Scope and claims of US 7,737,112 and the U.S. patent landscape around cyclodextrin-formulated “peptide epoxy ketone proteasome inhibitors”
US 7,737,112 claims a formulation platform that uses a substituted beta-cyclodextrin, specifically hydroxypropyl beta-cyclodextrin (HPβCD) or sulfobutyl ether beta-cyclodextrin (SBECD), to make a practically insoluble peptide epoxy ketone proteasome inhibitor usable in aqueous solution or as a water-soluble solid/lyophilisate, with explicit minimum in-water concentration requirements and optional buffer pH ionization ranges. The independent claim is directed to the combination of (i) the specific inhibitor class and (ii) the specified cyclodextrin substituents; the dependent claims carve out dosage form and performance thresholds (solution vs. lyophilisate/solid; dissolved concentration minima; buffer-induced ionization) and then broaden the “inhibitor” definition by including multiple structural formula sets (II through XVI and others) and label-containing derivatives.
The claim coverage is formulation-focused rather than molecule-synthesis focused: it does not claim a method-of-treatment, dosing regimen, or clinical use. Instead, it targets what a generic or biosimilar-adjacent entrant would likely have to reproduce to sell an injectable aqueous product without precipitation.
What does US 7,737,112 claim: a cyclodextrin complex system for insoluble peptide epoxy ketone proteasome inhibitors?
Short answer (claim scope): US 7,737,112 is a U.S. formulation composition patent. The claim “center of mass” is the composition of a practically insoluble peptide epoxy ketone proteasome inhibitor (or salt) with substituted beta-cyclodextrins selected from HPβCD and SBECD, in liquid aqueous solution or solid dosage forms that dissolve in water at specified concentrations. (Claims 1–8, 10, 14–16, 29–32)
Independent claim 1: the combination that defines infringement
Claim 1 requires all of:
- A pharmaceutical composition comprising:
- “a practically insoluble peptide epoxy ketone proteasome inhibitor” (or salt)
- and a substituted cyclodextrin selected from HPβCD and SBECD
- The inhibitor must fall within what the specification defines as those “structural formula” ranges (Claims 15–28 list multiple structural formula embodiments that function as supported “inhibitor” examples/broad definitions inside the claim family).
Practical coverage implication: A product that substitutes a different solubilizer (eg, polysorbate, PEG, propylene glycol) without using HPβCD or SBECD is outside claim 1. A product that uses SBECD/HPβCD with a non-matching inhibitor identity or outside the supported structural formula definition is also outside.
Independent claim 29: an additional broad formulation anchor
Claim 29 adds broader “compound having a structure or a pharmaceutically acceptable salt thereof” with the same cyclodextrin selection (HPβCD or SBECD). That typically reduces disputes about whether a competitor’s inhibitor is “the peptide epoxy ketone proteasome inhibitor” as characterized in Claim 1, because Claim 29 is structured as a “compound having a structure” formulation plus cyclodextrin.
Specific embodiments: claims 31–32 lock down “how it’s made into a product”
- Claim 31: aqueous solution containing 10% (w/v) SBECD and 10 mM citric acid adjusted to pH 3.5
- Claim 32: lyophilisate comprising SBECD and the inhibitor compound
These are the most “design-around sensitive” claim hooks: if a generic changes concentration, acid type, pH, or avoids lyophilization, it may avoid the narrow dependent-claim embodiments while still risking broader Claim 1/29 coverage if the core inhibitor + SBECD combination is reproduced.
What peptide epoxy ketone proteasome inhibitor structures are covered: structural formula sets II to XVI and label/probe derivatives?
The dependent claims list multiple structural formula embodiments. While the patent text you provided does not include the chemical structures themselves, it does specify that the inhibitor may be represented by many structural formula blocks.
Claim 15–18: inhibitor represented by structural formula (II), (III), (IV), (V)
- Claim 15: structural formula (II) or salt, with X = oxygen and R1–R5 definition language.
- Claim 16: structural formula (III) or salt.
- Claim 17: structural formula (IV) or salt with “at least one of R1–R4 is a group of formula (IIIa).”
- Claim 18: structural formula (V) or salt with extensive variable definitions, including rules like “when R6 is H, L is C═O, and Q is absent, R7 is not hydrogen…”
Claim 19–22: structural formula (VI) and (VII), then (VIII)
- Claim 19: structural formula (VI)
- Claim 20: structural formula shown in the dependent claim (text cut in your excerpt at “following structural formula”)
- Claim 21: structural formula (VII) with additional constraints about forbidden bonds (no O—O, N—O, S—N, S—O bonds)
- Claim 22: structural formula (VIII) and the same forbidden-bond constraint concept
Claim 23–28: structural formula (IX), (X), (XI), then (XII)/(XIV), and (XV)/(XVI)
- Claim 23: structural formula (IX)
- Claim 24: structural formula (X)
- Claim 25: structural formula (XI) including “R7 comprises a detectable label”
- Claim 26: structural formula (XII) with detectable label in R7
- Claim 27–28: structural formula (XII) or (XIV) with Ar/Y/L/Z/R groups and ring-forming rules; Claim 27 then tightens via formula (XV)/(XVI) in Claim 28
Coverage implication (important for landscape and generic risk):
- The claim set explicitly reaches labeled derivatives (Claims 25–26). That increases risk for competitors seeking to market imaging/diagnostic conjugates as formulations of the same inhibitor scaffold with a label.
- The extensive “variable” definitions and multiple formula blocks show the patent is trying to keep the inhibitor definition broad across a family of peptide epoxy ketone proteasome inhibitors, not a single named molecule.
When does the cyclodextrin formulation become infringement territory: aqueous solubility thresholds, solution vs. solid, and buffer pH ionization limits?
Solution form performance requirements (Claims 2–5)
- Claim 2: composition is a solution
- Claim 3: solution comprises at least 0.02 mg/mL inhibitor
- Claim 4: at least 0.1 mg/mL
- Claim 5: at least 1 mg/mL
These are quantitative product-performance claim dependencies. A competitor could attempt to formulate at lower achieved aqueous concentrations to argue non-infringement of those dependent claims, but that does not eliminate risk under Claim 1/29, which may still be infringed if the formulation uses HPβCD or SBECD with the covered inhibitor (the dependent concentration thresholds only matter for those narrower limitations).
Water-soluble solid dissolution thresholds (Claims 6–9)
- Claim 6: composition is a water-soluble solid
- Claim 7: dissolves in water at least 0.02 mg/mL
- Claim 8: dissolves at least 0.1 mg/mL
- Claim 9: dissolves at least 1 mg/mL
Again, these are dependent claim carveouts aimed at solid dosage forms that reconstitute in water.
Buffer pH ionization constraints (Claims 10–13)
- Claim 10: further comprising a buffer
- Claim 11: buffer is a salt
- Claim 12: buffer achieves pH where at least 10% of inhibitor molecules are ionized
- Claim 13: pH where at least 50% are ionized
This matters for design-around strategies:
- A competitor could choose a different buffer system and pH profile that does not reach those ionization percentages, potentially avoiding Claims 12–13 while still using SBECD/HPβCD. However, if the core “inhibitor + cyclodextrin” combination is present, they may still be exposed under Claim 1/29.
Explicit narrow formulation: SBECD + citric acid at pH 3.5 (Claim 31)
- Claim 31 is a concrete target: 10% (w/v) SBECD and 10 mM citric acid adjusted to pH 3.5.
A generic formulation that uses SBECD but changes:
- SBECD concentration,
- acid identity (instead of citric acid),
- or pH
may avoid Claim 31 specifically. It still remains vulnerable under broader Claim 1/29 if the general formulation still matches.
Lyophilisate form (Claim 32)
- Claim 32: lyophilisate comprising SBECD and the inhibitor compound.
If a competitor uses a different solidification strategy that does not produce a “lyophilisate” (and avoids SBECD in the final composition), it may reduce risk, but most process alternatives still risk Claim 1/29 if the final marketed formulation includes SBECD with the covered inhibitor.
What patent landscape issues matter in the U.S.: composition claim strategy, design-around levers, and likely litigation fault lines
Because the claim is formulation-centric, the landscape analysis in the U.S. typically turns on three questions: (1) whether the “inhibitor” is within the structural formula set, (2) whether the solubilizer is HPβCD or SBECD, and (3) whether the product achieves the dependent quantitative performance and buffer/lyophilisate limitations.
Likely “hot” infringement elements
- Cyclodextrin identity and substitution: only HPβCD and SBECD are named in Claim 1.
- “Practically insoluble” characterization: this is a factual/technical dispute magnet. But Claim 1 reads on “practically insoluble peptide epoxy ketone proteasome inhibitor,” and the dependent structural formula list suggests the patent’s specification ties “practically insoluble” to that scaffold family.
- Formulation achieved concentration and dissolution thresholds: Claim 3–5 and 7–9 create numeric infringement pressure points.
- pH/ionization reached with a buffer salt: Claim 12–13 create additional measurable conditions.
- Lyophilisate status and SBECD presence: Claim 32 is binary in practice.
Design-around levers a generic typically tries
- Replace cyclodextrin with a different excipient system (avoid HPβCD and SBECD entirely) to exit Claim 1.
- Keep cyclodextrin but remove/alter the measurable thresholds (concentration/dissolution limits) to exit dependent claims. This does not fully eliminate risk against Claim 1/29.
- Keep SBECD but change acid system and pH to miss Claim 31.
- Avoid lyophilisate form to miss Claim 32 (still potentially exposed under Claim 1/29).
Litigation fault lines typical for this patent type
- Scope of “inhibitor” definitions: validity and infringement often hinge on whether the accused inhibitor truly falls within the claimed structural formula scope.
- Product testing evidence: concentration, dissolution rate/concentration, pH and ionization fraction are measurable, so expert testing and batch-to-batch variability can become decisive.
- Solubilizer substitution: disputes often reduce to whether a competitor’s product uses HPβCD/SBECD “as defined” or uses a closely related material not literally covered.
How strong is US 7,737,112 likely to be: what the claim structure signals about enforceability
On the face of the claim set you provided, the patent shows:
- Clear, narrow excipient selection (HPβCD or SBECD) which can help infringement clarity.
- Multiple dependent quantitative limits (mg/mL minima; dissolution concentration minima).
- Explicit formulation examples (10% SBECD, 10 mM citric acid, pH 3.5; lyophilisate).
Those features tend to strengthen enforceability against close formulation copies. Weaknesses, where they arise, usually come from:
- Over-breadth of the inhibitor “structural formula” coverage (if competitors argue their inhibitor scaffold is outside those defined structures).
- Potential prior art that combines known proteasome inhibitors with known cyclodextrin solubilization strategies. Without file history, prosecution record, and citation list, the strength cannot be reliably scored here.
What formulations are protected by US 7,737,112: solution, water-soluble solid, and lyophilisate with SBECD/HPβCD
Protected product types
- Aqueous solution containing inhibitor + HPβCD/SBECD (Claims 2–5)
- Water-soluble solid that dissolves in water to at least the claimed mg/mL levels (Claims 6–9)
- Buffered aqueous preparations with salts achieving ionization thresholds (Claims 10–13)
- SBECD/citric acid at pH 3.5 at 10% w/v SBECD (Claim 31)
- Lyophilisate containing SBECD and the inhibitor (Claim 32)
Protected inhibitor class within those dosage forms
The inhibitor can be any compound falling under the structural formula definitions (II through XVI as stated in Claims 15–28) including detectable-label variants (Claims 25–26).
Orange Book status, exclusivity, and litigation/Paragraph IV risks for US 7,737,112
No U.S. regulatory listing, Orange Book entry, listed patents, expiration date, or active Paragraph IV litigation/settlement is provided in your prompt. Without that record-level data, this cannot be mapped to specific FDA approvals, NDCs, or generic launch dates.
Key takeaways
- US 7,737,112 is a formulation composition patent focused on making a practically insoluble peptide epoxy ketone proteasome inhibitor workable in water using HPβCD or SBECD.
- Independent claims 1 and 29 cover broad “inhibitor + substituted beta-cyclodextrin” compositions in pharmaceutical form.
- Dependent claims add measurable thresholds: solution concentration minima (0.02, 0.1, 1 mg/mL), dissolution minima for water-soluble solids (same scale), and buffer salt pH requirements that yield defined ionization fractions (≥10% and ≥50%).
- Narrow embodiments constrain exact product recipes: 10% (w/v) SBECD + 10 mM citric acid at pH 3.5 (Claim 31) and SBECD-containing lyophilisates (Claim 32).
- The patent reaches multiple inhibitor structural formula embodiments (II–XVI blocks) including detectable-label versions, which expands competitive risk beyond just the base therapeutic molecule.
FAQs
- Can a competitor avoid US 7,737,112 by using a different solubilizer like polysorbate or PEG instead of SBECD/HPβCD?
- If a generic uses SBECD but formulates below 0.02 mg/mL in water, does it avoid the dependent claims?
- Does the lyophilisate limitation (Claim 32) require freeze-drying equipment, or is the final dosage form label sufficient?
- How do “buffer achieving X% ionized” limits translate into lab tests during infringement analysis?
- Do detectable-label structural formula claims (Claims 25–26) create additional exposure for imaging conjugates built on the same proteasome inhibitor scaffold?
References
No external sources were used because the prompt provided only claim text and did not include bibliographic patent metadata, file history, prosecution citations, FDA/Orange Book listings, or litigation records.
