Details for Patent: 6,262,022

Summary for Patent: 6,262,022

Title:	Pharmaceutical compositions containing cyclosporin as the active agent
Abstract:	Pharmaceutical compositions comprising a cyclosporin in a novel galenic formulations for oral administration. The compositions typically comprise a cyclosporin, 1,2-propylene glycol, a mixed mono-, di- and tri-glyceride and a hydrophilic surfactant. Further a refined glycerol-transesterified corn oil is provided representing a mixed mono-, di- and tri-glyceride suitable for the novel formulation. Dosage forms include in particular oral dosage forms.
Inventor(s):	Birgit Hauer, Armin Meinzer, Ulrich Posanski, Jacky Vonderscher
Assignee:	Novartis AG
Application Number:	US09/488,215
Patent Claim Types: see list of patent claims	Composition; Dosage form;

Executive summary: US Patent 6,262,022 covers cyclosporin (cyclosporine) oral/pharmaceutical compositions formulated with a specific lipid blend dominated by linoleic/oleic mono-, di- and triglycerides plus 1,2-propylene glycol and a surfactant (including castor oil ethoxylate-type with HLB ≥10). Claim coverage is driven by the carrier medium definition and multiple quantitative/functional constraints (fatty-acid dominance, ≥85% content of the triglyceride fraction, low free glycerol, surfactant HLB and chemistry). In US, this patent is a composition-of-matter style claim set, so infringement analysis will focus on whether a marketed cyclosporine product uses the same carrier components within the same constraints rather than on downstream manufacturing steps alone.

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What is US Patent 6,262,022 and what does it claim for cyclosporin formulations?

Core invention (as claimed): A pharmaceutical composition where cyclosporin is the active agent in a defined carrier medium consisting of:

• 1,2-propylene glycol
• a mixture of C12-20 fatty acid mono-, di-, and tri-glycerides predominantly comprising linolenic acid, linoleic acid, and oleic acid mono-, di-, and tri-glycerides
• a surfactant
  with numerous dependent claim tightenings (dominant linoleic/oleic split, transesterification origin (corn oil and glycerol), ≥85% of the whole composition being the fatty-glyceride mixture, low free glycerol (<1 wt%), and surfactant HLB ≥10 plus castor oil + ethylene oxide reaction product).

Claim 1 is the “bread-and-butter” coverage anchor

Claim 1 sets the infringement perimeter: the accused product must be a cyclosporin pharmaceutical composition having all carrier-medium elements and meeting the “predominantly comprises” constraint for the fatty-glyceride mixture plus the presence of a surfactant.

Key structural limitations in Claim 1:

• Active: “cyclosporin as an active agent” (no strength or dose specified in the claim set you provided)
• Carrier medium must comprise:
  • (a) 1,2-propylene glycol
  • (b) mixture of C12-20 fatty acid mono-/di-/tri-glycerides “predominantly” comprising linolenic, linoleic, oleic mono-/di-/tri-glycerides
  • (c) a surfactant

Practical implication: if a cyclosporine oral product substitutes a different cosolvent (e.g., polyethylene glycol-based carrier) or does not include 1,2-propylene glycol, it may fall outside Claim 1 even if it uses lipid excipients. Conversely, if it includes 1,2-propylene glycol, a lipid blend matching the fatty-glyceride profile, and a surfactant, it becomes a candidate for Claim 1 infringement analysis.

Dependent claims add hard numeric/chemical qualifiers

Dependent claims narrow Claim 1 along three axes:

1. fatty acid profile and proportion
2. lipid provenance and processing (corn oil/glycerol transesterification; treated to yield a high fraction of linoleic/oleic glycerides)
3. surfactant identity and HLB property
4. impurity control (free glycerol)
5. dosage form (gelatin capsule)
6. optional additive (ethanol)

Fatty-glyceride profile tightening

• Claim 2: component (b) predominantly comprises linoleic acid and oleic acid mono-/di-/tri-glycerides (tightens away from linolenic or at least reduces its relative role vs Claim 1).
• Claim 3: component (b) is a transesterification product (functional origin limitation).
• Claim 4: transesterification product specifically from corn oil and glycerol.
• Claim 5: component (b) comprises linoleic + oleic mono-/di-/tri-glycerides in an amount ≥85% of the “whole composition.”
  This is a major infringement lever: many formulations will have lipid excipients well below this level depending on total excipient and solvent content.
• Claim 6: the product is from corn oil and glycerol and treated so that the linoleic/oleic mono-/di-/tri-glycerides are present at ≥85% of the whole composition.

Low free glycerol control

• Claim 7: free glycerol content is <1 percent by weight relative to “free glycerol plus mono-, di- and tri-glycerides.”
  This targets processing/excipient purification. Even if the triglyceride blend matches fatty-acid dominance, a product with higher free glycerol could avoid this dependent claim.

Surfactant identity and HLB threshold

• Claim 8: surfactant has HLB ≥10.
• Claim 9: surfactant comprises a reaction product of natural or hydrogenated castor oil and ethylene oxide.
  This is a high-specificity chemical limitation. If a cyclosporine product uses a different surfactant system (even with HLB ≥10), it may avoid Claim 9 but still potentially fall under Claim 8 (if HLB requirement is met) and Claim 1 (if surfactant is present without identity constraints).

Optional additions / dosage form

• Claim 10: carrier medium additionally comprises a hydrophilic phase co-component.
• Claim 11: composition further comprises ethanol.
• Claim 12: encapsulated in a gelatin capsule.

These dependents expand cover for common excipient practices. But as a matter of infringement, they require the additional features be present.

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What is the scope of protection: how broad is Claim 1 vs the dependent claims?

Claim 1 breadth: Medium-to-broad for formulation space because it does not specify exact amounts for each component (other than “predominantly” for fatty-glycerides and presence of propylene glycol and surfactant). However, it is still narrowed by the combined excipient structure:

• specific cosolvent (propylene glycol)
• specific lipid class (C12-20 fatty mono/di/tri glycerides)
• specific fatty acid composition (“predominantly” linolenic/linoleic/oleic)
• surfactant presence (not identity)

Dependent claims are substantially narrower and can carve out large sections of competing cyclosporine formulation space:

• ≥85% of whole composition being linoleic/oleic mono/di/tri glycerides (Claims 5 and 6)
• specific feedstock and process (corn oil + glycerol transesterification) (Claims 4 and 6)
• low free glycerol (<1 wt% by the specified basis) (Claim 7)
• specific surfactant chemistry (castor oil/ethylene oxide reaction product) (Claim 9)

Infringement mapping logic for product teams

1. Identify whether the marketed product contains cyclosporin and is formulated with 1,2-propylene glycol.
2. Confirm whether the lipid carrier includes a mixture of C12-20 fatty acid mono-/di-/tri-glycerides.
3. Determine whether the fatty acid profile is predominantly linolenic/linoleic/oleic (Claim 1) and specifically linoleic/oleic (Claim 2).
4. If the product’s lipid mixture is “mostly” linoleic/oleic and is used at very high proportion (≥85% of total formulation), Claims 5/6 become relevant.
5. If excipient manufacturing data indicates transesterification from corn oil and glycerol, Claims 3/4/6 become relevant.
6. If analytical impurity specs show free glycerol <1% on the given basis, Claim 7 becomes relevant.
7. For surfactants, compare HLB and chemistry: castor oil ethoxylate (Claim 9) is a direct qualifier.

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Which US cyclosporin products are most likely to fall within the patent’s carrier-medium definition?

You provided only the claim text, not the Orange Book, FDA listing, or competitor formulation compositions. Without that, the only defensible scope conclusion is structural: products using a lipid-based cyclosporin oral formulation with propylene glycol and a surfactant system, plus glyceride composition dominated by linoleic/oleic fatty acids, are the closest to Claim 1. Products using different cosolvents (e.g., ethanol-only, PEG-based systems) or different surfactant chemistries could still meet Claim 1 if they include a surfactant of unspecified type, but may miss Claims 9 and 8 depending on HLB and identity.

Commercial formulation comparisons should be built around:

• excipient list (propylene glycol presence)
• glyceride class and fatty acid distribution
• proportion of glyceride fraction
• free glycerol specification
• surfactant chemistry and HLB

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How do the claim qualifiers impact design-around strategies for generic or reformulated cyclosporin products?

1) Avoid 1,2-propylene glycol

Removing or replacing 1,2-propylene glycol is the cleanest design-around against Claim 1, since it is required as component (a).

2) Use a different lipid carrier species or fatty-acid distribution

Even if propylene glycol and surfactant are present, Claim 1 requires a mixture of C12-20 fatty mono/di/tri-glycerides “predominantly” containing linolenic/linoleic/oleic fatty acids. Shifting to a different glyceride profile (e.g., more saturated fatty glycerides or different dominant unsaturates) reduces likelihood of satisfying “predominantly comprises.”

3) Break the “≥85% of whole composition” threshold

Claims 5/6 require the linoleic/oleic mono/di/tri glycerides to be ≥85% of the whole composition, a very high bar. Many practical formulations would not reach that ratio because total composition includes surfactant and propylene glycol (and possibly hydrophilic co-components and ethanol).

4) Avoid transesterification from corn oil and glycerol (or avoid the functional “transesterification product” condition)

Claims 3/4/6 include process origin. A different manufacturing route for the lipid fraction can avoid those dependents even if the final fatty-acid profile matches.

5) Raise free glycerol above the <1% threshold

Claim 7 is a processing/purification and impurity control qualifier. If the relevant glyceride fraction contains free glycerol above the defined basis, it can avoid Claim 7.

6) Use a different surfactant chemistry or HLB profile

• Claim 8: HLB ≥10. If the surfactant system uses HLB below that threshold, it avoids Claim 8.
• Claim 9: reaction product of castor oil (natural or hydrogenated) + ethylene oxide. Using a different surfactant chemistry may avoid Claim 9 even if HLB remains ≥10.

7) Dosage form swap

Claim 12 is capsule-specific. If the product is not encapsulated in a gelatin capsule (e.g., different enclosure system), it may avoid Claim 12 while still potentially meeting Claim 1 and other dependents.

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What patent landscape questions can be answered from the claim set alone?

Given only the claim text and not prosecution history, listed assignees, family members, or related patents, the landscape must be framed by claim architecture:

How many separate technical “inventions” are in the claim set?

At least four:

1. lipid blend definition (C12-20 mono/di/tri glycerides dominated by specified fatty acids)
2. process origin (transesterification, including corn oil + glycerol)
3. impurity control (free glycerol constraint)
4. surfactant constraints (HLB threshold and castor oil/ethylene oxide reaction product)

In litigation or licensing terms, this indicates potential for:

• argument about whether the competitor’s excipient profile meets “predominantly comprises” and “≥85%” (Claims 1, 2, 5, 6)
• argument about whether the competitor’s lipid fraction is actually a transesterification product (Claims 3/4/6)
• argument about analytic impurity levels of free glycerol (Claim 7)
• argument about surfactant selection (Claims 8/9)

Where are the highest-risk claim points for challengers?

• “predominantly comprises” fatty-acid dominance (Claim 1/2) because it invites formulation analytics and expert interpretation.
• the “≥85% of whole composition” limit (Claims 5/6) because it is both measurable and central.
• the surfactant chemistry (Claim 9) because it provides a crisp identity filter.

What is the strongest claim for plaintiffs?

Claim 1 is strongest when a competitor product uses the same general carrier architecture (propylene glycol + glyceride fraction dominated by linoleic/oleic species + surfactant). Claim 9 and Claim 7 become strongest fallback targets if the accused formulation uses castor oil ethoxylates and has low free glycerol.

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Key takeaways

• US Patent 6,262,022 protects cyclosporin pharmaceutical compositions defined by a specific carrier medium: 1,2-propylene glycol + C12-20 fatty mono/di/tri glycerides dominated by linolenic/linoleic/oleic + a surfactant.
• Dependent claims add high-friction constraints: ≥85% linoleic/oleic glycerides (Claims 5/6), corn oil + glycerol transesterification (Claims 4/6), free glycerol <1% by the specified basis (Claim 7), and castor oil/ethylene oxide surfactant with HLB ≥10 (Claims 8/9).
• For design-around, the most direct levers are removing propylene glycol, shifting the fatty-glyceride profile, missing the ≥85% proportion, changing the lipid synthesis route, changing free glycerol levels, and using a different surfactant chemistry/HLB.

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FAQs

1. What does “predominantly comprises” mean in Claim 1 for the fatty-glyceride mixture?
   It is a qualitative dominance requirement tied to the linolenic/linoleic/oleic mono/di/tri glycerides in the C12-20 glyceride mixture; infringement will turn on analytical characterization of that mixture in the accused formulation.

2. How does the “≥85% of the whole composition” limitation affect generic formulation risk?
   It is a high quantitative threshold tied to the linoleic/oleic mono/di/tri glycerides fraction relative to the total composition, so many competing excipient systems may not meet it even if they match the fatty-acid profile.

3. Can a formulation infringe Claim 1 but avoid Claims 5 and 6?
   Yes. If it meets Claim 1’s general glyceride dominance but uses the glyceride fraction at less than the ≥85% proportion of the whole composition, it can avoid Claims 5/6.

4. What surfactant systems are targeted by Claim 9?
   The claim targets surfactants that are reaction products of natural or hydrogenated castor oil and ethylene oxide, and Claim 8 adds the HLB ≥10 constraint.

5. If a product is not in a gelatin capsule, can it still infringe?
   It can. Claim 12 is capsule-specific, but Claim 1 is not. Avoiding gelatin capsules only addresses Claim 12 unless other dependents incorporate dosage-form requirements.

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References (APA)

No sources were provided or cited in the prompt text.

Drugs Protected by US Patent 6,262,022

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 6,262,022

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	403436
Austria	A129892
Australia	1852792
Australia	659460
Canada	2072509