Details for Patent: 11,311,604

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Which drugs does patent 11,311,604 protect, and when does it expire?

Patent 11,311,604 protects YUVIWEL and is included in one NDA.

This patent has seventeen patent family members in eleven countries.

Summary for Patent: 11,311,604

Title:	Controlled-release CNP agonists with low NPR-C binding
Abstract:	The present invention relates to a controlled-release CNP agonist having low NPR-C affinity; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.
Inventor(s):	Harald Rau, Ulrich Hersel, Kennett Sprogøe, Frank FALTINGER, Thomas Wegge, Felix Cleemann
Assignee:	Ascendis Pharma Endocrinology Division AS
Application Number:	US16/066,980
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 11,311,604: Controlled-Release CNP Agonists, Claim Scope and Patent Landscape

US Patent 11,311,604 protects controlled-release conjugates of C-type natriuretic peptide, or CNP, designed to release the active peptide in free form over at least six hours while reducing binding to the NPR-C clearance receptor. The broadest claim covers CNP agonists linked through reversible prodrug chemistry to a water-soluble branched polymer or hydrogel. Dependent claims extend the release period to 24 hours and 168 hours, increase NPR-C selectivity thresholds to 20-fold and 50-fold, and cover treatment of achondroplasia and a wide range of skeletal-growth disorders.

The patent is commercially relevant to long-acting CNP programs, including products intended to compete with or improve on daily CNP therapy. Its strongest protection is directed to the combination of peptide identity, reversible linker architecture, polymer or hydrogel attachment, pharmacokinetic release, and NPR-C avoidance. The claims do not cover every long-acting CNP molecule. A competing product that uses a different peptide, a nonreversible modification, a different release mechanism, or a different biological clearance profile may avoid literal infringement.

What does US Patent 11,311,604 protect?

The patent contains four principal protection layers:

Protection layer	Relevant claims	Scope
Controlled-release CNP conjugate	1, 6-9	CNP agonist conjugates meeting release and NPR-C activity criteria
Pharmaceutical composition	2	The claimed conjugate with at least one excipient
Therapeutic method	3-5, 10	Administration for CNP-responsive diseases, especially achondroplasia
Technical platform	1, 6-9	Reversible linker, branched water-soluble polymer, hydrogel, and extended release

Claim 1 is the central composition-of-matter claim. It requires all of the following:

1. A CNP agonist.
2. Release of the agonist in free form.
3. A release half-life of at least six hours under physiological conditions.
4. An IC50 against NPR-C at least five times higher than that of the corresponding free CNP agonist.
5. A specified conjugate arrangement involving:
   • a CNP peptide;
   • a reversible prodrug linker;
   • a spacer or chemical bond;
   • a water-soluble branched polymer or hydrogel; and
   • attachment to the ring moiety or backbone of the CNP peptide.

The claim covers conjugates represented by formulas (Ia) and (Ib), as well as a broader conjugate described as D-L. The variables x and y permit multiple linker or polymer substitutions:

• x: 1 to 16;
• y: 1 to 5.

That range potentially covers mono-, multi-, and highly substituted peptide conjugates, subject to the structural requirements and functional performance limitations.

How broad is the CNP sequence coverage?

Claim 1 identifies 95 CNP sequences through SEQ ID NOs:1-95. The claim therefore is not limited to native human CNP alone. It reaches a defined sequence genus consisting of the listed native, modified, truncated, substituted, or otherwise engineered CNP agonist sequences disclosed in the patent.

The scope depends on the actual content of SEQ ID NOs:1-95. Sequence-based infringement analysis must compare the accused peptide against each listed sequence and any applicable claim-construction principles. The claim does not expressly cover every peptide that activates NPR-B or every peptide described commercially as a CNP agonist.

The sequence limitation creates both value and vulnerability:

• Value: the patent can cover multiple CNP analogs and may prevent simple sequence substitutions from avoiding the patent.
• Vulnerability: a competitor using a CNP agonist outside SEQ ID NOs:1-95 could challenge literal infringement, although doctrine-of-equivalents issues may remain.

What does the reversible linker limitation require?

The linker limitation is central to the patent's technical scope. The claim requires L1 to be a reversible prodrug linker covalently and reversibly conjugated to either:

• the side chain of an amino acid residue in the CNP ring moiety; or
• the backbone of the ring moiety.

The linkage must permit release of the CNP agonist in free form under physiological conditions. A permanent PEGylated peptide, a stable covalent analog that does not regenerate free CNP, or a formulation that releases intact conjugate rather than free CNP may fall outside this limitation.

The patent therefore differs from conventional long-acting peptide designs based solely on:

• permanent PEGylation;
• albumin binding;
• depot injection;
• crystalline suspension;
• microspheres;
• fatty-acid conjugation; or
• nonreversible peptide sequence engineering.

The infringement question will turn on whether the accused product contains a chemically reversible bond meeting the claim's functional and structural requirements.

What polymers and hydrogels are covered?

Claim 1 identifies two principal long-acting carrier categories.

Water-soluble branched polymers

Z is a water-soluble branched polymer whose first branching point is less than 50 atoms from the CNP moiety. This limitation narrows the claim to a relatively proximal branched architecture. It is not a generic claim to every PEGylated peptide.

Potentially relevant polymers include branched PEG or other water-soluble polymer structures if they satisfy the branching-distance requirement and are attached through the claimed linker arrangement. Linear polymers may not satisfy the express branched-polymer limitation unless they are used in an alternative claimed embodiment.

The less-than-50-atom limitation creates a measurable structural test. Chemical structures, linker drawings, analytical characterization, and manufacturing specifications would be important in a freedom-to-operate review.

Hydrogels

The alternative Z' element is a hydrogel. A hydrogel embodiment may be particularly relevant to injectable depot products or formulations designed for extended release.

The claim language appears to require the hydrogel in the claimed conjugate architecture, not merely as an unrelated excipient in a formulation. A product that places an unmodified CNP agonist inside a hydrogel matrix may present a different infringement analysis from a CNP agonist covalently linked through L1-L2 to the hydrogel.

What pharmacokinetic and receptor requirements limit the claims?

The patent combines structural limitations with two functional requirements.

Release half-life

Claim 1 requires a release half-life of at least six hours under physiological conditions. Claim 8 raises the threshold to at least 24 hours, and claim 9 raises it to at least 168 hours.

Claim	Minimum release half-life
1	6 hours
8	24 hours
9	168 hours

The phrase "under physiological conditions" requires a defined testing environment. Relevant variables may include:

• pH;
• temperature;
• buffer composition;
• plasma or serum matrix;
• enzyme content;
• species;
• peptide concentration; and
• analytical method used to distinguish free CNP from conjugated CNP.

A product could satisfy the six-hour claim but fail the 24-hour or 168-hour dependent claims. Conversely, a product with a long in vivo half-life may not satisfy a claim directed to release half-life if the release assay measures a different parameter.

NPR-C receptor activity

The controlled-release conjugate must have an IC50 against NPR-C that is at least five times higher than the corresponding free CNP agonist. Claims 6 and 7 raise the ratio to at least 20-fold and 50-fold.

Claim	Minimum increase in NPR-C IC50
1	5-fold
6	20-fold
7	50-fold

This limitation is intended to reduce NPR-C-mediated clearance while preserving delayed generation of active free CNP. It creates a substantial evidentiary issue because the ratio must be measured against the "corresponding free CNP agonist" using comparable assay conditions.

A competitor may avoid the claim if its conjugate:

• does not show the required NPR-C IC50 shift;
• releases an active analog rather than the corresponding free CNP agonist;
• uses a different receptor-selectivity mechanism; or
• cannot be shown to meet the claimed ratio under a properly comparable assay.

Which diseases and uses are covered?

Claim 3 broadly covers treatment, control, delay, or prevention of diseases treatable with a CNP agonist. Claim 4 lists a long set of skeletal, cartilage, growth, and developmental disorders. Claim 5 specifically covers achondroplasia. Claim 10 covers several craniosynostosis and skeletal syndromes, including:

• Muenke syndrome;
• Crouzon syndrome;
• Apert syndrome;
• Jackson-Weiss syndrome;
• Pfeiffer syndrome; and
• Crouzondermoskeletal syndrome.

The method claims are broad in disease category but remain dependent on use of the controlled-release CNP agonist of claim 1. They do not independently cover treatment with unmodified CNP, vosoritide, or any CNP agonist lacking the claimed conjugate features.

The achondroplasia claim has the greatest commercial relevance because achondroplasia is the leading clinical indication for CNP agonists and the indication associated with FDA-approved vosoritide.

When does US Patent 11,311,604 lose exclusivity?

The patent's statutory term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable priority issues. Public patent records identify the patent as part of a CNP controlled-release patent family with a priority chain predating issuance.

A reliable expiration analysis must distinguish:

Term issue	Commercial effect
Basic 20-year term	Sets the ordinary end of patent protection
Patent-term adjustment	Can extend the expiration date for USPTO delay
Patent-term extension	Potentially available for qualifying regulatory delay
Terminal disclaimer	Can shorten the term if the patent is tied to another patent
Continuation practice	May produce related patents with different claim scope
Foreign counterparts	May expire on different dates because of national rules

The issue date, April 26, 2022, does not determine the expiration date. The relevant date is the earliest effective nonprovisional priority date, plus any adjustment or extension. Patent 11,311,604 should not be treated as expiring in 2042 merely because it issued in 2022.

What is the Orange Book and FDA status?

US Patent 11,311,604 is directed to a peptide or biologic-style CNP conjugate rather than a conventional small-molecule drug product. The principal FDA exclusivity framework for an approved CNP biologic is the Biologics Price Competition and Innovation Act, or BPCIA, rather than ordinary Hatch-Waxman Orange Book litigation.

Voxzogo, the marketed vosoritide product, was approved by FDA under a biologics license application for pediatric patients with achondroplasia whose epiphyses are not closed (FDA, 2021). A follow-on sponsor would generally evaluate:

• Purple Book reference-product status;
• 351(k) biosimilar or interchangeable pathway;
• BPCIA patent-exchange procedures;
• patent infringement under 35 U.S.C. §271(e)(2);
• regulatory exclusivity; and
• manufacturing comparability.

An Orange Book listing should not be assumed for this patent. Orange Book status depends on the approved application and sponsor-submitted patent information, while biologic patent strategy commonly relies on BPCIA disclosures, licensing records, patent-family analysis, and district-court litigation rather than a conventional Orange Book listing.

Which companies are commercially exposed?

Ascendis Pharma is the most directly relevant commercial entity because its TransCon technology is designed to provide sustained release of peptide therapeutics through reversible conjugation chemistry. Ascendis has developed TransCon CNP, also known as navepegritide, for achondroplasia and other skeletal disorders.

BioMarin Pharmaceutical is the principal commercial company associated with vosoritide and Voxzogo. Vosoritide is a modified CNP analog administered as a daily injection. Its commercial product profile differs from a long-acting reversible CNP conjugate.

Program	Company	Product concept	Relevance to Patent 11,311,604
TransCon CNP / navepegritide	Ascendis Pharma	Long-acting, transiently conjugated CNP	Potentially close technical and claim overlap
Voxzogo / vosoritide	BioMarin	Daily CNP analog	Competes clinically but may not practice the claimed conjugate
Other CNP programs	Various biotechnology companies	Native or engineered CNP agonists	Risk depends on sequence, linker, carrier, and release profile

Commercial competition does not establish patent infringement. A daily free-peptide product may compete with a claimed long-acting conjugate without falling within claim 1.

How strong is the patent estate?

The patent has meaningful claim breadth, but its enforceability depends on proving several technical elements simultaneously.

Strengths

• Broad disease coverage anchored by achondroplasia.
• Coverage of 95 disclosed CNP sequences.
• Functional release threshold beginning at six hours.
• Functional NPR-C selectivity threshold beginning at five-fold.
• Coverage of multiple linker substitution counts.
• Claims directed to composition, formulation, and treatment.
• Potential applicability to both polymer and hydrogel embodiments.
• Protection aimed at a clinically valuable long-acting CNP profile.

Weaknesses and design-around routes

• Claim 1 requires release of free CNP, which may exclude alternative active-release mechanisms.
• The polymer embodiment requires a branched polymer with a branching point less than 50 atoms from CNP.
• The linker must be reversible and attached to a defined region of the peptide.
• The claim depends on comparative IC50 testing against the corresponding free agonist.
• The sequence list may exclude novel CNP agonists outside SEQ ID NOs:1-95.
• A nonconjugated depot formulation may avoid the conjugate limitation.
• A permanent conjugate may avoid the reversible-linker limitation.
• A product with a different release mechanism may avoid the release-half-life limitation.

The strongest invalidity challenges would likely concern written description, enablement, indefiniteness of functional testing terms, anticipation by earlier CNP conjugate disclosures, and obviousness based on known long-acting peptide technologies. The patent holder would counter that the claimed combination requires a specific and nonpredictable balance of delayed free-peptide release and reduced NPR-C binding.

What generic or biosimilar entry risks exist?

For a long-acting CNP conjugate, ordinary generic substitution is unlikely to be the principal entry route. The competitive pathway depends on the reference product and the regulatory classification of the product being challenged.

Potential entry scenarios are:

Entry scenario	Patent risk
Same CNP sequence and reversible branched-polymer conjugate	High potential risk
Same sequence with a permanent polymer attachment	Claim 1 design-around potential
Hydrogel-linked CNP with reversible release	Material risk under hydrogel embodiment
Daily free CNP or CNP analog	Lower risk under these claims
Novel CNP sequence outside SEQ ID NOs:1-95	Literal infringement risk may decline
Nonconjugated injectable depot	Depends on whether the product practices the claimed conjugate
Biosimilar or interchangeable product	BPCIA patent-resolution risk, subject to reference-product classification

A biosimilar sponsor would need to analyze not only patent 11,311,604 but the entire family, including continuation and divisional patents directed to particular linker chemistries, sequences, formulations, methods, and manufacturing processes.

What litigation and settlement issues matter?

The supplied claim set does not establish that patent 11,311,604 has been asserted in a specific lawsuit or included in a settlement. Litigation risk should be evaluated at the patent-family level because a commercial product may be challenged under several related patents at once.

The principal litigation issues would include:

1. Claim construction for "free form."
2. Meaning of "release half-life."
3. Meaning of "under physiological conditions."
4. Determination of the corresponding free CNP agonist.
5. NPR-C IC50 assay comparability.
6. Whether the accused linker is reversible.
7. Distance calculation for the first polymer branching point.
8. Whether the accused peptide matches one of SEQ ID NOs:1-95.
9. Written-description support for the full sequence and polymer scope.
10. Enablement of the 168-hour release embodiment.

Settlement agreements involving CNP products would likely address patent-family licenses, geographic rights, launch dates, regulatory approvals, and treatment of continuation patents. A settlement limited to one patent would not necessarily clear the full CNP platform estate.

How does this patent compare with conventional vosoritide protection?

Patent 11,311,604 is platform-oriented. It protects a long-acting conjugate architecture and performance profile. Vosoritide protection, by contrast, may focus on the peptide sequence, formulation, dosing regimen, manufacturing process, or therapeutic use.

Issue	Patent 11,311,604	Conventional vosoritide patent strategy
Core subject	Controlled-release CNP conjugate	CNP analog, formulation, use, or dosing
Administration profile	Intended for extended release	Daily administration for marketed vosoritide
Key receptor issue	Reduced NPR-C binding	Native pharmacology of the administered analog
Main infringement proof	Structure plus release and IC50 data	Sequence, formulation, dose, or use
Primary regulatory context	Biologic and platform competition	BLA, biologic exclusivity, and BPCIA
Main design-around	Change linker, polymer, sequence, or release mechanism	Change sequence, formulation, or regimen

Key Takeaways

• US Patent 11,311,604 is directed to long-acting CNP agonist conjugates that release free CNP under physiological conditions.
• Claim 1 requires both a release half-life of at least six hours and at least a five-fold increase in NPR-C IC50 versus the corresponding free agonist.
• The patent covers 95 specified CNP sequences, reversible prodrug linkers, branched water-soluble polymers, and hydrogels.
• Dependent claims extend protection to 24-hour and 168-hour release and to 20-fold and 50-fold NPR-C IC50 increases.
• Achondroplasia is the commercially central method-of-treatment indication.
• The patent is more relevant to long-acting conjugated CNP products than to daily free CNP or conventional CNP analogs.
• Literal infringement risk declines materially for products using a sequence outside SEQ ID NOs:1-95, a permanent linker, a nonconjugated depot, or a release mechanism that does not regenerate free CNP.
• Orange Book treatment should not be assumed because CNP products are regulated in the biologic environment, where BPCIA and Purple Book issues may be more relevant.
• A complete freedom-to-operate review requires the entire continuation and foreign patent family, not patent 11,311,604 in isolation.

FAQs About US Patent 11,311,604

Does US Patent 11,311,604 cover vosoritide itself?

Not necessarily. The claims target controlled-release conjugates containing specified CNP agonist sequences and reversible linker-polymer or hydrogel architectures. A daily administered vosoritide product without the claimed conjugate structure may fall outside the patent.

Does the patent cover PEGylated CNP?

Only potentially. The PEG or other water-soluble polymer must satisfy the claimed branched-polymer structure, branching-distance limitation, reversible linker requirement, and release and NPR-C performance thresholds.

Can a competitor avoid the patent by using a different CNP sequence?

Potentially. Literal infringement depends on whether the sequence falls within SEQ ID NOs:1-95 or an applicable claim interpretation. A sequence outside the listed group may provide a design-around, subject to equivalence and related-family claims.

Does the 168-hour claim require weekly dosing?

No. Claim 9 requires a release half-life of at least 168 hours under physiological conditions. It does not expressly require a weekly dosing schedule, clinical dosing interval, or particular administration frequency.

Is this patent relevant to biosimilar litigation?

Yes, if a competing product is regulated through a biologic pathway and practices the claimed CNP conjugate technology. The relevant process may involve BPCIA patent disclosures and litigation rather than a conventional Orange Book Paragraph IV filing.

References

1. United States Patent and Trademark Office. (2022). US Patent No. 11,311,604, Controlled-release CNP agonists.

2. U.S. Food and Drug Administration. (2021). FDA approves first drug for children with achondroplasia, a rare disorder of bone growth. FDA.

3. U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products. FDA.

4. Biologics Price Competition and Innovation Act of 2009, 42 U.S.C. § 262.

5. Patent Act, 35 U.S.C. §§ 154, 271, 282.

Drugs Protected by US Patent 11,311,604

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ascendis	YUVIWEL	navepegritide	POWDER;SUBCUTANEOUS	219164-001	Feb 27, 2026		RX	Yes	Yes			Y	Y		INCREASE OF LINEAR GROWTH IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH ACHONDROPLASIA WITH OPEN EPIPHYSES
Ascendis	YUVIWEL	navepegritide	POWDER;SUBCUTANEOUS	219164-002	Feb 27, 2026		RX	Yes	Yes			Y	Y		INCREASE OF LINEAR GROWTH IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH ACHONDROPLASIA WITH OPEN EPIPHYSES
Ascendis	YUVIWEL	navepegritide	POWDER;SUBCUTANEOUS	219164-003	Feb 27, 2026		RX	Yes	Yes			Y	Y		INCREASE OF LINEAR GROWTH IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH ACHONDROPLASIA WITH OPEN EPIPHYSES

International Family Members for US Patent 11,311,604

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017205694
Australia	2022221482
Brazil	112018011008
Canada	3007987
China	108472383