.)
• Claim 22: multiparticulate types including granule, pellet, bead, spherule, microcapsule/microsphere and also tablet/capsule at the multiparticulate dependency layer.

Solid carrier geometric/format list (Claim 23 and Claim 45)

• Claim 23: bead, beadlet, granule, spherule, pellet, microcapsule, microsphere, nanosphere, film, wafer, sprinkle, implant, troche/lozenge, platelet, nanocapsule, strip.
• Claim 45: essentially the same but without some omissions.

Coating and process options (Claims 27-28 and 50-51)

• Claim 27: enteric coated; fast disintegration coated; seal coated; film coated; barrier coated; compress coated; enzyme-degradable coating.
• Claim 28: encapsulated, extruded, compressed, pelletized, coated, mixed granulated, crystallized, lyophilized, molded.
• Claim 50 and Claim 51: repeats these within the Claim 6 path.

Dosage forms and delivery categories (Claims 29-31 and 52-54)

• Claim 29/52: capsule, tablet, ovule, suppository, film wafer, chewable, buccal, sublingual, quick-dissolved, effervescent, granule, pellet, bead, pill, sachet, sprinkle, dry syrup, reconstitutable solid, suspension, lozenge, troche, implant, powder, triturate, platelet, strip.
• Claim 30/53: immediate, pulsatile, controlled, extended, delayed, targeted, targeted delayed release.
• Claim 31/54: oral, nasal, ocular, urethral, buccal, transmucosal, vaginal, topical, rectal.

What is claimed about “hydrophilic active solubility” and active class coverage

Core answer: The only explicit physicochemical constraint is the apparent water solubility ≥ 1 mg/mL limitation in dependent form (Claims 9 and 35). The independent claims do not include this numerical threshold, so the landscape turns on whether a challenger can get around by arguing a given active does not satisfy the “hydrophilic active ingredient” or does not satisfy the solubilization-in-coat functionality.

Hydrophilic active classes (Claims 10, 36)

Claims 10 and 36 list high-level biologics and macromolecules:

• cytokines, peptidomimetics, peptides, proteins, toxoids, serum, antibodies, vaccines
• nucleosides/nucleotides, portion of genetic material, nucleic acids

Therapeutic-area enumerations (Claims 11, 37, 12-14 variants)

The claims list extensive therapeutic categories and also enumerate large sets of specific drug names. That style is typical of broad claim drafting that can help assertion across a wide range of candidates.

Method-of-administration scope: what acts are claimed

Core answer: The patent includes a method claim that simply administers the dosage form:

• Claim 32: “administering to the mammal a dosage form of the pharmaceutical composition of claim 1.”
• Claim 33: mammal is human.
• Claim 55-56: same structure tied to Claim 6.

This creates enforcement hooks for both product makers and downstream users, but infringement still hinges on having the claimed composition.

How strong is infringement risk under the numeric constraints

Core answer: The patent includes three main numeric tripwires that can narrow the literal scope for certain designs:

1. Lipophilic additive : hydrophilic surfactant ratio of ~0.10:1 to ~0.92:1 (Claims 3/7).
2. Active loading window in the coat/carrier (Claims 4/5/8/57).
3. Hydrophilic active apparent solubility ≥ 1 mg/mL (Claims 9/35).

Literal infringement pressure points

• If a formulation uses hydrophilic surfactant for solubilization but uses a lipophilic additive outside the ratio range, it may avoid those dependent claim limitations.
• If a competitor uses much higher or lower active loading, it may exit the dependent quantitative windows.
• If a competitor’s selected active is below 1 mg/mL apparent solubility, it may avoid the solubility-dependent coverage.

Independent claim “escape routes”

Even with those dependent constraints, Claims 1 and 6 remain broad because they require:

• solid carrier with substrate plus encapsulation coat (Claim 1) OR solid carrier admixture system (Claim 6)
• inclusion of hydrophilic active + hydrophilic surfactant in effective solubilizing amount
• lipophilic additive selected from lipophilic surfactants and/or triglycerides
• functional solubilization “in the encapsulation coat” (Claim 1) or “in the solid carrier” (Claim 6)

Designs that do not achieve solubilization “in” the claimed physical locus may be arguable for non-infringement, even if the surfactant system improves overall dissolution.

Which formulation design patterns map most closely to the claim

Core answer: The claim best matches “self-solubilizing” solid dosage particles where hydrophilic actives are incorporated into a surfactant/lipophilic phase that retains solubilization capacity at the coat/carrier level.

High alignment: likely within-claim product architectures

• Layered beads or granules with:
  • hydrophilic surfactant in the coat
  • lipophilic triglyceride or lipophilic surfactant
  • hydrophilic active present in the coat, aiming for partial/full solubilization in the coat
• Nanosphere/microsphere/microcapsule solid carriers with:
  • embedded hydrophilic active plus hydrophilic surfactant
  • lipophilic triglyceride phase
  • targeted release formats that still preserve coat microenvironment solubilization

Lower alignment: typical design divergences

• If the lipophilic additive is present but not triglyceride or lipophilic surfactant (outside the claim-defined group), dependent claims may be avoided.
• If the active is outside the “hydrophilic active ingredient” concept (as used by the patent) or is not solubilized within the coat/solid carrier microenvironment, functional limitation issues arise.

What matters for FDA Orange Book and Paragraph IV strategy

Core answer: Patent-enforcement and exclusivity risk cannot be tied to FDA status, listing, or Orange Book expiration solely from the claim text. Without the FDA listing mapping (drug product(s), dosage form(s), and patent coverage entries), the litigation and entry timeline exposure cannot be accurately assessed.

Patent landscape completeness limits

Critical issue: You provided the claim set but not the patent bibliographic data (assignee, filing/grant dates, continuations/divisionals), nor any cross-references to the patent’s specification basis. Without that, a complete landscape of:

• related family members
• earlier priority art and document citations
• prosecution history (claim amendments, narrowing/estoppel)
• asserted/waived embodiments
• real-world litigation posture cannot be produced from claim text alone.

What US 6,248,363 covers in practice (actionable claim-to-design mapping)

In-scope formulation elements checklist

To be inside the core scope of Claim 1 / Claim 6, a solid dosage product typically needs all of the following:

1. Solid carrier with substrate and (for Claim 1) an encapsulation coat on the substrate.
2. Hydrophilic active (therapeutically effective amount).
3. At least one hydrophilic surfactant present at an amount effective to partially or fully solubilize the active in the coat (Claim 1) or in the solid carrier (Claim 6).
4. Lipophilic additive selected from lipophilic surfactants and/or triglycerides.
5. (For dependent claim coverage) ratio and loading ranges, and optionally hydrophilic active solubility threshold.

Key claim construction phrases for enforcement

• “effective solubilizing amount”
• “partially or fully solubilize the pharmaceutical active ingredient in the encapsulation coat”
• “hydrophilic pharmaceutical active ingredient”
• the defined lipophilic additive group (lipophilic surfactants, triglycerides)
• “solid carrier” and “encapsulation coat on the substrate”

Key Takeaways

• US 6,248,363 is a formulation patent focused on solid carriers that use hydrophilic surfactants, plus a defined lipophilic additive class (lipophilic surfactants and/or triglycerides), to solubilize hydrophilic actives at the coat/solid-carrier level.
• The broadest coverage is in Claim 1 (coat-on-substrate architecture) and Claim 6 (solid-carrier admixture architecture), with dependent claims adding ratio and loading windows and a hydrophilic solubility threshold.
• Non-ionic surfactants with HLB ≥ 10 and a wide set of ionic surfactants are explicitly enumerated, increasing coverage across many excipient selections.
• Practical infringement risk turns on whether the accused formulation achieves solubilization in the specified locus (coat or carrier) and whether key dependent ratio/loading/solubility constraints are met.
• FDA/Orange Book, expiration, and litigation landscape cannot be determined from claim text alone.

FAQs

1. Does US 6,248,363 require the active to be solubilized in the final dosage form or only inside the coat/carrier?
   The claims use the functional limitation tied to “in the encapsulation coat” (Claim 1) or “in the solid carrier” (Claim 6).

2. Is the triglyceride component mandatory for infringement?
   Only if it’s part of the chosen lipophilic additive. The claim permits the lipophilic additive to be lipophilic surfactants, triglycerides, or combinations.

3. Can a formulation avoid dependent claim coverage by changing the surfactant-to-lipophilic additive ratio?
   Dependent claims 3 and 7 specify a ratio window; moving outside it can avoid those dependent limitations, but it does not necessarily avoid independent-claim coverage.

4. What surfactant types are explicitly allowed?
   Both non-ionic (with HLB ≥ 10) and ionic hydrophilic surfactants are enumerated in dependent claims.

5. Are biologics and nucleic-acid therapeutics covered?
   The dependent claim sets list peptides, proteins, antibodies, vaccines, nucleic acids, and related hydrophilic categories.

References (APA)

1. United States Patent No. 6,248,363.

Drugs Protected by US Patent 6,248,363

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 6,248,363

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	537812
Australia	1670102
Australia	1798101
Australia	2002243387