Details for Patent: 10,125,171

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Which drugs does patent 10,125,171 protect, and when does it expire?

Patent 10,125,171 protects SYFOVRE and EMPAVELI and is included in two NDAs.

This patent has thirty-one patent family members in twelve countries.

Summary for Patent: 10,125,171

Title:	Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof
Abstract:	In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.
Inventor(s):	Cedric Francois, Pascal Deschatelets
Assignee:	Apellis Pharmaceuticals Inc
Application Number:	US14/116,591
Patent Claim Types: see list of patent claims	Compound;

United States Patent 10,125,171: Claim Scope, Exclusivity, and Compstatin Patent Landscape

U.S. Patent No. 10,125,171 covers long-acting, multivalent compstatin analogs that combine a complement-inhibitory cyclic peptide with a clearance-reducing group. The principal commercial relevance is pegcetacoplan, the PEGylated compstatin analog used in Empaveli and Syfovre. The claims are composition claims, not claims limited to a particular disease or administration regimen.

The patent is broadest at claim 1, which covers PEG-linked compstatin analogs incorporating specified cyclic peptide sequences, terminal amino acids, oligo(ethylene glycol) spacers, amine-containing residues, and a broad list of chemical linking groups. Claim 2 expands the clearance-reducing group to include PEG, an immunoglobulin Fc domain, albumin, or an albumin-binding peptide. Dependent claims narrow the estate to lysine-containing constructs, short or defined spacers, PEG architectures, multivalent compounds, selected peptide sequences, and long plasma half-life.

What does U.S. Patent 10,125,171 protect?

The patent protects a molecular architecture with four required structural components:

1. A cyclic compstatin peptide.
2. One or more terminal amino acids attached to the peptide.
3. An oligo(ethylene glycol)-containing spacer.
4. A clearance-reducing moiety attached through an amine-bearing amino acid and a chemical linking group.

The claimed arrangement can be represented as:

cyclic compstatin peptide - oligo(ethylene glycol) spacer - amine-bearing amino acid - linker - clearance-reducing moiety

For claim 1, the clearance-reducing moiety must include PEG. Claim 2 is broader in the identity of the clearance-reducing moiety but narrower in the claimed peptide sequences, limited to SEQ ID NOs: 28, 32, or 34.

Claim architecture

Claim	Principal subject matter	Commercial relevance
1	PEGylated compstatin analogs containing SEQ ID NOs 3-36, terminal amino acids, oligo(ethylene glycol) spacers and amine-linked PEG	Broad platform claim
2	Compstatin analogs using PEG, Fc, albumin or albumin-binding peptide	Broad clearance-extension claim
3	Claim 2 with Lys as the terminal amino acid	Supports lysine-based conjugation
4	Oligo(ethylene glycol) spacer with n=1-10	Short spacer embodiments
5	Combined alkyl and oligo(ethylene glycol) spacer	Mixed hydrophobic-hydrophilic linker
6	NH2(CH2CH2O)nCH2C(O)OH or NHS ester spacer	Defined synthetic intermediate
7	AEEAc or related amino-polyether acid spacer	Specific linker chemistry
8-12	Linear, branched, multiple or bifunctional PEG groups	Covers alternative PEG geometry
13-15	Multiple compstatin units, polymeric scaffolds and PEG-linked terminal units	Multivalent and dimeric products
16-18	Selected compstatin sequences, including SEQ ID NOs 28, 32 and 34	Sequence-specific protection
19-21	Plasma half-life of at least two, three or four days in primates	Pharmacokinetic limitation

How broad is claim 1 of U.S. Patent 10,125,171?

Claim 1 is structurally broad but technically constrained. It requires every element in the claimed molecular order. A potentially infringing molecule would generally need to include:

• A cyclic peptide corresponding to one of SEQ ID NOs 3-36.
• A terminal extension at the N-terminus, C-terminus, or both.
• An amine-containing amino acid separated from the cyclic peptide by an oligo(ethylene glycol) spacer.
• PEG covalently connected to the amine-containing amino acid.
• A linker falling within one of the enumerated chemical categories.

The linker list is extensive. It includes unsaturated alkyl groups, nonaromatic cyclic systems, aromatic moieties, ethers, amides, esters, carbonyls, imines, thioethers and amino acid residues. This creates substantial coverage around common conjugation chemistries.

The claim does not require:

• A particular disease indication.
• A particular dose.
• A particular route of administration.
• A particular commercial formulation.
• A particular PEG molecular weight.
• A particular terminal amino acid, except where narrower claims apply.
• A particular peptide sequence within the broader SEQ ID NOs 3-36 list.

The main limitations are sequence identity, cyclic structure, spacer placement and the requirement that the clearance-reducing group be attached through the specified amine-bearing extension.

What does claim 2 add to the patent scope?

Claim 2 changes the coverage in two ways.

First, it narrows the cyclic peptide to SEQ ID NOs 28, 32 or 34. Second, it expands the clearance-reducing moiety beyond PEG to include:

• The Fc domain of an immunoglobulin.
• Albumin.
• An albumin-binding peptide.
• PEG.

This claim is important because it covers alternative half-life-extension strategies that could be used to avoid a PEG-only limitation. A developer using an Fc-fusion, albumin-linked construct or albumin-binding peptide would still face claim 2 if the remaining structural limitations were satisfied.

The claim does not require PEG when an Fc, albumin or albumin-binding peptide is used. That distinction increases the potential relevance of claim 2 to non-PEG follow-on products.

What formulations are protected by U.S. Patent 10,125,171?

The patent claims molecular compositions rather than finished dosage-form formulations. The claims do not expressly recite:

• A buffer.
• A pH range.
• An isotonicity agent.
• A preservative.
• A concentration.
• A vial, prefilled syringe or autoinjector.
• A freeze-dried formulation.
• A specific storage condition.

The patent can therefore read on an active pharmaceutical ingredient incorporated into different formulations, but it is not, based on the claims provided, a conventional formulation patent.

This distinction matters for pegcetacoplan. A commercial product can face separate patent protection for the active conjugate, manufacturing process, formulation, delivery device or method of use. A formulation change would not necessarily avoid a composition claim if the same claimed conjugate remains present.

How do claims 3 through 15 affect infringement risk?

Claims 3-15 provide narrower fallback positions and protect common development choices.

Lysine conjugation

Claim 3 requires Lys as the terminal amino acid. Lysine is a practical conjugation handle because its side-chain primary amine supports amide, urea, carbamate and related bond formation. A product using a different amine-bearing amino acid may avoid claim 3 but could remain within claim 1 or claim 2.

Spacer chemistry

Claims 4-7 protect short oligo(ethylene glycol) spacers and defined amino-polyether intermediates. Claim 7 identifies AEEAc and 11-amino-3,6,9-trioxaundecanoic acid or their NHS esters.

These claims create a risk for products using standard amino-PEG-acid or NHS-activated PEG reagents. A developer that changes the spacer length may avoid claims 4 or 7 while remaining within the broader range of claim 1 or claim 2, which allows n from 1 to 500.

PEG topology

Claims 8-12 cover:

• Linear PEG.
• Branched PEG.
• Multiple PEG groups.
• Modified PEG groups.
• Bifunctional PEG.

Claim 15 covers a construct with a compstatin analog at each end of a linear PEG. This is a dimeric architecture and is distinct from a mono-PEGylated product.

Multivalent products

Claims 13 and 14 cover multiple compstatin analog moieties and polymeric or scaffold-linked constructs. These claims could apply to dendritic, polymeric, backbone-linked or other multivalent complement inhibitors.

A multivalent product may face greater claim exposure than a monovalent product because it can satisfy both the multiple-moiety claims and the underlying spacer and linker limitations.

What sequences are most important under the patent?

Claims 16-18 focus on selected sequence embodiments:

• SEQ ID NOs 28, 32 and 34.
• An N-methylglycine residue at the position corresponding to position 8 of SEQ ID NO:8.
• SEQ ID NO:28 specifically.

The sequence limitations are important because compstatin analog potency often depends on substitutions that improve complement C3 binding, proteolytic stability or pharmacokinetics. A molecule outside the listed sequence scope may avoid literal infringement, although the doctrine of equivalents could remain relevant depending on the substituted residue and claim construction.

The N-methylglycine limitation is particularly significant. N-methylation can affect conformation, protease resistance and receptor binding. A product lacking that modification may avoid claim 17 but could still fall within claims 1, 2, 16 or 18 if its overall sequence and conjugation architecture satisfy those claims.

What is the importance of claims 19 through 21?

Claims 19-21 introduce pharmacokinetic limitations:

• At least two days of plasma half-life in a primate.
• At least three days.
• At least four days.

These claims are narrower than the structural claims because infringement depends on both molecular structure and measured pharmacokinetic performance.

A competitor may challenge these claims on multiple grounds:

• The product does not meet the minimum half-life.
• The primate study does not use intravenous administration.
• The study does not establish the claimed half-life with adequate statistical support.
• The accused molecule has a different structure and does not satisfy the underlying composition limitations.
• The claim is indefinite if the measurement protocol is not adequately defined, depending on the intrinsic record.

The half-life claims may have commercial value because long systemic exposure is central to the differentiation of pegcetacoplan from shorter-acting complement inhibitors.

How does the patent relate to pegcetacoplan?

Pegcetacoplan is a PEGylated synthetic cyclic peptide that inhibits complement component C3. It is marketed as Empaveli for paroxysmal nocturnal hemoglobinuria and as Syfovre for geographic atrophy secondary to age-related macular degeneration [1, 2].

The claimed architecture is highly relevant to pegcetacoplan because the product uses:

• A compstatin-derived cyclic peptide.
• PEG-based clearance reduction.
• A covalent conjugation strategy.
• Long systemic exposure.
• Complement C3 inhibition.

The claims provided do not establish, by themselves, that every commercial pegcetacoplan molecule falls within every claim. That determination requires comparison of the marketed product's exact sequence, stereochemistry, linker, PEG architecture, attachment position and manufacturing specification against the patent's prosecution history and claim construction record.

What is the FDA regulatory status of products relevant to this patent?

Product	Active ingredient	FDA pathway	Approval	Indication
Empaveli	Pegcetacoplan	Biologics license application	May 14, 2021	Paroxysmal nocturnal hemoglobinuria
Syfovre	Pegcetacoplan	Biologics license application	February 17, 2023	Geographic atrophy secondary to AMD

Empaveli received orphan-drug designation for paroxysmal nocturnal hemoglobinuria. Syfovre was approved for geographic atrophy, a large ophthalmic market with repeated dosing and substantial commercial exposure.

Because pegcetacoplan is regulated as a biologic, the relevant abbreviated competition pathway is generally a biosimilar application under section 351(k), not an ANDA under the Hatch-Waxman framework. The Orange Book is therefore not the principal source for pegcetacoplan patent information. The Purple Book and the biologics patent-exchange process are more relevant [3, 4].

When does pegcetacoplan lose exclusivity?

Regulatory and patent exclusivity must be separated.

Regulatory exclusivity

Empaveli's orphan exclusivity is generally measured from its approval date and is directed to the approved orphan indication. Syfovre has biologic reference-product exclusivity measured from its first licensure date under the Public Health Service Act.

Regulatory exclusivity does not necessarily prevent all competing products. It may be indication-specific, product-specific or subject to statutory exceptions.

Patent exclusivity

The expiration date for U.S. Patent 10,125,171 cannot be determined from the claims alone. The controlling date depends on:

• The earliest effective nonprovisional priority date.
• Patent-term adjustment.
• Any terminal disclaimer.
• Patent-term extension or other statutory adjustment.
• Continuation and divisional relationships.
• Corrected patent data maintained by the USPTO.

The patent's effective commercial life must therefore be analyzed at the family level rather than by reading the grant number alone. A freedom-to-operate review should include related continuations, divisionals and patents covering pegcetacoplan sequence, composition, formulation, manufacturing and use.

Are Paragraph IV challenges relevant?

A Paragraph IV certification is an ANDA mechanism for small-molecule drugs. It is not the standard route for a biosimilar to pegcetacoplan.

For a competing pegcetacoplan product, the relevant risk is a section 351(k) biosimilar application and the Biologics Price Competition and Innovation Act patent-exchange process. A biosimilar sponsor may seek approval for the same reference product while contesting patent validity, enforceability or infringement.

For a non-biologic small-molecule compstatin analog, an ANDA may not be appropriate if the product's active ingredient is a complex peptide or biologic. The regulatory classification would depend on FDA's treatment of the specific product.

Which companies are challenging the pegcetacoplan estate?

The principal commercial competition has come from other complement inhibitors rather than from a publicly established generic or biosimilar launch against pegcetacoplan.

Relevant competing products include:

Product	Company	Target	Administration profile
Empaveli/Syfovre	Apellis Pharmaceuticals	C3	Systemic or intravitreal, depending on product
Iptacopan	Novartis	Factor B	Oral factor B inhibition
Danicopan	Alexion/AstraZeneca	Factor D	Oral factor D inhibition
Ravulizumab	Alexion/AstraZeneca	C5	Long-acting anti-C5 antibody
Pegcetacoplan alternatives in development	Multiple developers	C3 or upstream complement targets	Product-specific

These products compete clinically without necessarily infringing the claims of Patent 10,125,171. A rival that uses an antibody, small molecule or unrelated peptide scaffold may avoid the compstatin composition claims entirely.

How strong is the patent estate?

The estate is strongest against products that reproduce the full conjugation concept:

• A listed compstatin cyclic sequence.
• An oligo(ethylene glycol) spacer.
• An amine-bearing terminal amino acid.
• A PEG or other clearance-reducing moiety.
• A covered chemical linker.
• A monovalent or multivalent architecture within the claim language.

The estate is weaker against:

• Non-compstatin complement inhibitors.
• Small-molecule C3 inhibitors.
• Antibodies and antibody fragments.
• Compstatin analogs with materially different sequences.
• Constructs using unrelated half-life technologies.
• Products that remove the claimed oligo(ethylene glycol) spacer.
• Products with a different attachment topology that falls outside the required molecular order.

Validity pressure is most likely to focus on written description, enablement, obviousness, anticipation by earlier compstatin and PEGylation disclosures, and the breadth of the sequence and linker genus. The patent's detailed dependent claims improve fallback positions if the broadest composition claims are narrowed.

What manufacturing and IP barriers remain?

The patent does not necessarily capture every manufacturing step needed to produce a commercial pegcetacoplan product. Separate barriers may include:

• Solid-phase peptide synthesis.
• Cyclization and disulfide formation.
• Site-specific PEGylation.
• Purification of mono- and multi-PEG species.
• Control of PEG molecular-weight distribution.
• Removal of positional isomers and aggregates.
• Analytical characterization of the conjugate.
• Sterile manufacturing and release testing.

A competitor may design around the composition claims yet face process patents, trade secrets, analytical comparability requirements and regulatory delay. For biologics, manufacturing comparability can be a practical barrier even when a patent challenge succeeds.

What patent litigation and settlement issues should be monitored?

The key litigation questions are:

1. Whether Patent 10,125,171 is listed or otherwise identified in the biologics patent exchange for pegcetacoplan.
2. Whether related continuation patents remain in force after the expiration of this patent.
3. Whether a biosimilar applicant makes a patent notice or initiates a declaratory judgment action.
4. Whether Apellis asserts composition, method-of-use, formulation or manufacturing patents.
5. Whether any settlement includes a licensed entry date, restricted indication or supply arrangement.
6. Whether the FDA grants interchangeable status or only biosimilar status to a competing product.

Publicly reported commercial competition does not establish a Paragraph IV proceeding because that mechanism is not the ordinary pathway for pegcetacoplan.

What is the revenue exposure?

Pegcetacoplan has exposure in two commercially distinct markets:

• Hematology, through Empaveli.
• Ophthalmology, through Syfovre.

The ophthalmic market is potentially larger because geographic atrophy affects a substantial Medicare-age population and treatment can require repeated intravitreal administration. Patent exposure therefore extends beyond the current revenue base to the future duration and frequency of Syfovre use.

A successful design-around or biosimilar could affect pricing, contracting, payer access and treatment penetration before complete patent expiry if regulatory exclusivity has ended and the competing product avoids enforceable claims.

Key Takeaways

• U.S. Patent 10,125,171 is a composition patent directed to long-acting compstatin analogs.
• Claim 1 focuses on PEGylated constructs with listed cyclic peptide sequences, oligo(ethylene glycol) spacers, amine-bearing terminal amino acids and covered linkers.
• Claim 2 adds Fc, albumin and albumin-binding peptide clearance technologies while narrowing the peptide sequences.
• Claims 3-15 protect lysine conjugation, specific spacers, PEG topology and multivalent architectures.
• Claims 19-21 protect constructs with at least two, three or four days of primate plasma half-life.
• The claims are relevant to pegcetacoplan but do not, without a product-sequence and prosecution-history comparison, establish infringement by Empaveli or Syfovre.
• Pegcetacoplan competition is governed primarily by the biologics framework, not an Orange Book Paragraph IV pathway.
• A complete exclusivity analysis must review related patent-family members, terminal disclaimers, patent-term adjustment, formulation patents, method-of-use patents and manufacturing patents.

FAQs

Is U.S. Patent 10,125,171 an Orange Book patent?

No. Pegcetacoplan is regulated as a biologic, so the Purple Book and BPCIA patent-exchange framework are more relevant than the Orange Book.

Does the patent cover all PEGylated complement inhibitors?

No. It is limited to compstatin-derived cyclic peptide structures and the claimed spacer, amine, linker and clearance-reducing architecture.

Can an Fc-fusion compstatin analog infringe this patent?

Yes, potentially. Claim 2 expressly includes an immunoglobulin Fc domain as a clearance-reducing moiety, provided the remaining sequence, spacer and linker limitations are met.

Does changing the PEG molecular weight avoid the patent?

Not necessarily. The claims provided do not impose a single PEG molecular weight. Changing PEG size may avoid a narrower claim or create a noninfringement argument, but it does not automatically avoid the broader composition claims.

Are competing C3 inhibitors likely to infringe Patent 10,125,171?

Usually not if they use a non-compstatin scaffold, such as a small molecule or antibody. Infringement depends on the accused product's complete molecular structure, not merely its C3 mechanism.

References

1. U.S. Food and Drug Administration. (2021). Empaveli (pegcetacoplan) prescribing information.
2. U.S. Food and Drug Administration. (2023). Syfovre (pegcetacoplan) prescribing information.
3. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.
4. U.S. Patent and Trademark Office. (2018). United States Patent No. 10,125,171.

Drugs Protected by US Patent 10,125,171

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Apellis Pharms	SYFOVRE	pegcetacoplan	SOLUTION;INTRAVITREAL	217171-001	Feb 17, 2023		RX	Yes	Yes	10,125,171			Y
Apellis Pharms	EMPAVELI	pegcetacoplan	SOLUTION;SUBCUTANEOUS	215014-001	May 14, 2021		RX	Yes	Yes	10,125,171			Y

Foreign Priority and PCT Information for Patent: 10,125,171

PCT Information
PCT Filed	May 11, 2012	PCT Application Number:	PCT/US2012/037648
PCT Publication Date:	November 15, 2012	PCT Publication Number:	WO2012/155107

International Family Members for US Patent 10,125,171

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2012253294
Australia	2017245334
Australia	2019226186
Brazil	112013028816