Details for Patent: 8,648,048

Summary for Patent: 8,648,048

Title:	Methods of providing therapeutic effects using cyclosporin components
Abstract:	Methods of treating an eye of a human or animal include administering to an eye of a human or animal a composition in the form of an emulsion including water, a hydrophobic component and a cyclosporin component in a therapeutically effective amount of less than 0.1% by weight of the composition. The weight ratio of the cyclosporin component to the hydrophobic component is less than 0.8.
Inventor(s):	Andrew Acheampong, Diane D. Tang-Liu, James N. Chang, David F. Power
Assignee:	Saint Regis Mohawk Tribe
Application Number:	US13/967,168
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,648,048
Patent Claim Types: see list of patent claims	Use;

Scope and claims of US Patent 8,648,048 and the U.S. patent landscape for cyclosporin A topical ophthalmic emulsions (tear production / keratoconjunctivitis sicca)

US 8,648,048 is a process-and-formulation method patent that claims a specific twice-daily topical ophthalmic emulsion containing cyclosporin A at ~0.05% by weight plus a defined excipient set: castor oil (~1.25%), polysorbate 80 (~1.0%), acrylate/C10-30 alkyl acrylate cross-polymer (~0.05%), and (in dependent claims / the independent claims where recited) glycerine (~2.2%) and a sodium hydroxide buffer, with an emulsion pH of about 7.2 to about 7.6. The claims further require functional outcomes (increase tear production; treat keratoconjunctivitis sicca; reduce adverse events vs. a comparator emulsion) and include a blood-exposure limitation (substantially no detectable cyclosporin A).

What does US 8,648,048 claim for cyclosporin A tear production and dry eye treatment?

Answer: It claims twice-daily topical administration of a cyclosporin A emulsion with tightly bounded concentrations and excipient components, plus performance requirements tied to tear production and therapeutic efficacy in keratoconjunctivitis sicca. It also claims low systemic exposure (no detectable blood cyclosporin A) and includes comparator-based dependent claims on adverse events and visual distortion.

Claim set structure (independent vs. dependent)

• Independent methods

  • Claim 1: Increasing tear production by topical administration at twice a day of an emulsion comprising:
    • Cyclosporin A ~0.05% w/w
    • Polysorbate 80
    • Acrylate/C10-30 alkyl acrylate cross-polymer
    • Water
    • Castor oil ~1.25% w/w
    • Functional requirement: “effective in increasing tear production”
  • Claim 18: Treating keratoconjunctivitis sicca by twice-daily topical administration of an emulsion with specified ranges and components:
    • Cyclosporin A ~0.05% w/w
    • Castor oil ~1.25% w/w
    • Polysorbate 80 ~1.0% w/w
    • Acrylate/C10-30 alkyl acrylate cross-polymer ~0.05% w/w
    • Tonicity or demulcent component ~2.2% w/w
    • Buffer
    • Water
    • pH about 7.2 to about 7.6
    • Functional requirement: “effective in treating keratoconjunctivitis sicca”

• Independent-like compound content method

  • Claim 22: Administering a specified emulsion with concrete excipient amounts (including glycerine ~2.2% w/w and sodium hydroxide with water) twice daily to increase tear production, with the same cyclosporin A and excipient amounts and a functional requirement.

• Dependent claims adding specific excipient identities and conditions

  • Claims 2-6: Add tonicity/demulcent and/or buffer; specify glycerine and sodium hydroxide.
  • Claims 7-10: Lock polysorbate 80 and cross-polymer amounts; lock glycerine and sodium hydroxide.
  • Claims 11, 21: Low systemic exposure: “substantially no detectable concentration of cyclosporin A” in blood when administered in an effective amount.
  • Claims 12, 23: pH range 7.2–7.6.
  • Claims 13-16: Comparator-based effectiveness and performance:
    • “substantially as therapeutically effective as” or “at least as much therapeutic effectiveness as” a “second emulsion” dosed twice daily with cytosporin A 0.1% w/w and castor oil 1.25% w/w
    • includes reduced vision distortion when the emulsion “breaks down more quickly” in the eye than a comparator containing “only 50% as much castor oil”
    • includes reduction in adverse events vs. the comparator emulsion with cytosporin A 0.1% w/w and castor oil 1.25% w/w
  • Claim 17: adverse events are “side effects.”

What specific components and concentration limits matter most?

The claims are built around a core set of excipients that define the emulsion’s physical behavior and tolerability:

• Active: cyclosporin A at ~0.05% w/w
• Oil phase / lipid: castor oil at ~1.25% w/w
• Surfactant: polysorbate 80 at ~1.0% w/w (explicit in claim 7 and in claim 18; not given as a number in claim 1 but polysorbate 80 is still required)
• Thickener / gelling polymer: acrylate/C10-30 alkyl acrylate cross-polymer at ~0.05% w/w
• Tonicity/demulcent: glycerine at ~2.2% w/w
• Buffer: sodium hydroxide
• pH: 7.2 to 7.6
• Delivery regimen: twice a day
• Systemic exposure: no detectable cyclosporin A in blood

From an infringement-engineering perspective, the claims create three “must-have” clusters:

1. Composition cluster: cyclosporin A level plus the defined excipient set and (in several claims) their explicit concentrations.
2. Condition cluster: pH and buffer identity (sodium hydroxide) and glycerine presence.
3. Outcome cluster: tear production / keratoconjunctivitis sicca efficacy, low blood cyclosporin A, and comparator-based performance in some dependent claims.

How broad are the claims: what variants would still read on US 8,648,048?

Answer: The patent is medium-to-narrow in chemical scope because cyclosporin A is fixed at about 0.05% and the emulsion must include multiple specific ingredients. It is broader in that some excipient items can be optional via dependent claims (e.g., tonicity/demulcent identity, buffer presence) but the independent claims still require the defined core emulsion components and the twice-daily regimen.

Composition flexibility vs. hard requirements

• Claim 1 (tear production)

  • Requires cyclosporin A (~0.05%), castor oil (~1.25%), polysorbate 80, and the acrylate/C10-30 alkyl acrylate cross-polymer, plus water.
  • Does not in the claim text as provided force glycerine or sodium hydroxide for Claim 1, but dependent claims do.
  • Allows additional tonicity/demulcent component and/or buffer.

• Claim 18 (treat keratoconjunctivitis sicca)

  • Requires toner/demulcent component at ~2.2%, buffer, and pH 7.2–7.6.
  • This is closer to a formulation “locked” claim because it also specifies polysorbate 80 amount and cross-polymer amount.

• Claim 22 (tear production with concrete excipient set)

  • Is the most composition-explicit: cyclosporin A 0.05%, castor oil 1.25%, polysorbate 80 1.0%, cross-polymer 0.05%, glycerine 2.2%, sodium hydroxide, water.
  • Still requires functional efficacy (increase tear production), but composition is fully enumerated.

Regimen and performance requirements that can constrain design-arounds

• Twice daily is explicit in the independent and method statements provided. A product dosed once daily would reduce direct literal fit for these method claims (subject to doctrine-of-equivalents analysis in litigation, not addressed here).
• pH range 7.2–7.6 is explicitly required for Claim 18 and Claim 23.
• No detectable blood cyclosporin A limits read-through for systemic exposure; it is a functional limitation that can be measured in pharmacokinetic studies.
• Comparator-based dependent claims (13-16) can be used for evidentiary leverage. Literal infringement depends on whether the accused product is “effective” to the claimed degree relative to the specified second emulsion.

Which product and formulation line does the patent track (what is the “second emulsion” comparator inside the claims)?

Answer: The claims reference a comparator emulsion dosed twice daily containing cyclosporin A 0.1% w/w and castor oil 1.25% w/w. That comparator appears as the baseline for effectiveness and safety comparisons, implying the claimed formulation achieves similar or improved outcomes at half the cyclosporin A concentration.

Comparator embeddings

• Claims 13-14: equivalence/superiority in therapeutic effectiveness vs. a second emulsion with 0.1% cyclosporin A.
• Claims 15: faster breakdown in the eye reduces vision distortion vs. a second emulsion containing “only 50% as much castor oil.”
• Claims 16: reduced adverse events vs. a second emulsion with 0.1% cyclosporin A and castor oil 1.25%.

These elements are important for enforcement strategy because they invite “function over formula” proof in addition to formulation composition.

What patents typically surround US 8,648,048 in the U.S. for cyclosporin A ophthalmic emulsions?

Answer: The core U.S. patent landscape for cyclosporin A ophthalmic therapy generally clusters into:

1. Active/compound or core cyclosporin use (dry eye indication and/or ophthalmic administration concepts).
2. Formulation patents for cyclosporin A in microemulsions/emulsions (vehicles, surfactants, polymeric thickeners, oils, pH, tonicity buffers).
3. Method-of-use patents defining dosing regimens and endpoints (tear production, keratoconjunctivitis sicca).
4. Systemic exposure / low absorption claims tied to topical formulations.

However, without the patent’s bibliographic details (assignee, filing date, publication number, and the full citation graph) and without the Orange Book listing tied to a specific NDA/BLA, a complete and accurate “who owns what” map across the entire U.S. estate cannot be produced from the claim text alone.

When does exclusivity end: what does the timing look like for U.S. filing and patent term?

Answer: Claim text alone is insufficient to compute a definitive patent-term expiration or exclusivity end date without the patent’s filing date, priority date, and any terminal disclaimer or PTA.

What Orange Book status would apply to this patent?

Answer: The patent’s Orange Book status depends on which listed drug (NDA) and which patents are listed for that product. The claim text does not identify the NDA number, listed formulation, or the Orange Book patent listing(s). Without that linkage, the Orange Book status cannot be stated accurately.

What Paragraph IV / generic entry risks exist for a cyclosporin A 0.05% ophthalmic emulsion?

Answer: Direct entry risk analysis requires knowing:

• the reference listed drug (RLD) for cyclosporin A at the relevant strength,
• whether the RLD is an emulsion with the same vehicle and pH,
• the patent list for that NDA in the Orange Book, and
• whether US 8,648,048 is listed as a blocking or non-blocking patent.

Those inputs cannot be derived from the claim text provided.

How strong is the patent estate for this specific emulsion: enforceability drivers and attack points

Answer: US 8,648,048’s strength is driven by:

• multi-parameter formulation specificity (exact active concentration plus a defined oil/surfactant/polymer/buffer/pH set),
• explicit dosing (twice daily),
• and measurable functional limits (tear production efficacy, reduced adverse events, “substantially no detectable” cyclosporin A in blood).

Likely infringement/evidence themes

• Formulation matching: accused products must include cyclosporin A at about 0.05% and the specified excipients (polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, castor oil).
• Product microenvironment: pH range 7.2–7.6 and sodium hydroxide buffer can be decisive for the claims that require them.
• PK testing: the “no detectable cyclosporin A” limitation invites systemic exposure testing comparisons.

Likely validity/attack themes that would be asserted in litigation (without speculation of outcomes)

Because the claims are tightly formulated and include functional and comparator-based limitations, a typical validity challenge strategy would target:

• prior art that already disclosed cyclosporin A ophthalmic emulsions with similar excipient systems and pH/tone buffers,
• obviousness under combinations of known ophthalmic vehicles and known cyclosporin A topical regimens,
• and whether “about” ranges and functional equivalence limitations are definite and supported.

Key Takeaways

• US 8,648,048 is a twice-daily topical ophthalmic emulsion method patent for dry eye (keratoconjunctivitis sicca) and increasing tear production using cyclosporin A at ~0.05% w/w.
• Claim scope is composition-specific: the emulsion requires castor oil (~1.25%), polysorbate 80 (~1.0% in tighter claims), and acrylate/C10-30 alkyl acrylate cross-polymer (~0.05%), with glycerine (~2.2%) and sodium hydroxide buffer plus pH 7.2–7.6 in the keratoconjunctivitis sicca/pH-dependent claims.
• Functional limitations matter: claims require efficacy endpoints and include low systemic exposure (“substantially no detectable” cyclosporin A in blood).
• Dependent comparator claims provide enforcement leverage versus a referenced 0.1% cyclosporin A emulsion baseline, including reduced adverse events and vision distortion tied to emulsion breakdown behavior.

FAQs

1. Would a cyclosporin A ophthalmic emulsion dosed once daily avoid literal infringement of US 8,648,048?
2. How do the “substantially no detectable” cyclosporin A in blood limitations affect infringement proof for US 8,648,048?
3. Do the pH 7.2–7.6 limitations in the keratoconjunctivitis sicca claims require sodium hydroxide as the buffer in every case?
4. What excipient changes are most likely to avoid the claim set: substituting the cross-polymer, changing surfactant, or changing oil phase?
5. How do the comparator-based dependent claims (vs. 0.1% cyclosporin A and half castor oil) get used in litigation strategy?

References (APA)

1. United States Patent No. 8,648,048.

Drugs Protected by US Patent 8,648,048

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 8,648,048

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
World Intellectual Property Organization (WIPO)	2005032577