Details for Patent: 10,442,846

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Which drugs does patent 10,442,846 protect, and when does it expire?

Patent 10,442,846 protects MIMRYLO and is included in one NDA.

This patent has twenty-eight patent family members in twenty countries.

Summary for Patent: 10,442,846

Title:	Hepcidin analogues and uses thereof
Abstract:	The present invention relates, inter alia, to certain hepcidin peptide analogs, including peptides and dimers thereof, and to the use of the peptides and peptide dimers in the treatment and/or prevention of a variety of diseases, conditions or disorders, including treatment and/or prevention of iron overload diseases, which include hereditary hemochromatosis and iron-loading anemias, and other conditions and disorders described herein.
Inventor(s):	Mark Leslie Smythe, Gregory Thomas Bourne, Simone Vink, Brian Troy Frederick, Praveen Madala, Anne Pernille Tofteng Shelton, Jacob Ulrik Fog
Assignee:	Protagonist Therapeutics Inc
Application Number:	US16/037,982
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 10,442,846: Hepcidin-Mimetic Peptide Claims, Patent Scope, Exclusivity and Generic Risk

US Patent 10,442,846 protects a broad genus of synthetic hepcidin mimetics designed to bind ferroportin and treat iron-overload diseases. Its independent peptide claim covers variable amino-acid sequences, terminal modifications, PEGylation, disulfide-bonded cysteine structures, salts and solvates. Dependent claims narrow the genus toward defined X′ and Y′ sequence families, while the method claims cover hereditary hemochromatosis, transfusional iron overload and thalassemia.

The patent is commercially relevant to rusfertide, also known as PTG-300, because rusfertide is a long-acting hepcidin mimetic developed for diseases involving excess iron or dysregulated iron metabolism. The claims provided do not identify a single marketed drug sequence. Whether a particular clinical candidate falls within the claims requires an exact sequence and chemical-structure comparison.

What does US Patent 10,442,846 cover?

The patent covers four related subject-matter categories:

1. Synthetic peptide compounds and their salts or solvates.
2. Pharmaceutical compositions containing those peptides.
3. Methods of treating iron-metabolism diseases.
4. Peptides that exhibit hepcidin activity or bind ferroportin.

Claim 1 is the central composition-of-matter claim. It covers a peptide with the structure:

R1′-X′-Y′-R2′

The molecule contains:

• An N-terminal group, R1′.
• An X′ peptide segment of up to 10 positions.
• A Y′ peptide segment of up to 15 positions.
• A C-terminal amide or acid group, R2′.
• Optional PEGylation on X′ or Y′.
• At least one cysteine among specified Y′ positions.
• Disulfide linkage when two or more cysteine residues are present.

The claim permits extensive sequence variation. It also permits nonstandard amino acids and D-amino acids, including Aib, Dpa, bhAsp, bhPhe, bhPro, Ida, D-Asp, D-Thr, D-His, D-Pro, D-Ile, D-Cys, D-Phe, D-Lys and D-Arg.

How broad is claim 1 of US 10,442,846?

Claim 1 is broad in chemical space but constrained by a defined sequence architecture.

X′ segment

X′ has 10 indexed positions, X1 through X10. Each position has a closed list of permitted residues, with some positions allowing the residue to be absent. The segment includes sequence motifs associated with hepcidin activity, including variants around:

• Asp-Thr-His-Phe-Pro-Ile-Cys-Ile-Phe-Lys
• Asp-Thr-His-Phe-Pro-Cys-Ile-Ile-Phe-Lys
• Related D-amino-acid, beta-amino-acid and noncanonical-residue variants

Claims 3 through 5 narrow this portion. Claim 4 limits X′ to a more recognizable scaffold in which positions X2 and X3 are Thr and His, respectively, and X9 is Phe. Claim 5 narrows the sequence further by requiring Cys at X6 and Ile at X7.

Y′ segment

Y′ contains up to 15 positions and provides the cysteine-rich structural component. The claim requires at least one cysteine at Y1, Y2, Y8, Y9, Y11, Y13 or Y14.

Claims 6 through 9 define increasingly specific Y′ families. Claim 8, for example, requires a sequence with cysteine at Y2 and Y9, subject to additional variable positions. Claim 9 narrows the structure to:

Val-Cys-Y3-His-Arg-Y6-Y7-Y8-Cys-Tyr-Arg-Y12-Y13-Y14-Y15

This creates a defined cysteine-rich hepcidin-mimetic topology rather than an unrestricted peptide.

Terminal modifications

R1′ may be hydrogen, alkyl, aryl, arylalkyl, alkanoyl or pGlu. Claim 2 limits the N-terminal group to hydrogen, isovaleric acid, isobutyric acid or acetyl.

R2′ may be -NH2 or -OH, creating an important distinction between amidated and free-acid forms.

PEGylation

The claim permits PEGylation on X′ or Y′. This limitation is commercially significant because PEGylation can extend systemic exposure and support less frequent dosing. A PEGylated product may infringe even when its unmodified peptide sequence differs from a disclosed lead compound, provided the full claimed sequence architecture is met.

What do claims 3 through 9 add?

The dependent claims create a layered fallback structure.

Claim	Primary limitation	Commercial significance
1	Broad X′/Y′ peptide genus, cysteine requirement, optional PEGylation and disulfide bond	Principal composition-of-matter protection
2	Narrow N-terminal groups	Captures common acylated or unmodified forms
3	Narrower residue choices throughout X′	Reduces sequence breadth
4	X′ motif with Thr-His and terminal Phe	Covers a defined hepcidin-mimetic scaffold
5	X′ includes Cys-Ile in positions X6-X7	Narrows the disulfide-capable X′ structure
6	Defined 10-position Y′ family	Protects a specific cysteine-containing fragment
7	Defined Y′ motif with Ser-Lys-Gly-Trp and Cys	Provides another sequence fallback
8	15-position cysteine-rich Y′ family	Protects a more extended disulfide-containing structure
9	Highly specified Val-Cys-His-Arg-Cys-Tyr-Arg motif	Strongest sequence-specific fallback
10	Peptide exhibits hepcidin activity	Functional limitation
11	Peptide binds ferroportin	Target-based functional limitation

Claims 10 and 11 are narrower than claim 1 because they require biological activity or ferroportin binding. They may assist enforcement against structurally close molecules that satisfy the sequence limitations but dispute activity. Their practical value depends on how the court construes the functional language and what assay evidence establishes hepcidin activity or ferroportin binding.

What diseases are protected by the method claims?

Claim 13 covers treatment of diseases associated with deficient hepcidin activity or excess iron. The listed conditions include:

• Hereditary hemochromatosis.
• HFE mutation hemochromatosis.
• Ferroportin mutation hemochromatosis.
• Transferrin receptor 2 mutation hemochromatosis.
• Hemojuvelin mutation hemochromatosis.
• Hepcidin mutation hemochromatosis.
• Juvenile and neonatal hemochromatosis.
• Hepcidin deficiency.
• Transfusional iron overload.
• Thalassemia.

Claims 14 through 19 narrow the disease categories, including transfusional iron overload, hereditary hemochromatosis and beta-thalassemia.

The method claims are relevant even if a competing product avoids literal infringement of the composition claims. A competing peptide could face method-of-use exposure if it is administered for a claimed disease and satisfies the claim 1 structural limitations.

What formulations are protected by US 10,442,846?

Claim 12 protects a composition containing at least one peptide of claim 1. The claim does not recite a specific excipient, dosage form, concentration, route of administration, release profile or device.

The patent therefore does not appear, from the claims supplied, to provide dedicated protection for:

• A particular prefilled syringe.
• A specific autoinjector.
• A defined liquid formulation.
• A lyophilized formulation.
• A particular buffer system.
• A sustained-release depot.
• A specific PEG linker or PEG molecular weight.
• A defined dose or dosing interval.

Its formulation protection is composition-by-inclusion. A formulation containing a covered peptide may fall within claim 12 even when the formulation itself is not separately claimed.

Is rusfertide covered by this patent?

Rusfertide, or PTG-300, is a synthetic hepcidin mimetic developed by Protagonist Therapeutics for iron overload and related hematologic disorders. Clinical development has focused on polycythemia vera and other settings in which hepcidin modulation can reduce iron availability or erythropoietic drive [2][3].

The patent’s X′ and Y′ architecture is consistent with a hepcidin-mimetic platform. That relationship does not, by itself, establish that every rusfertide formulation or clinical presentation falls within claim 1. Coverage depends on:

• The exact amino-acid sequence.
• The identity and placement of noncanonical residues.
• The N-terminal group.
• Whether the molecule is amidated or free acid.
• The PEG attachment site and linker.
• The cysteine disulfide pattern.
• Whether the commercial product uses a salt or solvate.

A sequence-level comparison is required to determine literal infringement. The broad genus may also raise infringement concerns under the doctrine of equivalents, although equivalence for peptide substitutions, PEGylation and disulfide geometry is fact-dependent.

When does US Patent 10,442,846 lose exclusivity?

The patent issued on October 15, 2019, as US Patent No. 10,442,846 [1]. The nominal patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers under the Patent Act.

Public patent-family records associate the patent with a priority date in 2015. On that basis, the nominal expiration is expected in 2035, before any adjustment under 35 U.S.C. §§ 154 or 156. The exact expiration date should be taken from the USPTO Patent Center patent-term calculation rather than inferred solely from the issue date [1].

Event	Date or status
Earliest reported priority period	2015
US patent grant	October 15, 2019
Nominal 20-year term	Expected in 2035
Patent-term adjustment	Must be confirmed in USPTO records
Patent-term extension for an approved product	No extension established from the claims supplied
Patent status	Issued patent; enforceability depends on maintenance and legal status

The patent’s remaining commercial value depends heavily on whether continuation patents, formulation patents or later sequence patents extend protection beyond the expected 2035 baseline.

What is the Orange Book status of US 10,442,846?

US 10,442,846 is not an Orange Book listing based on the patent claims and product status described here. The Orange Book lists patents associated with approved drug products under FDA-administered drug applications. Rusfertide was not an FDA-approved product in the public development record available for this analysis [4].

If rusfertide or another product covered by the patent receives approval under an NDA, the sponsor may seek Orange Book listing for patents that claim the drug substance, drug product or approved method of use. The FDA Orange Book process would then affect Abbreviated New Drug Application applicants and Paragraph IV certification strategy.

The patent is not itself a regulatory exclusivity right. Patent protection and FDA exclusivity would operate independently.

What Paragraph IV challenges and generic-entry risks exist?

No approved reference product and no public ANDA Paragraph IV dispute are established for the unapproved rusfertide program. A Paragraph IV challenge would become relevant only after FDA approval of a reference-listed drug and listing of relevant patents.

A generic or follow-on peptide entrant would face several barriers:

1. Exact sequence characterization.
2. Demonstration of pharmaceutical equivalence.
3. Analytical comparability for disulfide connectivity and PEGylation.
4. Bioavailability and immunogenicity requirements.
5. Potential infringement of claim 1 or its sequence-specific dependent claims.
6. Method-of-use exposure for iron-overload indications.
7. Manufacturing constraints associated with cysteine oxidation and PEG conjugation.

For a chemically synthesized peptide, a 505(b)(2) application may be more realistic than a conventional ANDA if the product differs in formulation, route, delivery system or clinical evidence requirements. FDA classification would depend on the final product and reference-product status.

Does this patent create biosimilar risk?

The traditional biosimilar pathway under section 351(k) is designed for biological products licensed under the Public Health Service Act. A synthetic peptide such as rusfertide may instead proceed through the Federal Food, Drug, and Cosmetic Act, depending on FDA classification and product characteristics.

The main competitive risk is therefore likely to arise from peptide follow-on products, 505(b)(2) applicants or other synthetic hepcidin mimetics rather than conventional biosimilars. A competing molecule could avoid literal infringement by changing the sequence, cysteine placement, PEG attachment or terminal chemistry, but those changes may reduce activity, stability or half-life.

How strong is the patent estate?

The patent is strongest against products that preserve the claimed hepcidin-mimetic architecture.

Strengths

• Broad Markush coverage across X′ and Y′.
• Protection for noncanonical and D-amino-acid substitutions.
• Explicit coverage of PEGylated molecules.
• Disulfide-bond requirement aligned with hepcidin-like structure.
• Composition, activity and ferroportin-binding claims.
• Method claims covering multiple iron-overload diseases.
• Sequence-specific dependent claims that may survive partial invalidity attacks.

Vulnerabilities

• Large genus claims may face written-description and enablement scrutiny if the disclosed examples do not reasonably support the full claimed sequence space.
• Functional limitations such as "exhibits hepcidin activity" and "binds ferroportin" may create claim-construction disputes.
• The claim uses extensive Markush alternatives, increasing both scope and potential prosecution-history estoppel.
• Claim 5 contains an apparent drafting error, referring to "claim h" and "formula or I′." The error may be correctable through claim construction or prosecution history, but it creates avoidable litigation risk.
• The patent does not, on the supplied claims, separately protect a defined commercial formulation, delivery device or manufacturing process.

The estate is materially stronger if continuation patents protect the specific clinical molecule, PEG linker, formulation and dosing regimen.

What manufacturing and intellectual-property barriers affect competitors?

The claim language identifies several technical barriers:

• Controlled synthesis of long, cysteine-containing peptides.
• Selective protection and deprotection of cysteine residues.
• Reproducible disulfide pairing.
• Control of oxidation-related impurities.
• Site-specific PEG conjugation.
• Removal of sequence-related impurities.
• Demonstration of consistent bioactivity and ferroportin binding.
• Control of aggregation and immunogenicity.

These technical barriers may delay entry even when a competitor develops a noninfringing sequence. They can also support regulatory differentiation where the follow-on product is not identical in sequence or postsynthetic modification.

Which companies are challenging the patent?

No public Paragraph IV challenge, ANDA litigation or settlement agreement is established for US 10,442,846 in the information reviewed. Protagonist Therapeutics is the principal company associated with rusfertide development, while Takeda Pharmaceutical has been involved in the clinical and commercial development relationship for rusfertide [2][3].

No conclusion should be drawn that the absence of an identified challenge eliminates future litigation risk. The relevant trigger would be FDA approval, Orange Book listing and filing of a competing application.

How does US 10,442,846 compare with competing hepcidin programs?

Program or approach	Modality	Target	Patent risk relative to US 10,442,846
Rusfertide/PTG-300	PEGylated synthetic hepcidin mimetic	Ferroportin and systemic iron regulation	Potentially high if sequence and PEG architecture fall within claim 1
Minihepcidin analogues	Short synthetic peptides	Ferroportin	Variable; sequence and disulfide topology determine overlap
Antisense or RNA approaches	Nucleic-acid therapy	Hepcidin or iron-regulatory pathways	Generally outside the peptide claims
Anti-ferroportin antibodies	Biologic antibody	Ferroportin	Generally outside the claimed peptide genus
Oral iron-regulation drugs	Small molecules	Hepcidin, ferroportin or upstream pathways	Usually outside the composition claims, but may compete commercially
Iron chelators	Small molecules	Circulating or stored iron	Outside the claims and commercially substitutive

The patent has more relevance to peptide competitors than to antibody, RNA or small-molecule programs.

What is the commercial exposure?

The commercial exposure is tied to the size of the addressable population and the indications selected for approval. Potential markets include polycythemia vera, beta-thalassemia, transfusional iron overload and hereditary hemochromatosis. Clinical development and regulatory progress determine whether the patent produces product revenue.

Because US 10,442,846 does not claim a specific dosage regimen or approved product label, its value is primarily platform and composition-of-matter value. The strongest revenue protection would arise from a coordinated estate covering:

• The exact clinical peptide.
• PEGylation chemistry.
• Pharmaceutical formulation.
• Manufacturing process.
• Approved indication.
• Dosing schedule.
• Device or administration system.

Key Takeaways

• US 10,442,846 claims a broad genus of cysteine-containing, optionally PEGylated hepcidin mimetics.
• The patent covers peptide compositions, pharmaceutical compositions and treatment methods for iron-overload diseases.
• Claims 4, 5, 8 and 9 provide narrower sequence-specific fallbacks.
• The patent is potentially relevant to rusfertide/PTG-300, but exact sequence mapping is required.
• The expected nominal patent term reaches into 2035, subject to USPTO patent-term adjustment and any later extension.
• The patent is not an Orange Book-listed product patent absent an approved reference drug and FDA listing.
• No established Paragraph IV challenge, ANDA litigation or settlement is identified.
• Biosimilar risk is limited because a synthetic peptide would more likely face a peptide follow-on or 505(b)(2) pathway.
• The main legal vulnerabilities are written-description, enablement, functional claim construction and the drafting defect in claim 5.
• Manufacturing complexity involving cysteine pairing and PEGylation may create a practical barrier beyond the patent claims.

FAQs About US Patent 10,442,846

Is US 10,442,846 a hepcidin patent?

Yes. Its claims cover synthetic peptides that exhibit hepcidin activity or bind ferroportin, together with compositions and methods for treating iron-metabolism diseases.

Does US 10,442,846 cover PTG-300?

It may cover PTG-300 if the commercial peptide satisfies the claimed X′ and Y′ sequence, terminal chemistry, PEGylation and disulfide limitations. A definitive answer requires comparison with the exact PTG-300 structure.

Can a competitor avoid the patent by removing PEG?

Removing PEG may avoid a PEG-specific implementation, but claim 1 makes PEGylation optional. An unPEGylated peptide can still infringe if it meets the remaining structural limitations.

Does the patent cover iron chelators?

No. The claims are directed to peptides and peptide compositions. Small-molecule iron chelators fall outside the claimed composition unless another patent applies.

Does patent expiration automatically permit generic launch?

No. Launch timing also depends on FDA approval requirements, Orange Book listings, other patent-family members, regulatory exclusivity, manufacturing readiness and any litigation or settlement restrictions.

References

1. United States Patent and Trademark Office. (2019). U.S. Patent No. 10,442,846, peptide compounds and methods of use. USPTO Patent Center.
2. Protagonist Therapeutics, Inc. (2023). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.
3. ClinicalTrials.gov. (n.d.). Study of rusfertide in participants with polycythemia vera. National Library of Medicine.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.

Drugs Protected by US Patent 10,442,846

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Takeda Pharms Am	MIMRYLO	rusfertide acetate	POWDER;SUBCUTANEOUS	220605-001	Aug 28, 2026		RX	Yes	Yes			Y	Y		TREATMENT OF ERYTHROCYTOSIS IN ADULTS WITH POLYCYTHEMIA VERA (PV)
Takeda Pharms Am	MIMRYLO	rusfertide acetate	POWDER;SUBCUTANEOUS	220605-002	Aug 28, 2026		RX	Yes	Yes			Y	Y		TREATMENT OF ERYTHROCYTOSIS IN ADULTS WITH POLYCYTHEMIA VERA (PV)
Takeda Pharms Am	MIMRYLO	rusfertide acetate	POWDER;SUBCUTANEOUS	220605-003	Aug 28, 2026		RX	Yes	Yes			Y	Y		TREATMENT OF ERYTHROCYTOSIS IN ADULTS WITH POLYCYTHEMIA VERA (PV)

International Family Members for US Patent 10,442,846

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014232954
Australia	2018260800
Canada	2906830