United States Patent 7,332,472 (Cyclosporine 1-Amino Acid 1,3-Diene Isomeric Mixtures) Claim Scope and US Patent Landscape
Executive summary: US Patent 7,332,472 covers an isomeric cyclosporine analogue mixture defined by (i) a 1-amino acid residue modification incorporating a 1,3-diene substituent and (ii) E/Z composition ranges heavily skewed to the E-isomer (independent composition claims at ~90–95% E and ~10–5% Z, and a second range at ≥95% E and ≤5% Z). Dependent claims broaden coverage into pharmaceutical compositions (oral dosage forms including gelatin capsules and specific liquid vehicles with surfactant, ethanol, and lipophilic/amphiphilic solvents including vitamin E TPGS plus MCT and Tween 40), dosing windows (including 50 mg/mL strength), and method claims for immunosuppression across transplant rejection and a wide autoimmune/inflammatory disease set. Downstream value is concentrated in: (a) isomeric composition parameters that constrain design-around; (b) oral formulation vehicles that can be targeted in generic development; and (c) wide therapeutic method claims that increase exposure for label use and off-label compounding. The patent likely sits within the broader cyclosporine-analogue and isomer-purified or isomer-optimized space where multiple patents can coexist on the drug substance, the formulation, and the therapeutic use.
What is US Patent 7,332,472 and what does it claim?
Core invention in one line: A cyclosporine analogue isomeric mixture created by modifying the cyclosporine 1-amino acid residue with a 1,3-diene substituent, where the mixture is defined by E/Z isomer ratios and is used to provide immunosuppression with reduced toxicity and/or increased efficacy versus cyclosporine A.
Independent claim structure (what is legally “must-have”)
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Composition claim (isomeric mixture defined by E/Z ratio)
- Claim 1: E-isomer about 90% to about 95%, Z-isomer about 10% to about 5%.
- Claim 2: E-isomer ≥ about 95%, Z-isomer ≤ about 5%.
- Both are cyclosporine analogues with:
- 1-amino acid residue modification
- 1,3-diene substituent
- Mixture is specifically the E and Z isomers “as specified below” (the dependent statement indicates the patent includes definitional chemistry elsewhere in the specification, which is not reproduced in the prompt).
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Pharmaceutical composition claim
- Claim 3 ties the above mixture to a pharmaceutically acceptable excipient.
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Method-of-use claims
- Claim 17: “administering” a therapeutically effective amount to an animal.
- Claim 24: acute transplant rejection.
- Claim 26-30: T-cell mediated rejection, graft-versus-host disease, chronic rejection.
- Claim 34-37: broad autoimmune/inflammatory disease categories.
- Claim 40-43: utility framing around reduced toxicity vs cyclosporine A and increased efficacy vs cyclosporine A, defined through “preparing an isomeric mixture of claim 1 or 2.”
What the E/Z ratio does to claim scope (design-around leverage)
The E/Z constraints are not cosmetic; they are the identity boundary. Any accused product must fall within the claimed E content and Z content ranges for the mixture.
- If a competitor shifts to a different E/Z distribution (below ~90% E or above ~5% Z for the tighter range), literal infringement becomes harder.
- If a competitor narrows the distribution to essentially pure E isomer (for example, >98% E and <2% Z), infringement is not automatically avoided because the claim 2 range still includes E ≥95% and Z ≤5%. A “near-pure E” product can still read on claim 2.
- If a competitor deliberately targets a different isomer ratio (for example, E ~88% with Z ~12%), claim 1 may be avoided but claim 2 is also avoided.
What must be true about the substituent identity
Both claim 1 and 2 require a cyclosporine analogue modified at the 1-amino acid residue with a 1,3-diene substituent. If the competitor uses a different linker, different diene geometry, different placement on the molecule, or a different substituent class, claim 1/2 become vulnerable even if the E/Z ratio matches.
How broad is the formulation coverage in US 7,332,472?
Featured snippet answer: The patent covers oral pharmaceutical compositions including gelatin capsules and specific liquid solutions using surfactant plus ethanol with lipophilic/amphiphilic solvents; dependent claims recite an example vehicle: vitamin E TPGS + MCT oil + Tween 40 + ethanol, at strengths up to 50 mg/mL and oral unit doses ~5 to 500 mg.
Key formulation claim components
- Oral dosage form: Claim 11: formulated for oral administration.
- Capsule form: Claim 4: gelatin capsule containing the isomeric mixture.
- Liquid oral solution vehicle: Claims 6-7:
- surfactant + ethanol + lipophilic and/or amphiphilic solvent
- example solvent system: d-alpha Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), MCT oil, Tween 40, ethanol
- Strength and dosing units:
- Claim 5: about 50 mg isomeric mixture (unit dosage exemplar)
- Claim 9: about 5 mg to about 500 mg per unit
- Claim 10: liquid solution at 50 mg/mL
- Unit dosage form: Claim 8 ties claim 7 to “unit dosage form”
- Dosage regimen framing: Claim 12-16 define dose per kilogram/day and twice-daily scheduling.
Design-around implications (vehicle substitution vs mixture infringement)
- If an accused generic uses a different excipient system than the example recited in claim 7, infringement depends on whether the independent claim 3 (composition with pharmaceutically acceptable excipient) and the other formulation dependent claims are implicated. Claim 3 is wide; claim 7 is narrow.
- The safest generic strategy is usually:
- stay outside the mixture identity (E/Z and substituent constraints), and/or
- stay outside the claimed strength/dosage form if those are the only remaining hooks.
- Here, because claim 3 and claim 11 are broad (pharmaceutical composition for oral administration), formulation changes alone may not eliminate exposure.
What dosing ranges and administration timing are covered?
Featured snippet answer: The patent covers oral dosing roughly 0.05–50 mg/kg/day across claim 12-16 with narrower windows including 2–6 mg/kg/day administered twice daily, and also narrower 0.5–3 mg/kg/day twice daily.
Dose per kg/day (numerical claim ladder)
- Claim 12: 0.05 to 50 mg/kg/day
- Claim 13: 0.1 to 10 mg/kg/day
- Claim 14: 0.5 to 10 mg/kg/day
- Claim 15: 2 to 6 mg/kg/day, twice daily
- Claim 16: 0.5 to 3 mg/kg/day, twice daily
Strength example linkage
- Claim 10: 50 mg/mL
- Claim 5/9: “about 50 mg” unit and “5–500 mg” unit dose exemplars
- Claim 15/16 specify administration orally twice daily, consistent with formulation designed for split dosing.
Method claim alignment (substance + regimen)
Claims 17-23 mirror the composition’s dosing language in a method-of-use context:
- Claim 17-19: general “administering immunosuppression” and human animal.
- Claim 22-23: twice-daily dosing aligned to 2–6 mg/kg/day and 0.5–3 mg/kg/day ranges.
This alignment matters for litigation because even if the formulation is changed, label-directed dosing could still land inside the method claims.
Which therapeutic areas are covered by the method claims?
Featured snippet answer: The patent covers immunosuppression for acute and chronic transplant rejection, T-cell mediated rejection, graft-versus-host disease, xenograft rejection (including antibody- and B-cell mediated rejection), and broad autoimmune/inflammatory conditions including rheumatoid arthritis, lupus, inflammatory bowel disease, psoriasis, and many dermatologic and pulmonary/allergic conditions.
Transplant and immune rejection scope
- Acute organ/tissue transplant rejection (claim 24)
- heart, lung, combined heart-lung, liver, kidney, pancreatic, skin, bowel, corneal (claim 25)
- T-cell mediated rejection (claim 26)
- Graft-versus-host disease after bone marrow transplantation (claims 27-28)
- Chronic rejection (claim 29), specifically graft vessel disease (claim 30)
- Xenograft rejection (claim 31-33)
- acute/hyperacute/chronic (claim 32)
- rejection mediated by B-cells or antibody-mediated rejection (claim 33)
- Prevent allograft or xenograft rejection (claim 38-39)
- rejection of kidney, heart, liver
Autoimmune and inflammatory disease coverage (breadth)
Claims 34-37 list extensive disease clusters, including:
- arthritis/rheumatic diseases (claim 35)
- hematological disorders and systemic autoimmune conditions (claim 36)
- detailed skin/allergy/airway conditions (claim 37), including asthma, contact dermatitis, atopic dermatitis, urticaria, bullous pemphigoid, lupus erythematosus, pemphigus, and multiple others.
Practical litigation exposure
A broad method-claim set can create:
- higher settlement leverage in generics and biosimilars if any label or promotional materials map into covered indications, and
- higher risk for compounding/expanded use if the product is marketed or used for covered conditions with the claimed dosage regimen.
What utility assertions appear, and how do they affect enforceability?
Featured snippet answer: The patent includes two “preparing the mixture for use” utility method claims tied to comparative outcomes versus cyclosporine A: reduced toxicity (claim 40-41) and increased efficacy (claim 42-43).
“Preparing for use” comparative utility claims
- Claim 40: method of reducing toxicity by preparing the isomeric mixture for use as an immunosuppressive agent, with reduced toxicity relative to cyclosporine A.
- Claim 42: method of increasing efficacy by preparing the isomeric mixture for use as an immunosuppressive agent, with increased efficacy relative to cyclosporine A.
- Claims 41 and 43 repeat dosage amounts within specific ranges (0.05–50 mg/kg/day down to 0.5–3 mg/kg/day twice daily) for the comparative utility frame.
In infringement practice, these comparative utility hooks often intersect with evidence of superiority and may be used to support the patent’s claimed therapeutic advantage, depending on claim construction and evidentiary record in the file history and specification.
When does US 7,332,472 expire and when could generics enter?
No expiration date, patent grant/filing dates, terminal disclaimer status, PTA, or prosecution history are provided in the prompt. Without those, a correct exclusivity timeline cannot be computed.
What does the US patent landscape likely look like around this cyclosporine analogue?
Executive summary of landscape shape: US Patent 7,332,472 is one layer in a typical cyclosporine-analogue stack. Enforcement usually comes from a combination of:
- drug substance patents that define chemical identity and isomer composition,
- formulation patents tied to oral delivery vehicle and strength,
- method-of-use patents for transplant and immunological indications, and
- sometimes manufacturing/process patents for producing the isomeric mixture and controlling E/Z ratios.
Because the prompt includes only the claim text of US 7,332,472, only claim-scope conclusions can be made, not the full list of co-pending or related US patents.
How many other US patents would typically cover the same cyclosporine analogue space?
Answer: Not computable from the information provided. The request is to “analysis of the scope and claims and patent landscape,” but no bibliographic data (assignee, application number, related family members, prosecution links, or citing/ancestor patents) is included.
What are the key infringement “hot spots” for US 7,332,472?
Hot spot 1: substance identity via E/Z composition ranges
Literal infringement requires:
- cyclosporine analogue
- 1-amino acid residue modification with a 1,3-diene substituent
- mixture composition within the claimed E/Z ratios (claims 1-2)
High-risk scenario: an authorized or infringing product whose analytical specs show E ≥90% and Z ≤10% (claim 1) or E ≥95% and Z ≤5% (claim 2).
Hot spot 2: oral formulation framing
Claim 3 plus claim 11 is broad (pharmaceutical composition with pharmaceutically acceptable excipient for oral administration). Claims 4, 6-10 narrow into gelatin capsule and a specific liquid vehicle example.
High-risk scenario: any generic marketing oral cyclosporine analogue product using the claimed mixture with standard oral excipient sets, especially if the vehicle matches the example system.
Hot spot 3: dosing regimens and twice-daily administration
Claims 15-16 and the mirrored method claims 22-23 specify:
- 2–6 mg/kg/day twice daily
- 0.5–3 mg/kg/day twice daily
High-risk scenario: label-directed or studied dosing within those windows for covered indications.
Hot spot 4: indication/clinical use
Claims cover:
- acute and chronic transplant rejection,
- T-cell mediated rejection,
- GVHD,
- xenograft rejection including antibody- and B-cell mediated,
- wide autoimmune/inflammatory indications.
High-risk scenario: promotional use, investigator-initiated trial outcomes, or label expansions aligning with those indications and dosing.
Key Takeaways
- US 7,332,472’s center of gravity is an isomeric cyclosporine analogue mixture defined by a 1-amino acid residue 1,3-diene modification and tight E/Z composition parameters (claim 1 ~90–95% E; claim 2 ≥95% E).
- The patent’s enforceability vectors include both substance composition and method-of-use across transplant and autoimmune/inflammatory indications, with oral formulation coverage and specific example vehicles (vitamin E TPGS + MCT + Tween 40 + ethanol) at exemplified strengths (including 50 mg/mL).
- The largest litigation and licensing risk for competitors is any product whose analytical isomer profile falls within the claimed E/Z ranges and whose clinical use and dosing regimen align with the method claims.
- A full US patent landscape (related patents, expiration dates, Orange Book listings, Paragraph IV posture, and litigation outcomes) cannot be generated from the prompt alone because no patent-family or regulatory-bibliographic data is included.
FAQs
- Does US 7,332,472 cover essentially pure E-isomer cyclosporine analogue mixtures?
- Can a competitor avoid infringement by changing the oral excipient system while keeping the same isomeric mixture?
- Which specific claims are most likely to be asserted in litigation: composition claims or method-of-use claims?
- Do the disease lists in claims 34-37 function as independent infringement hooks or as context for method claims tied to dose and administration?
- How should analytical testing of E/Z ratios be structured to assess design-around risk under claims 1 and 2?
References (APA)
- United States Patent 7,332,472.
