United States Patent 11,311,604 (US11311604): Scope, Claims Architecture, and Patent Landscape for Controlled-Release CNP Agonists
US 11,311,604 is directed to a controlled-release CNP (C-type natriuretic peptide) agonist system that releases CNP in free form with defined pharmacological potency and extended release kinetics, built around (i) a reversible prodrug linker architecture (L1), (ii) a second modular element (L2), and (iii) a branched water-soluble polymer or hydrogel segment (Z / Z′) that is positioned to control release and tissue exposure. The claims then cascade into (a) a pharmaceutical composition claim and (b) broad therapeutic method-of-use coverage tied to a long list of diseases and, in dependent claims, specific conditions including achondroplasia and select craniosynostosis/apert-family syndromes.
What does claim 1 actually cover?
Is the invention a new CNP peptide, a prodrug, or a conjugate platform?
Claim 1 is a platform claim for “controlled-release CNP agonist” conjugates/prodrugs rather than a single peptide sequence alone. The claim anchors on a conjugate where the “CNP agonist moiety” (D) is defined by multiple allowed CNP sequences (SEQ ID NO:1 through SEQ ID NO:95). The potency and release performance are then defined by how that moiety is presented and released.
Key structural and functional elements in claim 1:
-
Controlled-release pharmacology
- Releases a CNP agonist in free form.
- Release half-life is constrained in dependent claims:
- Claim 1 sets the baseline: ≥ 6 hours under physiological conditions.
- Dependent claims expand: ≥ 24 hours (claim 8) and ≥ 168 hours (claim 9).
-
Potency selection by NPR-C receptor “IC50 shift”
- Controlled-release CNP agonist: IC50 to NPR-C is at least 5-fold higher than the IC50 of the corresponding free CNP agonist (claim 1).
- Dependent claim escalations:
- ≥ 20-fold (claim 6)
- ≥ 50-fold (claim 7)
-
Allowed molecular scaffolds
- The controlled-release conjugate is of formula (Ia) or (Ib):
- ZL2-L1-D)x (Ia)
- DL1-L2-Z)y (Ib)
- Or it “comprises a conjugate D-L” with the same conceptual components, i.e., D attached through a reversible linker to L elements and then to Z/Z′.
-
Reversible prodrug linker (L1)
- “-L1- is a reversible prodrug linker moiety which is covalently and reversibly conjugated” to:
- the side chain of an amino acid residue on the ring moiety of D, or
- the backbone of the ring moiety of D.
-
Modularity via L2
- L2 is either:
- a chemical bond, or
- a spacer moiety.
-
Polymer/hydrogel control element (Z / Z′)
- Z: “a water-soluble branched polymer moiety” with a branching point constraint:
- “first branching point less than 50 atoms from the CNP moiety.”
- Z′: “a hydrogel.”
-
Stoichiometry/modulation variables
- x: integer 1 to 16
- y: integer 1 to 5
-
Repertoire of peptide sequences
- “CNP moiety having a sequence selected from SEQ ID NO:1 … SEQ ID NO:95.”
How broad is the claim in practice?
Broadness is driven by three “axes” that are each wide:
- D (CNP agonist sequences): 95 permitted sequences.
- Polymer presentation: branched water-soluble polymers with hydrogel elements and variable attachment architecture (Ia vs Ib; x vs y).
- Performance windows: release half-life and NPR-C IC50 shift create functional limitations without locking to a single chemical species.
What narrows enforceability is that claim 1 requires:
- free-form CNP release (not just NPR-C receptor avoidance),
- a quantitative potency shift relative to free CNP (IC50 ratio),
- and a specific reversible prodrug linker positioning (side chain vs backbone) within D.
Claims 2–10: how scope expands into composition and use
What do claims 2–3 cover?
- Claim 2: A pharmaceutical composition comprising:
- the controlled-release CNP agonist of claim 1 plus at least one excipient.
- Claim 3: A method for treating/controlling/delaying/preventing disease in a mammalian patient by administering:
- the controlled-release CNP agonist of claim 1 or
- the pharmaceutical composition of claim 2.
This is a standard composition and method wrapper around the central platform.
How broad is claim 4’s disease list?
- Claim 4 lists diseases that can be treated with a CNP agonist. The list is extensive and spans:
- multiple skeletal dysplasias (achondroplasia/hypochondroplasia type categories, osteochondrodysplasias),
- craniofacial/syndromic growth and bone disorders,
- congenital short stature indications,
- osteoarthritis,
- endocrine-growth related categories (including SHOX deficiency, growth hormone deficiency),
- and several genetic/syndromic conditions such as Marfan syndrome, McCune-Albright syndrome, and neurofibromatosis/LEOPARD/Noonan spectrum disorders.
This is a high-coverage use claim. It does not require a single mechanism beyond “diseases which can be treated with a CNP agonist,” but it anchors the disease universe with the enumerated list.
Where do the dependent claims tighten the target?
- Claim 5: disease is achondroplasia.
- Claim 10: disease selected from:
- Muenke syndrome, Crouzon syndrome, Apert syndrome, Jackson-Weiss syndrome, Pfeiffer syndrome, and Crouzondermoskeletal syndrome.
Together, claims 4/5/10 support two commercial vectors:
- skeletal dysplasia market (notably achondroplasia),
- craniosynostosis/syndromic craniofacial markets.
Functional claim constraints that drive non-infringement strategies
Does the claim require a specific PK profile?
Yes. Claim 1 requires:
- release half-life ≥ 6 hours under physiological conditions.
Dependent claims require longer durations:
- ≥ 24 hours (claim 8)
- ≥ 168 hours (claim 9)
For design-arounds, this means an accused product would need to have a release profile that does not meet those release half-life thresholds in the relevant “physiological conditions” test context, and also still release CNP in free form. If the product releases CNP in bound form or via alternate mechanisms, it can also break the “free form” requirement.
How is NPR-C selectivity built into infringement risk?
The claim’s “IC50 to NPR-C receptor at least 5-fold higher than free CNP agonist” is a quantitative threshold. Dependent claims raise the bar further.
A non-infringing approach must address both:
- release half-life, and
- NPR-C IC50 ratio.
If a competitor’s conjugate releases free CNP but does not materially raise the NPR-C IC50, it likely misses the claim. If it raises NPR-C IC50 but releases CNP too fast (or not in free form), it also misses.
Does the claim lock the linker reversibility?
The claim requires a “reversible prodrug linker moiety” and covalent and reversible conjugation to D at a specified location (side chain or backbone). A design-around would need a different functional linkage type that is not “reversible prodrug linker” in the claim’s sense, or places the linkage in a way not covered by the permitted conjugation positions.
Claim mapping (high-level) to likely product archetypes
What types of products fit claim 1’s architecture?
Claim 1 best matches:
- CNP agonists tethered to branched hydrophilic polymer carriers via reversible prodrug linkers,
- where the polymer/hydrogel domain modulates release kinetics and/or proteolysis/hydrolysis,
- with the CNP moiety temporarily masked such that the NPR-C receptor encounters a lower functional binding profile until release.
What types of products are likely out of scope?
- Conjugates that do not release free CNP.
- Conjugates that release free CNP but do not meet NPR-C IC50 shift thresholds.
- Long-acting formulations that rely on depot mechanisms without matching the reversible linker + Z/Z′ polymer architecture.
Scope summary by claim layer
| Claim |
Scope type |
Core limitations that define coverage |
| 1 |
Product/platform |
Controlled-release CNP agonist with free-form release; release half-life ≥ 6 hours; NPR-C IC50 at least 5-fold higher vs free CNP; structure of (Ia)/(Ib) with D as one of SEQ ID NO:1–95; D linked via reversible prodrug linker L1 and modular L2; Z branched water-soluble polymer with first branching point <50 atoms; Z′ hydrogel; x=1–16 and y=1–5 |
| 2 |
Composition wrapper |
Claim 1 agent + excipient |
| 3 |
Method wrapper |
Administer therapeutically effective amount for any disease treatable with CNP agonist (as enumerated in dependent claims) |
| 4 |
Use expansion |
Disease list includes skeletal dysplasias, craniofacial syndromes, growth disorders, osteoarthritis, genetic syndromes, and related indications |
| 5 |
Use tightening |
Achondroplasia |
| 6 |
Potency tightening |
NPR-C IC50 at least 20-fold higher vs free CNP |
| 7 |
Potency tightening |
NPR-C IC50 at least 50-fold higher vs free CNP |
| 8 |
PK tightening |
Release half-life ≥ 24 hours |
| 9 |
PK tightening |
Release half-life ≥ 168 hours |
| 10 |
Use tightening |
Craniosynostosis/apert family syndromes: Muenke, Crouzon, Apert, Jackson-Weiss, Pfeiffer, Crouzondermoskeletal |
Patent landscape: what this patent implies about competitive space
Where is the “center of gravity” for freedom-to-operate (FTO)?
The practical FTO center for US 11,311,604 is the intersection of:
- CNP moiety masking/unmasking through a reversible prodrug linker (L1),
- polymer/hydrogel-bearing release control (Z and Z′),
- and quantitative performance (release half-life and NPR-C IC50 shift).
Competitors can avoid infringement only by missing one of these three pillars.
How the breadth creates risk for adjacent chemistries
Because claim 1 allows:
- broad selections for D (95 sequences),
- broad x (1–16) and y (1–5),
- structural permutations between (Ia) and (Ib) and through conjugate D-L language,
the claim can reach multiple chemistry variants as long as the performance criteria and reversible linker/polymer architecture are met.
This is a risk amplifier for second-generation variants of the same general mechanism (polymer prodrug controlled release CNP agonists).
What likely carve-outs exist in the broader landscape
The claims as given do not include explicit carve-outs for:
- specific polymer chemistries beyond “water-soluble branched polymer” and hydrogel,
- specific L1 chemical classes beyond “reversible prodrug linker” and covalent/reversible conjugation to defined D positions,
- specific analytic characterization methods.
That means other patents in the landscape may still be required to fully police chemical space, but US 11,311,604 can already constrain the design space for any entrant whose system uses the same architectural and performance thresholds.
Key Takeaways
- US 11,311,604 claim 1 is a platform claim for controlled-release CNP agonist conjugates with free-form release, extended release half-life, and a quantified NPR-C IC50 shift versus free CNP, using a reversible prodrug linker (L1) and branched water-soluble polymer / hydrogel (Z / Z′) architecture.
- Claims 2 and 3 extend coverage to formulations and administration-based methods.
- Claims 4, 5, and 10 provide broad therapeutic use coverage across a large enumerated disease list, with specific dependent claims for achondroplasia and multiple craniosynostosis/apert-family syndromes.
- The enforceability and design-around risk is driven by three measurable requirements: release half-life, NPR-C IC50 ratio, and reversible linker + polymer/hydrogel architecture plus free-form release.
FAQs
1) Does US 11,311,604 claim require a specific CNP peptide sequence?
Yes and no: it permits any sequence from SEQ ID NO:1 through SEQ ID NO:95 as the CNP moiety (D), so it is sequence-permissive but sequence-bounded.
2) Is the NPR-C IC50 requirement part of claim 1 itself or only dependent claims?
It is part of claim 1. Dependent claims (6 and 7) raise the threshold to 20-fold and 50-fold, respectively.
3) What controls long-acting duration in the claim language?
Release half-life thresholds (≥ 6 hours in claim 1, and longer in claims 8 and 9) plus the polymer/hydrogel architecture and reversible prodrug linker system.
4) Are disease indications broad or limited?
They are broad. Claim 4 lists a large set of diseases treatable with a CNP agonist, while claims 5 and 10 target achondroplasia and specific craniosynostosis syndromes.
5) Is there coverage for both product and method-of-use?
Yes. Claim 1 covers the controlled-release agent; claims 2 covers composition; claims 3–5 and 10 cover methods for treating, controlling, delaying, or preventing disease in mammalian patients.
References
[1] US Patent 11,311,604. (n.d.). Claims text provided in the prompt.
