United States Patent 12,156,917: Scope, Claims, and US Patent Landscape for CNP Prodrugs for Growth Disorders
US Patent 12,156,917 protects a method of treating growth disorders associated with impaired C-type natriuretic peptide (CNP) signaling, including achondroplasia, hypochondroplasia, SHOX deficiency, and Noonan syndrome. The claims center on administering a CNP prodrug (or salt) built from (i) a defined CNP “ring” moiety with specific sequence requirements and (ii) a carrier-linked reversible prodrug linker system that conjugates to specific amino-acid residues on the CNP moiety through an amino-acid side chain chemistry. The scope is claim-dense around linker architecture (-L1- and -L2-), attachment sites, and carrier morphology (including branched polymer options).
What does US 12,156,917 claim, in forceable terms?
Core protected act
The independent claim is a treatment method:
Claim 1 defines the prodrug structure through three linked modules
Claim 1 ties infringement to a prodrug that includes:
-
CNP moiety -D
- Contains a ring moiety having the sequence of SEQ ID NO:96
- In dependent claim set, -D also has the sequence of SEQ ID NO:24 (claims 5 and 6).
-
Reversible prodrug linker -L1-
- A reversible prodrug linker moiety -L1- is:
- covalently and reversibly conjugated to either:
- a side chain of an amino acid residue of the ring moiety, or
- the backbone of the ring moiety.
-
Carrier moiety -Z conjugated through -L2- to -L1-
- Carrier moiety -Z is conjugated through -L2- to reversible linker -L1-.
- -L2- can be a chemical bond or a spacer (explicitly stated in claim 1).
Attachment restriction (“where on -D” the linker attaches)
- Claim 2 and 3 restrict -L1- attachment to the side chain rather than backbone.
- Claim 3 narrows the amino acid residue to:
- lysine
- serine
- aspartic acid
- arginine
- Claim 4 narrows further to:
- Claim 6 specifies:
- -D is SEQ ID NO:24 and -L1- is conjugated to lysine at position 26.
A specific structural negative condition
Claim 8 includes a prohibition consistent with a defined linker substitution pattern:
- In claim 8: “wherein the hydrogen marked with the asterisk in formula (II) is not replaced by -L2-Z.”
This is a typical “substitution must not occur at this position” limitation: it narrows the set of allowable -L1- variants that still fall inside the claimed formula.
How broad is the chemical scope of the CNP prodrug?
1) Breadth from modular definitions
The structure is modular. Claim 1 does not enumerate individual chemical identities for -L1- and -L2- beyond requiring:
- -L1- is reversible and is conjugated covalently to an amino acid side chain (or backbone).
- -L2- is a chemical bond or spacer.
That modular approach typically supports broad interpretation: many prodrug linkers can be argued as “reversible prodrug linkers,” and many spacer chemistries can be argued as “chemical bond or spacer,” unless the dependent claims narrow them further.
2) Claim 7 is a “formula gate” for -L1-
Claim 7 defines -L1- as being of formula (II), which contains extremely large definitional variables:
- Dashed line indicates attachment by forming an amide bond to nitrogen of an amino acid side chain.
- -X- and substituent groups include broad classes (alkyl, heterocycles, cycloalkyl, aryl and heteroaryl).
- “Optionally substituted” patterns and “wherein optionally pairs form chemical bonds” permit multiple ring closures.
This makes claim 7 a structure class claim rather than a single compound claim. The claim can cover many distinct -L1- scaffolds so long as they fit formula (II) and the attachment/substitution constraints (including the claim 8sterisk exclusion) are met.
3) Claim 8 further enumerates -L2- options
Claim 8 specifies -L2- can be selected from an enumerated set, including:
- bond and heteroatom-containing linkers:
- -T-
- -C(O)O-
- -O-
- -C(O)-
- -C(O)N(Ry1)-
- sulfonamide and sulfone derivatives:
- -S(O)2N(Ry1)-
- -S(O)N(Ry1)-
- -S(O)2-
- -S(O)-
- -N(Ry1)S(O)2N(Ry1a)-
- -N(Ry1)-
- and variations including carbamates/esters-like fragments such as -OC(ORy1)(Ry1a)-
- and also allows:
- C1-50 alkyl
- C2-50 alkenyl
- C2-50 alkynyl
- with optional substitution patterns and interruptions by multiple group types.
This creates a wide perimeter around what can be considered a permissible “spacer/carrier connector” between -L2- and -Z.
4) Carrier scope: claim 9-11
- Claim 9: -Z is a branched polymer.
- Claim 10: branched moiety -Z has MW 10 kDa to 80 kDa.
- Claim 11: -Z comprises a moiety of formula (a) with a branching point BPa and polymeric moiety -Pa′, -Pa″, -Pa′″.
The carrier language is narrower than the linker language: it requires a branched polymer and provides MW limits. That said, branched polymers within 10-80 kDa are still a large design space (and claim 11 indicates polymeric moiety types with flexible definitions).
Practical consequence
- Inside claim 1 scope: a method using CNP prodrugs where CNP moiety architecture and the reversible linker mechanism match.
- Further inside (depending on which dependent claims are asserted): additional restrictions on attachment residue (lysine, position 26), linker formula class (II), -L2- list, and carrier being a branched polymer with 10-80 kDa.
How does the claim set narrow disease indication and administration route?
Disease scope (indication)
Administration route
- Claim 13 limits administering to subcutaneous.
These dependent claim restrictions matter for design-around: a product still using the claimed prodrug chemistry could theoretically be argued outside if it uses an entirely different dosing method that does not satisfy claim 13, but claim 1 still contains no route limitation. So for infringement risk, route alone does not fully avoid claim 1 unless claim 1 is not met.
Is infringement likely to hinge on “SEQ ID NO” assignments and lysine position?
Yes, on paper the claim set creates a “two-step precision ladder.”
Sequence-based constraints
- Claim 1 requires:
- a ring moiety with SEQ ID NO:96
- Claim 5 requires:
- Claim 6 ties both:
- -D is SEQ ID NO:24
- -L1- is conjugated to lysine at position 26
Why this matters
- If a candidate prodrug does not satisfy SEQ ID NO:96 or SEQ ID NO:24 requirements for -D’s ring and sequence, it can fall outside the structural claim boundary.
- If attachment is not via a reversible conjugation to the correct amino-acid residue (lysine/serine/aspartic acid/arginine) and, in some dependent claims, lysine position 26, infringement risk drops against those dependent claims.
- Claim 1 still requires a reversible conjugation at an amino acid side chain or backbone. Many prodrug designs fail that “where the covalent bond sits” requirement.
Claim-by-claim scope map (what each claim adds)
| Claim |
Adds to independent claim 1 |
Scope effect |
| 1 |
Method for listed disorders; administer CNP prodrug/salt; requires CNP moiety -D with ring sequence SEQ ID NO:96; requires reversible linker -L1- conjugated to amino acid side chain/backbone; requires carrier -Z via -L2- |
Defines infringement perimeter: disease set + chemistry module set |
| 2 |
-L1- is conjugated to amino-acid side chain (not backbone) |
Narrows attachment locus |
| 3 |
Side chain amino acid is lysine/serine/aspartic acid/arginine |
Narrows attachment residue set |
| 4 |
Side chain amino acid is lysine |
Narrows residue to lysine only |
| 5 |
-D has SEQ ID NO:24 |
Narrows -D sequence |
| 6 |
-D = SEQ ID NO:24 and -L1- on lysine at position 26 |
Narrows to a specific attachment position |
| 7 |
-L1- must match formula (II) and attachment occurs by amide bond to nitrogen of amino-acid side chain |
Narrows reversible linker class to a defined scaffold family |
| 8 |
-L2- enumerated set; additional formula (II) substitution restriction |
Narrows spacer/linker-to-carrier connector chemistries |
| 9 |
-Z is branched polymer |
Narrows carrier morphology |
| 10 |
Branched -Z MW 10-80 kDa |
Narrows carrier size window |
| 11 |
-Z comprises a polymer branching formula (a) |
Narrows carrier structure form |
| 12 |
Disease is achondroplasia |
Narrows indication |
| 13 |
Administration is subcutaneous |
Narrows dosing route |
Where does this patent sit in the US patent landscape for CNP prodrugs in growth disorders?
Landscape framing: what the claim architecture indicates
A claim structure like this usually targets a specific prodrug design platform:
- CNP receptor pathway therapy: It protects prodrug forms of CNP for growth disorder indications.
- Prodrug reversibility: It protects prodrugs with reversible linker logic, not just permanent conjugates.
- Large carrier: It emphasizes polymer carriers (10-80 kDa branched polymer), which aligns with half-life extension strategies.
What other US patents commonly exist in this space
In practice, CNP prodrug and CNP analog IP clusters in the US tend to split across:
- peptide/analog composition claims,
- prodrug linker and conjugation chemistry claims,
- carrier (polymer, albumin binding, PEG or polymer scaffolds) claims,
- method of treatment claims for pediatric growth disorders.
This patent is concentrated in the method of treatment + prodrug structural platform overlap. That makes it especially relevant for:
- portfolio clearance for CNP prodrugs in US,
- generic or biosimilar-like development of prodrug conjugates,
- combination development where the prodrug chemistry does not change.
Competitive risk signal from claim depth
The claim set has nested narrowing provisions:
- specific CNP moiety sequence requirements,
- specific amino acid attachment residue and position,
- specific linker formulas,
- specific spacer connector lists,
- specific branched polymer MW.
This pattern often indicates the applicant expected multiple design variables but chose to lock down key chemical features needed for patentability, leaving a defined platform that the applicant can enforce against close variants.
Scope: design-around leverage points
Based solely on the claim language, the highest leverage design-around levers (those that can defeat claim 1 or major dependent claims) are:
-
Break the CNP moiety -D requirement
- Avoid the ring moiety sequence of SEQ ID NO:96 and/or -D = SEQ ID NO:24.
-
Break the reversible conjugation constraint
- If the chemistry is not “covalently and reversibly conjugated” to an amino acid side chain or backbone, claim 1 can fail.
-
Break the attachment residue or position
- If attachment is not via the side chain to lysine/serine/aspartic acid/arginine (or not lysine at position 26 for the dependent claims), dependent claims fall away.
-
Break the -L1- formula (II)
- Use a reversible linker scaffold that does not match formula (II) in claim 7, while still meeting the reversible functional requirement in claim 1 (this is harder because claim 1 does not require formula (II), but formula (II) becomes mandatory if claim 7 is asserted).
-
Break the carrier -Z platform
- Avoid a branched polymer carrier of 10-80 kDa (claims 9-10), and avoid the carrier formula (a) (claim 11).
-
Route (subcutaneous)
- Only impacts claim 13; does not remove claim 1 risk because claim 1 is route-agnostic.
Enforcement posture: likely claim assertions
From a litigation and licensing standpoint, enforcement typically starts with the broadest independent claim that has the least structural constraints beyond the core platform definitions.
- Primary infringement theory: claim 1
- Backup narrowing: claims 2-6 for attachment residue/position and sequence
- Secondary narrowing: claims 7-8 for linker/spacer specifics
- Carrier-specific: claims 9-11 for branched polymer carrier with MW window
- Narrow cover: claim 12 and 13 when targeting a product marketed specifically for achondroplasia with subcutaneous dosing.
Key Takeaways
- US 12,156,917 protects a method of treating multiple growth disorders (achondroplasia, hypochondroplasia, Noonan syndrome, SHOX deficiency, and “short stature”) by administering a CNP prodrug with a defined modular architecture: CNP ring sequence (SEQ ID NO:96) plus reversible covalent linker -L1- conjugated to a specific amino-acid site on the CNP moiety, plus carrier -Z connected through -L2-.
- The claim set is chemistry-dense: dependent claims narrow to -D = SEQ ID NO:24, lysine attachment at position 26, -L1- formula (II), -L2- enumerated connector classes, and a branched polymer carrier with 10-80 kDa MW and a defined carrier branching formula.
- Competitive risk is highest for products using CNP prodrugs with reversible linkers and polymer carriers that are designed to match this exact platform (especially attachment chemistry and carrier MW/morphology).
- Route- and indication-specific dependent claims (achondroplasia; subcutaneous) provide additional enforcement hooks but do not remove coverage risk from the route-agnostic independent claim 1.
FAQs
-
What is the main infringement element in US 12,156,917?
Administering a therapeutically effective amount of a CNP prodrug (or salt) with the claimed CNP moiety, reversible linker attachment to the amino-acid side chain/backbone, and a carrier conjugated through -L2-.
-
Does the patent require subcutaneous dosing?
Only claim 13 requires subcutaneous dosing. Claim 1 is not route-limited.
-
Which CNP moiety sequence constraints apply?
Claim 1 requires a ring moiety with SEQ ID NO:96. Claims 5 and 6 require -D = SEQ ID NO:24, with lysine position 26 as an added narrowing.
-
What does the claim set say about the linker -L1-?
Claim 7 requires -L1- to match formula (II), with an amide-bond attachment to nitrogen of an amino-acid side chain and additional substitution constraints in claim 8.
-
How does the patent define the carrier -Z?
The carrier is a branched polymer (claim 9) with MW 10-80 kDa (claim 10), with additional structural definition in claim 11 via formula (a).
References
[1] US Patent 12,156,917. Claims provided in prompt text.
