Scope and Claims Review for US Patent 10,406,240 (PSMA Urea Ligand With Hydrophobic Side-Chain Linker and Chelator)
US Patent 10,406,240 is directed to PSMA-targeting urea-based small-molecule radioconjugates (and their salts), with a specific linker architecture and a chelating group configured for radiometal complexation, plus formulations and therapeutic methods for PSMA-expressing disease.
What Is Claimed in 10,406,240?
What is the independent claim scope?
Claim 1 recites a compound defined by the tripartite structure B-L-C (or a salt), where:
- B is a prostate specific membrane antigen (PSMA) ligand that is a urea of two amino acids
- The two amino acids are independently selected from:
- asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, threonine
- and combinations thereof.
- L is a divalent linker of 7 to 20 atoms in length and contains:
- a divalent alkylene group
- a cycloalkylenecarbonyl group
- and a hydrophobic side chain divalent group comprising an arylalkyl side chain
- C is a chelating group that is:
- attached to L at a defined point (*).
- Key structural proviso:
- L has a single hydrophobic side chain divalent group.
In operational terms, the claim is broad across the choice of the two amino-acid urea substituents within the defined list, and it is constrained primarily by the linker content and topology (alkylene + cycloalkylenecarbonyl + arylalkyl hydrophobic side chain, with total 7 to 20 atoms and only one such hydrophobic side-chain unit).
What are the dependent claims adding?
- Claim 2: requires that C is chelated to a radioactive metal isotope.
- Claim 3: fixes connectivity:
- L is covalently bound to C via an amide bond
- L is covalently bound to B via an amide bond
- Claim 4: covers a pharmaceutical composition containing:
- therapeutically effective amount of the compound (or salt)
- plus conventional carriers/diluents/excipients
- Claim 5: covers a method of treating disease involving PSMA-expressing pathogenic cell population by administering:
- therapeutically effective amount of the compound (or salt)
- optionally with carriers/diluents/excipients
Claim Construction: Where the Patent Likely Draws Its Line
How broad is “B” (the PSMA urea ligand)?
Broad within a defined amino-acid universe. Claim 1 allows selection of both urea amino-acid units from a closed set of 10 amino acids. That means infringement can occur even if a competitor uses different allowable amino-acid combinations than the example compounds, as long as the urea remains formed from two chosen members of that list.
Key limiting feature: the “urea of two amino acids” language is not a generic “urea” claim; it specifies the urea is formed from amino acid-derived moieties drawn from the enumerated set.
How constrained is “L” (linker architecture)?
L is the principal claim bottleneck. Claim 1 recites multiple structural elements that must co-exist in a single linker:
- total length: 7 to 20 atoms (not bonds; atoms)
- includes:
- divalent alkylene
- cycloalkylenecarbonyl
- hydrophobic side chain divalent group having an arylalkyl side chain
- proviso: only one hydrophobic side chain divalent group within L
This structure imposes three design constraints on third-party products:
- The linker must contain both an alkylene divalent segment and a cycloalkylenecarbonyl unit.
- The hydrophobic portion must be an arylalkyl side chain, and it must be present as a divalent group (in other words, it participates as part of the chain linking points).
- Competitors must avoid having two hydrophobic side-chain divalent units of the claimed type, because claim 1 explicitly requires a single hydrophobic side chain divalent group.
How broad is “C” (chelating group)?
Claim 1 uses a generic definition: C is a chelating group of the formula, with attachment defined by *, but the provided claim text in the prompt does not disclose the full chelator formula itself.
That means the scope for C can be:
- broad if the chelator formula is an encompassing definition covering multiple chelators in a class, or
- narrower if the formula specifies a single chelator family (or a limited set of alternatives).
Dependent claim 2 further narrows to radiometal-chelated versions.
What does claim 3 add in enforceability terms?
Claim 3 constrains the bonding scheme:
- L to C through an amide bond
- L to B through an amide bond
This matters because competitors could use the same general skeleton (B-L-C) but change the attachment chemistry (e.g., using different linker-attachment bonds such as thioesters, ureas, carbamates, or direct carbon-carbon linkages). Claim 3 would not cover those variants, while claim 1 would still potentially cover them if claim 1 does not require amide bonding. But in many claim sets, the independent claim is drafted to require the linker architecture generally, and the dependent claim specifies the particular covalent bond types that are optionally claimed for added coverage.
Practical Scope Summary by Claim Layer
Claim-by-claim coverage map
| Claim |
Coverage element |
What it adds beyond prior claim |
| 1 |
B-L-C PSMA urea ligand + constrained linker + chelator (salt allowed) |
Baseline composition definition with specific linker features and only one hydrophobic side chain divalent group |
| 2 |
Radiometal form |
Requires chelation of C to a radioactive metal isotope |
| 3 |
Attachment chemistry |
Requires amide bonds between L-C and L-B |
| 4 |
Formulation |
Requires pharmaceutical composition with carriers/diluents/excipients |
| 5 |
Indication/method |
Requires administration to treat PSMA-expressing disease |
Patent Landscape Implications (US Enforcement and Design-Around Points)
Where competitors are most likely to face risk
Risk is highest when a third-party product matches all three of these features:
- PSMA ligand is a urea made from amino acids selected from the enumerated list.
- Linker contains:
- divalent alkylene
- cycloalkylenecarbonyl
- a single hydrophobic side-chain divalent arylalkyl group
- Chelator is attached at the defined linker attachment point (*) consistent with the chelator formula in claim 1.
If an R&D program uses the same or highly similar PSMA-urea motifs and a similar linker architecture (alkylene + cycloalkylenecarbonyl + single arylalkyl hydrophobic side chain), the claim language becomes difficult to avoid.
Likely design-around strategies that would weaken claim 1
Even without knowing the exact chelator formula, the claim provides several explicit escape hatches:
- Linker element substitution
- Remove the cycloalkylenecarbonyl unit or replace it with a different ring carbonyl motif would challenge literal coverage.
- Hydrophobic side-chain count
- Use a linker with zero or more than one hydrophobic side chain divalent group.
- The “single hydrophobic side chain divalent group in L” is a distinct limitation.
- Arylalkyl requirement
- Change hydrophobic substituent so it is not an arylalkyl side chain.
- B ligand amino-acid set
- Use a urea formed from amino acids outside the enumerated list.
- The “selected from” language is a closed list in claim 1.
Design-around strategies that would weaken claims 2 or 3 specifically
- Claim 2: if the product is not a radiometal chelate (e.g., imaging agent without radioactive metal or a non-radioactive analog), claim 2 is avoided.
- Claim 3: avoid amide bonds at both L-C and L-B connections.
Scope of “Treating PSMA-Expressing Disease” (Method Claim)
What does claim 5 cover?
Claim 5 is a standard therapeutic method claim tethered to:
- patient in need of relief,
- disease with pathogenic cell population expressing PSMA,
- administration of a therapeutically effective amount of the claim 1 compound or salt,
- optional carriers/diluents/excipients.
This is not restricted to a tumor type, line of therapy, or route of administration in the text provided. The scope is based on target expression (PSMA) and therapeutic administration.
Commercial and R&D Use: How to Read This for Freedom-to-Operate
What product variants fall within the same claim family?
Under this set of claims, product variants that are likely to be captured include:
- Multiple PSMA-urea ligand permutations using the permitted amino acid list for B.
- Linkers that remain within 7 to 20 atoms and preserve:
- alkylene divalent segment,
- cycloalkylenecarbonyl,
- one hydrophobic arylalkyl divalent side chain.
- Chelator-bearing compounds where C is configured per claim 1’s chelator formula.
- Both therapeutic and radiotherapeutic embodiments via claim 2.
- Formulations and method-of-treatment uses via claims 4 and 5.
What changes most often break coverage?
The most enforceable breaks usually come from:
- changing the linker topology (particularly removal/replacement of cycloalkylenecarbonyl or altering the hydrophobic arylalkyl divalent group constraint),
- using a urea ligand derived from non-listed amino acids for B,
- using attachment chemistry other than amide if claim 3 is asserted,
- changing whether the chelator is actually radiometal-loaded if claim 2 is asserted.
Key Takeaways
- US 10,406,240 is anchored on B-L-C PSMA-targeted urea ligands with a specific 7 to 20 atom linker architecture containing alkylene + cycloalkylenecarbonyl + exactly one hydrophobic arylalkyl divalent side chain.
- The independent claim (1) is broad on which amino acids form the urea, limited by a closed list.
- The independent claim is narrow on linker composition and topology, making L the primary infringement and design-around battleground.
- Dependent claims add enforceable incremental coverage for radiometal chelation (2), amide connectivity (3), and standard formulation (4) and PSMA-expressing disease treatment (5).
FAQs
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Does claim 1 require the compound to be radiolabeled?
No. Claim 1 covers the compound structure (B-L-C). Claim 2 specifically requires chelation to a radioactive metal isotope.
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What limits the linker in claim 1?
Claim 1 requires 7 to 20 atoms and includes a divalent alkylene group, a cycloalkylenecarbonyl group, and a single hydrophobic arylalkyl divalent side chain within L.
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Can different amino acid pairs still infringe under claim 1?
Yes, if both urea amino acids are independently selected from the enumerated list (asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, threonine).
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What does claim 3 add beyond claim 1?
Claim 3 requires specific covalent attachment chemistry: amide bond between L and C, and amide bond between L and B.
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Is the method claim limited to a specific cancer type?
Based on the provided text, claim 5 is limited by PSMA expression on pathogenic cells, not by a named cancer type.
References
[1] US Patent 10,406,240. “A compound of the formula B-L-C…” (claims 1-5 as provided in user prompt).
