Details for Patent: 9,056,076

Which drugs does patent 9,056,076 protect, and when does it expire?

Patent 9,056,076 protects SYFOVRE and is included in one NDA.

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

Summary for Patent: 9,056,076

Title:	Method of treating age-related macular degeneration comprising administering a compstatin analog
Abstract:	The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and/or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.
Inventor(s):	Pascal Deschatelets, Paul Olson, Cedric Francois
Assignee:	Apellis Pharmaceuticals Inc
Application Number:	US13/409,941
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 9,056,076: Scope, Claim Analysis, Expiration and Compstatin Patent Landscape

US Patent 9,056,076 is a method-of-treatment patent directed to using compstatin analogs to treat age-related macular degeneration. Its broadest claim covers administering an effective amount of any qualifying compstatin analog to a patient with ARMD. Dependent claims narrow the invention by peptide structure, cyclization pattern, non-standard amino acids, C3 inhibitory activity, intravitreal delivery and local ocular administration.

The patent is commercially relevant to pegcetacoplan, marketed as Syfovre by Apellis Pharmaceuticals for geographic atrophy secondary to AMD. The patent’s principal weaknesses are its method-of-use format, the breadth of the structural definitions, and the need to prove that a commercial peptide falls within the claimed compstatin-analog genus. Its principal strength is the combination of a broad ARMD treatment claim with specific claims directed to cyclic C3 inhibitors and ocular administration.

What does US Patent 9,056,076 protect?

US 9,056,076 protects methods of treating ARMD by administering a composition containing a compstatin analog. The patent does not, based on the claims supplied, independently claim:

• A particular commercial peptide composition;
• Pegcetacoplan as a named molecule;
• A PEGylation architecture;
• A specific dosage or concentration;
• A manufacturing process;
• A formulation excipient system;
• A dosing interval; or
• A pharmaceutical composition standing alone.

Claim 1 is the broadest independent claim:

A method of treating ARMD comprising administering a composition comprising an effective amount of a compstatin analog.

The claim has four core limitations:

Limitation	Scope
Disease	Age-related macular degeneration
Product administered	A composition
Active ingredient	A compstatin analog
Therapeutic act	Administration of an effective amount

The claim does not expressly require intravitreal injection. Claims 11 and 19 add intravitreal and local ocular administration, respectively.

How broad is claim 1?

Claim 1 is broad at the level of therapeutic use but depends on the meaning of “compstatin analog.” The term is narrowed by the dependent claims and the patent specification, which identify cyclic peptides related to the compstatin scaffold and compounds that inhibit complement component C3.

A generic or biosimilar applicant could challenge claim 1 on several grounds:

1. The administered molecule is not a compstatin analog as properly construed.
2. The product is not administered for ARMD.
3. The treatment does not use an effective amount.
4. The claim lacks written description or enablement across the full analog genus.
5. The asserted analog was anticipated or rendered obvious by earlier compstatin disclosures.
6. The patent’s disclosure does not adequately support all ARMD subtypes or all claimed analog structures.

The claim is stronger against a product specifically designed as a C3 inhibitor based on the compstatin scaffold. It is weaker against an unrelated complement inhibitor, such as a C5 inhibitor, because the product would not ordinarily fall within the compstatin-analog limitation.

What peptide structures are covered by claims 2 through 10?

Claims 2 through 10 define progressively narrower cyclic-peptide classes.

Core sequence requirements

Claims 2 and 3 require a core sequence containing:

• Trp or a Trp analog;
• Gln;
• Asp;
• A second Trp or Trp analog; and
• Gly.

Claim 3 adds a sixth residue selected from His, Ala, certain methylated unbranched amino acids, Phe, Trp or Trp analogs.

These limitations target the pharmacophore associated with compstatin’s C3-binding activity. They do not restrict the claims to native compstatin. Substitution with non-standard amino acids is expressly contemplated.

Compstatin-derived sequence architecture

Claim 4 covers a longer peptide in which multiple residues remain identical to corresponding residues in compstatin. Claim 5 covers a related 13-residue architecture with cyclization between positions corresponding to the second and twelfth residues.

Claim 5 contains an apparent sequence-identification inconsistency because it refers to SEQ ID NO: 5 while claim 4 also uses SEQ ID NO: 5. The operative scope would likely depend on the specification, prosecution history and whether the inconsistency is treated as a correctable clerical error or an ambiguity affecting claim construction.

Specific cyclic peptide class

Claim 6 is the most commercially important structural claim. It covers a peptide with the following general pattern:

Ile/Val/Leu or related N-terminal group - Cys - Val - Trp analog - Gln - Asp - Trp analog - Gly-related residue - His/Ala/Phe/Trp-related residue - His - Arg - Cys - C-terminal residue

The two cysteines are joined by a disulfide bond. The claim permits:

• N-terminal blocking groups;
• C-terminal amidation or other blocking groups;
• Trp analogs with increased hydrophobicity;
• Bicyclic or multiple monocyclic aromatic structures;
• D- or L-amino acids; and
• Short terminal extensions.

Claims 7 and 8 cover acetylation at the N-terminus and amidation at the C-terminus. Claim 9 covers more hydrophobic Trp analogs. Claim 10 covers aromatic substitutions, including bicyclic aromatic systems.

These claims are directed toward improving potency, stability, binding and pharmacokinetic properties while preserving the compstatin binding mode.

Does US 9,056,076 cover pegcetacoplan or Syfovre?

The patent presents a credible basis for asserting coverage against a compstatin-derived ophthalmic C3 inhibitor, including a peptide corresponding to the structural class described in claim 6. Pegcetacoplan is a PEGylated compstatin analog that inhibits C3 and is administered by intravitreal injection for geographic atrophy secondary to AMD. Syfovre received FDA approval in February 2023.[2]

The infringement analysis would turn on the actual molecular structure, including:

• The sequence of the cyclic peptide;
• The position and identity of any non-standard amino acid;
• N-terminal and C-terminal modifications;
• The disulfide linkage;
• The location and chemistry of PEG attachment;
• Whether the PEG moiety is part of the claimed “composition” or affects the claimed analog identity; and
• The product label’s ARMD indication and administration route.

Claim group	Potential relevance to pegcetacoplan
Claim 1	Broad treatment claim for ARMD using a compstatin analog
Claims 2-5	Potential coverage depending on sequence and cyclic architecture
Claims 6-8	Most relevant structural claims for a modified cyclic compstatin analog
Claims 9-10	Relevant if the molecule contains the specified hydrophobic or aromatic Trp analog
Claims 11 and 19	Relevant to intravitreal or local ocular administration
Claims 12-17	Potentially relevant to 11-residue cyclic portions, substitutions and non-standard amino acids
Claim 18	Relevant if the product binds the same C3 region and has at least 10-fold compstatin activity

A patent claim chart against pegcetacoplan would require the marketed molecule’s exact sequence and linker disclosure. The claims supplied do not establish literal infringement by themselves.

What is the significance of claim 18’s 10-fold activity limitation?

Claim 18 requires the analog to:

1. Bind substantially the same region of human C3 as compstatin; and
2. Have C3 inhibitory activity at least 10 times greater than compstatin.

This is a functional limitation. It could substantially narrow the claim in litigation because the patent holder would need to establish both binding-site similarity and relative potency.

The relevant assay conditions would matter. A tenfold potency comparison can vary with:

• The C3 assay format;
• Species and protein source;
• Complement activation pathway;
• Peptide concentration;
• Endpoint selection;
• PEGylation state;
• Serum conditions; and
• The comparator version of compstatin.

Claim 18 is stronger as a commercial-screening limitation than as a simple structural limitation. It may capture high-potency next-generation analogs that differ materially in sequence but retain the same C3 mechanism.

What are the patent expiration and exclusivity dates?

The patent’s priority and filing history determine the effective patent term. Based on the patent record, the relevant patent term is tied to a 2007 nonprovisional filing and is expected to run into late 2027, subject to any patent-term adjustment, terminal disclaimer or other term calculation shown in the USPTO maintenance and patent-term records.[1]

Protection type	Relevant date or period
US 9,056,076 patent term	Expected to end in late 2027, subject to USPTO term calculation
Syfovre FDA approval	February 17, 2023
Reference-product biologic exclusivity	Potentially through February 2035 under the 12-year biologics framework
Patent-based protection	Potentially earlier than regulatory exclusivity
Method-of-use coverage	Depends on claim scope, listed patents and product labeling

Pegcetacoplan is regulated as a complex peptide therapeutic rather than a conventional small-molecule generic product. FDA approval of Syfovre does not by itself establish the duration of all patent or regulatory protections. A follow-on applicant would need to assess the Purple Book pathway, FDA exclusivity, patent listings and the Biologics Price Competition and Innovation Act procedures.[3]

What is the Orange Book status of US 9,056,076?

The Orange Book is principally relevant to approved drug products submitted under an NDA. Biologic reference-product and biosimilar issues are generally analyzed through the Purple Book and the BPCIA framework. Syfovre’s regulatory classification and any associated patent listings must be reviewed in the FDA’s current product and patent databases.

US 9,056,076 is a method-of-treatment patent. Even if listed for an approved product, its practical impact would depend on:

• Whether the patent is listed against Syfovre;
• The listed use code;
• Whether the approved label includes the claimed ARMD use;
• Whether a follow-on applicant can carve out the patented indication;
• Whether the patent is expired or disclaimed; and
• Whether the applicant proceeds under an NDA or a 351(k) biosimilar application.

For a 351(k) applicant, the key patent-risk mechanism is the BPCIA patent-exchange process rather than a conventional Hatch-Waxman Paragraph IV notice alone.

Are Paragraph IV challenges relevant?

A Paragraph IV challenge is principally associated with ANDA filings for small-molecule drugs. A 351(k) biosimilar applicant generally uses the BPCIA patent dance and related declaratory-judgment procedures.

A Paragraph IV strategy could become relevant only if the FDA product and application pathway support an ANDA or another NDA-based generic route. For pegcetacoplan, the more likely competitive pathway is biosimilar or interchangeable-biologic development, subject to FDA classification and product-specific requirements.

A competitor could still pursue a patent-invalidity or noninfringement position based on:

• Lack of written description for the full peptide genus;
• Lack of enablement;
• Anticipation by earlier compstatin analog publications;
• Obviousness based on known C3 inhibitors;
• Indefiniteness of “substantially the same region”;
• Indefiniteness of “effective amount” in the relevant context; or
• Failure to meet the 10-fold activity threshold in claim 18.

What biosimilar and generic entry risks exist?

Biosimilar risk

The principal long-term threat to Syfovre is a follow-on biologic or complex-peptide product that can demonstrate sufficient similarity while avoiding unexpired patent claims. A biosimilar applicant may attempt to:

• Use a different PEG attachment point;
• Modify the linker;
• Change the dosing schedule;
• Seek a narrower label;
• Omit geographic atrophy if that indication is patent-protected;
• Challenge the patent’s written description; or
• Rely on a non-compstatin complement inhibitor.

A biosimilar that retains the compstatin scaffold and intravitreal ARMD use faces greater risk under claims 1, 6, 11 and 19.

Generic risk

Traditional generic substitution is less likely than biosimilar competition because pegcetacoplan is a complex, PEGylated cyclic peptide. Analytical characterization, immunogenicity, comparability and clinical bridging create manufacturing and regulatory barriers even after patent expiry.

Which competing drugs have different patent risks?

The most relevant competitive comparator is avacincaptad pegol, marketed as Izervay by Iveric Bio, an Astellas company. Izervay is a C5 inhibitor approved for geographic atrophy secondary to AMD.[4]

Product	Target	Modality	Relevance to US 9,056,076
Syfovre, pegcetacoplan	C3	PEGylated compstatin analog	Directly relevant
Izervay, avacincaptad pegol	C5	Complement inhibitor	Generally outside compstatin-analog claims
Beovu, aflibercept and other anti-VEGF products	VEGF pathway	Recombinant biologics	Outside the claimed C3 peptide genus
Investigational C3 inhibitors	C3	Various molecules	Risk depends on compstatin relationship

US 9,056,076 is unlikely to block an unrelated C5 inhibitor or anti-VEGF product. It can, however, create freedom-to-operate risk for companies developing a compstatin-derived C3 inhibitor for retinal disease.

What licensing deals and ownership issues matter?

The compstatin technology has been associated with research originating at the University of Pennsylvania and commercial development by Apellis and its predecessor or affiliated entities. The commercial analysis should distinguish:

• Ownership of the underlying compstatin discovery;
• Exclusive licenses covering analogs or therapeutic uses;
• Improvements relating to PEGylation;
• Separate patents covering manufacturing and formulation;
• Patent assignments recorded at the USPTO; and
• Royalty or milestone obligations in license agreements.

US 9,056,076 should not be treated as the entire commercial estate. A product such as Syfovre may depend on several patent families covering the active peptide, PEGylation, conjugation chemistry, formulations, dosing, administration and therapeutic indications.

What is the litigation and settlement status?

The supplied claims do not identify litigation, settlements or license disputes involving US 9,056,076. The patent’s litigation exposure must be separated into two categories:

1. Direct enforcement against a compstatin-derived ARMD product; and
2. Invalidity or noninfringement challenges in connection with biosimilar entry.

The absence of a litigation allegation in the claim text does not establish freedom from dispute. For transaction or launch analysis, the relevant records are USPTO assignment and maintenance data, FDA patent listings, federal district court dockets, BPCIA notices and any license or settlement terms disclosed by the patent owner or product sponsor.

How strong is the patent estate for US 9,056,076?

The patent has moderate-to-strong blocking value against the specific combination of:

• A compstatin-derived C3 inhibitor;
• ARMD treatment;
• Ocular or intravitreal administration; and
• A peptide containing the claimed cyclic and modified-residue architecture.

Its blocking value is lower against:

• Non-compstatin C3 inhibitors;
• C5 inhibitors;
• Anti-VEGF products;
• Systemic complement therapies;
• Products labeled for non-ARMD indications; and
• Products launched after the patent term but during any remaining regulatory exclusivity.

The strongest claims for commercial enforcement are likely claims 1, 6, 11 and 19. Claims 9, 10 and 18 may provide more technical specificity but impose greater proof requirements. Claims 12 through 17 broaden the analog concept through identity and substitution language but may face greater validity scrutiny for written description and enablement.

Key Takeaways

• US 9,056,076 is a method-of-treatment patent, not a standalone composition or manufacturing patent.
• Claim 1 broadly targets administration of a compstatin analog for ARMD.
• Claims 6 through 10 are the most important structural claims for a modified cyclic compstatin peptide.
• Claims 11 and 19 cover intravitreal and local ocular administration.
• Claim 18 requires the analog to bind the same C3 region and show at least 10-fold greater inhibitory activity than compstatin.
• The patent is expected to expire in late 2027, subject to the USPTO’s final term calculation.
• Syfovre’s potential biologic exclusivity may extend beyond the patent term, potentially into 2035.
• Pegcetacoplan presents the clearest potential commercial overlap.
• Izervay, anti-VEGF products and unrelated complement inhibitors generally present lower risk under these claims.
• Biosimilar entry is more relevant than conventional generic entry.
• The full commercial patent estate likely includes separate families covering peptide composition, PEGylation, formulations, manufacturing and dosing.

FAQs

Can US 9,056,076 block a C5 inhibitor for geographic atrophy?

Generally no. The claims require a compstatin analog, which is a C3-directed peptide class. A C5 inhibitor such as avacincaptad pegol would normally fall outside that structural limitation.

Does intravitreal injection alone infringe US 9,056,076?

No. Intravitreal administration satisfies only an administration-route limitation. The product must also be a compstatin analog, and the treatment must be directed to ARMD under the applicable claim.

Can a company avoid the patent by changing the PEG attachment site?

Possibly, but not automatically. A change in PEG attachment may avoid a composition or conjugation claim while still infringing a method claim if the resulting compound remains a claimed compstatin analog and is used to treat ARMD.

Is a peptide with 50% sequence identity automatically covered?

No. Claim 12 also requires a cyclic portion 11 amino acids in length and the other structural limitations stated in the claim. Sequence identity alone is insufficient.

Can a biosimilar launch after patent expiration without waiting for 2035?

Patent expiration and biologic exclusivity are separate barriers. A biosimilar may remain subject to FDA reference-product exclusivity, patent litigation, regulatory requirements and any other unexpired patent families after US 9,056,076 expires.

References

1. United States Patent and Trademark Office. (2015). U.S. Patent No. 9,056,076, compstatin analogs for treatment of age-related macular degeneration.
2. U.S. Food and Drug Administration. (2023, February 17). FDA approves treatment for geographic atrophy secondary to age-related macular degeneration.
3. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.
4. U.S. Food and Drug Administration. (2023, August 4). FDA approves new treatment for geographic atrophy secondary to age-related macular degeneration.

Drugs Protected by US Patent 9,056,076

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	9,056,076					TREATMENT OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION BY INTRAVITREAL ADMINISTRATION OF PEGCETACOPLAN

International Family Members for US Patent 9,056,076

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006302212
Australia	2007207385
Australia	2013203946
Australia	2016253654