US Patent 10,835,574: Claim Scope, C5-Inhibitor Patent Landscape, and Generic Entry Risk

US Patent 10,835,574 protects a C5-binding polypeptide composition, its injectable presentation, pharmacokinetic profile, hemolysis-inhibition use, and treatment of paroxysmal nocturnal hemoglobinuria (PNH). The independent claims are narrow in one respect because they require the polypeptide to contain SEQ ID NO: 1 and require sodium chloride and sodium phosphate within specified concentration ranges. The method claims are broader in commercial application but remain dependent on that composition.

The patent is potentially relevant to peptide- or protein-based C5 inhibitors administered intravenously or subcutaneously, including products developed for PNH or other complement-mediated disorders. It does not, based on the supplied claims, directly cover every anti-C5 antibody, small-molecule complement inhibitor, or unrelated C5-binding molecule.

What does US Patent 10,835,574 cover?

The patent has four principal claim groups:

Claim group	Claims	Protected subject matter
Composition	1-6	SEQ ID NO: 1 C5-binding polypeptide formulated with sodium chloride and sodium phosphate
Kit and device	7-8	Kit with instructions and auto-injector containing the claimed composition
Hemolysis treatment	9-29	Administration, dose, pharmacokinetic, efficacy, and safety limitations
PNH treatment	30-33	IV or SC treatment of PNH, including prior or unsuccessful eculizumab treatment

Claim 1 is the core composition claim. It requires:

A polypeptide comprising the amino acid sequence of SEQ ID NO: 1.
Sodium chloride at about 25 mM to about 100 mM.
Sodium phosphate at about 10 mM to about 100 mM.
A pharmaceutically acceptable excipient.

The claim does not require a particular concentration of the polypeptide, pH, administration route, indication, or device. Those limitations appear in dependent claims.

How narrow is claim 1?

Claim 1 has both sequence-specific and formulation-specific limitations.

Sequence limitation

The phrase “comprises the amino acid sequence of SEQ ID NO: 1” generally permits additional amino acids, provided the accused polypeptide still contains the recited sequence. The practical scope depends on whether SEQ ID NO: 1 is:

The complete active polypeptide;
A binding domain within a larger construct;
A sequence with terminal extensions;
A sequence containing a defined cyclization, conjugation, or post-translational modification; or
A sequence disclosed as one member of a broader C5-binding family.

A product with a materially different sequence would have a strong non-infringement position under the literal wording of claim 1. It could still face a doctrine-of-equivalents argument if the sequence changes preserve the same C5-binding function, formulation performance, and therapeutic effect, but prosecution history and claim construction would be decisive.

The supplied claims do not identify SEQ ID NO: 1. That sequence must be reviewed in the patent specification and sequence listing before making a product-specific infringement determination.

Formulation limitation

The formulation must include both sodium chloride and sodium phosphate. The claimed concentration ranges are:

Component	Claimed range
Sodium chloride	About 25 mM to about 100 mM
Sodium phosphate	About 10 mM to about 100 mM

A formulation containing the required polypeptide but using histidine, citrate, acetate, or another buffer instead of sodium phosphate would fall outside the literal scope of claim 1. A formulation using sodium chloride below 25 mM or above 100 mM could also avoid literal infringement, subject to the interpretation of “about.”

“About” creates a potential claim-construction dispute. Courts typically assess the term in light of the specification, prosecution history, analytical precision, and technical meaning. A formulation at 24 mM or 101 mM cannot automatically be classified as infringing or non-infringing.

What formulations are protected by US 10,835,574?

Claims 1-3 protect a formulation platform with optional concentration and pH limitations.

Claim	Additional limitation
1	Sodium chloride and sodium phosphate within claimed ranges
2	Polypeptide concentration of about 1-400 mg/mL
3	pH of about 6.5-7.5

Claim 2 is unusually broad in concentration. It reaches low-concentration injectable products and highly concentrated formulations intended to reduce injection volume. Claim 3 covers a near-neutral formulation range commonly used for parenteral biologics and peptides.

The patent therefore creates the greatest formulation risk where a competitor uses:

The same SEQ ID NO: 1 polypeptide;
Sodium chloride within the claimed range;
Sodium phosphate within the claimed range; and
A pH of 6.5-7.5 or a polypeptide concentration within the range of claim 2.

A design-around could use a different buffer system, a different ionic-strength strategy, or a different sequence. Such changes may affect stability, aggregation, viscosity, injection tolerability, and shelf life.

How do claims 4-6 define the C5 inhibitor?

Claims 4-6 add functional limitations to the composition.

Claim 4 requires C5 binding with a KD of about 0.1 nM to about 1 nM. This is a high-affinity range. Infringement would likely require comparative binding data, a validated assay, and a defined interpretation of equilibrium dissociation constant under the relevant test conditions.

Claim 5 requires blocking C5a production following activation of the alternative complement pathway. Claim 6 requires blocking membrane attack complex formation following activation of the classical, alternative, or lectin pathway.

These claims link the composition to a specific complement mechanism:

C5 cleavage is inhibited;
C5a generation is reduced; and
C5b-9 membrane attack complex formation is reduced.

The claims do not cover only an in vitro binding interaction. They require a measurable complement-blocking activity when the relevant pathway is activated.

What methods of use are protected?

Claims 9-29 cover treatment of hemolysis using the claimed composition. They combine therapeutic activity with pharmacokinetic and dosing limitations.

Key limitations include:

Claim	Limitation
9	Inhibiting hemolysis
10	Plasma polypeptide level of about 0.1-20 µg/mL
11	Hemolysis inhibition of about 25%-100%
12	Daily administration for at least two days
16	Subcutaneous or intravenous administration
17	Plasma half-life of at least four hours
18-19	Volume of distribution limitations
20	Clearance of about 0.04-4 mL/hr/kg
21	Tmax of about one to 48 hours
22	Measurable polypeptide substantially restricted to plasma
23	Dose of about 0.01-2 mg/kg
24	Inhibition of about 50%-99% of C5 activation
26	At least 90% hemolysis inhibition by three hours
27	Daily dose of about 0.1-60 mg/kg/day
28	Cmax of about 0.1-1,000 µg/mL
29	AUC of about 200-10,000 µg·hr/mL

The method claims are cumulative. For example, claim 26 requires the method of claim 9 and therefore incorporates claim 1 through the dependency chain. A product must use the claimed composition before the timing and efficacy limitation becomes relevant.

Does the patent cover PNH treatment?

Yes. Claim 30 specifically covers treating PNH by subcutaneous or intravenous administration of the claimed composition.

Claims 31-33 extend the PNH scope to patients previously treated with an antibody-based therapeutic, including eculizumab. Claim 32 addresses PNH that was resistant or unresponsive to that therapy.

These claims target a commercially important patient population:

Patients switching from an antibody-based C5 inhibitor;
Patients with inadequate response to eculizumab;
Patients requiring an alternative route or dosing profile; and
Patients with residual hemolysis despite prior complement inhibition.

The claims do not require a particular PNH clone size, transfusion history, lactate dehydrogenase threshold, bone marrow status, or prior treatment duration. The absence of those limitations increases the potential clinical breadth of claims 30-33, although the required composition remains a significant restriction.

What is the likely patent strength?

Strong elements

The strongest portions of the patent are likely:

The composition claim tied to an identified sequence and defined excipient system.
The formulation claims where the commercial product uses sodium chloride and sodium phosphate within the stated ranges.
The PNH method claims if the product is administered by SC or IV injection and contains the claimed polypeptide.
The auto-injector claim if the commercial presentation uses that device with the claimed formulation.

These claims can be supported with product labels, regulatory filings, batch records, formulation specifications, and analytical testing.

Vulnerable elements

The most contestable limitations are likely:

“About” the stated concentration ranges;
“Substantially restricted to the plasma compartment”;
No adverse cardiovascular, respiratory, or CNS effects for at least one month;
No changes in physiological parameters for at least one month;
Functional KD and complement inhibition results;
Pharmacokinetic ranges that may vary by species, dose, route, and assay.

Claims 13-15 are particularly dependent on clinical or nonclinical safety evidence. A claimant would need to establish that the required absence of adverse effects and physiological changes is met. A generic or biosimilar applicant could challenge whether these limitations are inherent, objectively measurable, adequately enabled, or sufficiently definite.

When does US Patent 10,835,574 lose exclusivity?

US Patent 10,835,574 issued on November 17, 2020. A US utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension under 35 U.S.C. §156 [1].

The issue date alone does not establish the expiration date. The controlling record is the USPTO patent-term calculation and the earliest effective nonprovisional filing date in the continuity chain. A complete freedom-to-operate analysis must review:

The priority applications;
Continuation and divisional relationships;
Patent-term adjustment;
Terminal disclaimer records;
Any patent-term extension;
Continuation patents with overlapping claims; and
Foreign counterparts.

The patent’s practical exclusivity period may therefore extend beyond this patent through related composition, formulation, device, manufacturing, or method-of-use patents.

What is the Orange Book status?

The Orange Book lists patents submitted by NDA holders for approved drug products, together with regulatory exclusivity information [2]. A patent number cannot be classified as an Orange Book-listed patent solely from the claim text.

If the claimed polypeptide is associated with an approved NDA, the relevant inquiry is whether US 10,835,574 was submitted for that NDA and accepted for listing. The assessment should distinguish between:

Patent listed in the Orange Book;
Patent disclosed in FDA labeling or regulatory submissions;
Patent owned or licensed by the sponsor but not listed;
Patent relevant to an unapproved investigational product; and
Patent covering a device or process rather than the approved drug substance.

If listed, a generic applicant could face a Paragraph IV certification. If not listed, the patent may still support an infringement action against commercial manufacture, use, or sale, but it would not necessarily create an Orange Book-based automatic stay.

What Paragraph IV challenges and litigation risks exist?

A Paragraph IV challenge would need to address at least four issues:

Whether the proposed product contains a polypeptide comprising SEQ ID NO: 1.
Whether the formulation contains sodium chloride and sodium phosphate within the claimed ranges.
Whether the proposed use practices the hemolysis or PNH method claims.
Whether the patent claims are invalid for anticipation, obviousness, lack of written description, lack of enablement, indefiniteness, or improper claim scope.

A formulation-only design-around may avoid claim 1 while leaving sequence or method patents in the same family intact. A sequence modification may avoid literal infringement but create regulatory comparability issues if the product is intended to be a biosimilar or follow-on biologic. A different molecular modality, such as a small-molecule factor B or factor D inhibitor, would generally present lower direct infringement risk under the supplied claims.

No litigation, settlement, or Paragraph IV outcome can be established from the supplied claim text. The patent’s litigation exposure must be evaluated against current PACER records, FDA Orange Book certifications, and related patent-family proceedings.

How does this patent compare with competing complement-inhibitor estates?

Product or class	Target	Modality	Relationship to claims 1-33
Eculizumab	C5	Monoclonal antibody	Generally outside the claimed polypeptide sequence and formulation
Ravulizumab	C5	Monoclonal antibody	Generally outside the supplied sequence-specific claims
Crovalimab	C5	Monoclonal antibody	Generally outside the supplied sequence-specific claims
Pegcetacoplan	C3	Pegylated peptide	Different complement target and sequence
Iptacopan	Factor B	Small molecule	Different target and modality
Danicopan	Factor D	Small molecule	Different target and modality
Zilucoplan-type product	C5	Peptide inhibitor	Potentially closer if the active sequence is SEQ ID NO: 1
Nomacopan-type product	C5 and LTB4	Recombinant protein	Potentially different sequence and mechanism

The principal competitive threat is a C5 inhibitor using the same sequence in a different presentation. Products using different targets, such as factor B or factor D inhibitors, may compete clinically in PNH while avoiding the direct claim elements.

What generic, biosimilar, and follow-on entry risks exist?

The entry route depends on the molecular identity of the claimed polypeptide.

Generic drug risk

A conventional ANDA pathway is more plausible for a defined synthetic peptide than for a complex recombinant protein. An ANDA applicant would face formulation, sequence, analytical, and patent-certification issues.

Biosimilar risk

If SEQ ID NO: 1 corresponds to a recombinant or engineered protein, a 351(k) biosimilar pathway may be relevant. The central patent risk would focus on sequence identity, formulation, device presentation, and clinical use. A biosimilar applicant could seek a different buffer or excipient system to avoid claim 1.

New-drug or hybrid pathway

If the product is not readily classifiable as a conventional generic or biosimilar, a 505(b)(2) or full NDA strategy could be required. That route may reduce reliance on the reference product but does not eliminate patent infringement exposure.

Key Takeaways

US Patent 10,835,574 centers on a C5-binding polypeptide containing SEQ ID NO: 1.
Claim 1 requires both sodium chloride and sodium phosphate within defined molar ranges.
Claims 2 and 3 add broad concentration and near-neutral pH limitations.
Claims 9-29 protect hemolysis treatment, dosing, pharmacokinetics, complement inhibition, and safety outcomes.
Claims 30-33 specifically target SC or IV PNH treatment, including patients previously treated with eculizumab.
The strongest infringement case would involve the same sequence, the claimed excipient system, and SC or IV treatment for hemolysis or PNH.
A different sequence or a formulation using a non-phosphate buffer may provide a design-around, subject to related patents and doctrine-of-equivalents risk.
The patent issued November 17, 2020. Its actual expiration requires review of the USPTO continuity and patent-term records.
Orange Book listing, Paragraph IV activity, litigation, and settlement status cannot be determined from the claim text alone.
Competing factor B, factor D, C3, and antibody-based C5 inhibitors generally occupy different direct claim territory.

FAQs About US Patent 10,835,574

Does US 10,835,574 cover eculizumab?

No direct coverage is apparent from the supplied claims. The claims require a polypeptide comprising SEQ ID NO: 1 and a specified sodium chloride/sodium phosphate formulation. Eculizumab is a monoclonal antibody with a different sequence and product composition.

Does the patent cover subcutaneous C5 inhibitor products?

Yes, if the product uses the claimed polypeptide composition. Claims 16, 27, and 30 expressly include subcutaneous administration.

Can a competitor avoid claim 1 by removing sodium phosphate?

Potentially. Sodium phosphate is a required element of claim 1. A formulation using a different buffer could avoid literal infringement, although related patents and equivalents analysis would remain relevant.

Are the pharmacokinetic claims independent claims?

No. Claims 17-22 and 28-29 depend through earlier claims and therefore retain the composition requirements of claim 1.

Does the patent independently protect an auto-injector?

Claim 8 covers an auto-injector comprising the pharmaceutical composition of claim 1. The device claim is therefore limited by the same sequence and excipient requirements.

Sources

United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Patent and Trademark Office. (2020). U.S. Patent No. 10,835,574. USPTO Patent Center. https://patentcenter.uspto.gov
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/generic-drug-patent-certifications-and-suitability-petitions

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ucb Inc	ZILBRYSQ	zilucoplan sodium	SOLUTION;SUBCUTANEOUS	216834-001	Oct 17, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Ucb Inc	ZILBRYSQ	zilucoplan sodium	SOLUTION;SUBCUTANEOUS	216834-002	Oct 17, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Ucb Inc	ZILBRYSQ	zilucoplan sodium	SOLUTION;SUBCUTANEOUS	216834-003	Oct 17, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	107027	⤷ Start Trial
Argentina	121381	⤷ Start Trial
Argentina	134913	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,835,574

Which drugs does patent 10,835,574 protect, and when does it expire?

Summary for Patent: 10,835,574