United States Patent 9,107,861: Claim Forensics and US Landscape on Anti-C5 FcRn-Bound Complement Inhibition

US Patent 9,107,861 is directed to treating C5-mediated complement-associated diseases by administering an anti-human C5 antibody (or antigen-binding fragment) that inhibits cleavage of C5 into C5a and C5b, coupled with (1) a very specific binding/epitope and pH-dependent binding requirement defined by CDR sequences and Kd ratios, and (2) a very specific neonatal Fc receptor (FcRn) binding Fc variant defined by CH3 substitutions (Met-429-Leu and Asn-435-Ser in EU numbering) plus a serum half-life threshold. The claims are narrow in the sense that they require a defined set of CDR sequences and a defined Fc variant; they also broaden in the sense that they cover multiple C5-mediated indications (including PNH and aHUS) and multiple antibody formats (antibody or antigen-binding fragment), but the core novelty is tied to the particular CDR set plus Fc engineering and pH-shifted binding behavior.

What do the independent claim limitations actually require?

Independent claim 1 (and the functionally parallel claim 11, 16 variants) is a bundle of hard constraints. An accused product or method must satisfy all required features simultaneously:

Core mechanism and target

Treats a patient with a “C5 mediated complement-associated condition.”
Administers an antibody (or antigen-binding fragment) that:
- Binds human C5
- Inhibits cleavage of C5 into C5a and C5b

CDR sequence constraints (binding specificity is fixed)

The antibody must comprise:

Heavy chain CDR1 = amino acid sequence in SEQ ID NO:23
Heavy chain CDR2 = amino acid sequence in SEQ ID NO:19
Heavy chain CDR3 = amino acid sequence in SEQ ID NO:3
Light chain CDR1 = amino acid sequence in SEQ ID NO:4
Light chain CDR2 = amino acid sequence in SEQ ID NO:5
Light chain CDR3 = amino acid sequence in SEQ ID NO:6

This is a classic “define by sequences” claim approach. It is not “binds C5” in a functional sense only; it requires the CDRs to match the listed sequences.

Fc engineering constraints (FcRn engagement is fixed)

The antibody must include:

A variant human IgG Fc constant region that binds human FcRn
CH3 domain includes:
- Met-429-Leu and Asn-435-Ser at residues corresponding to methionine 428 and asparagine 434 of native IgG Fc, in EU numbering

So, FcRn binding is not just implied by “increased half-life.” The claim requires specific CH3 substitutions.

Serum half-life threshold

Claim 1 requires the antibody to have human serum half-life of at least 25 days

pH-dependent affinity constraints (subset claims introduce explicit Kd ratio)

Claims 6 to 8 specify affinity windows, and claim 8 adds a Kd ratio requirement. Not every claim version repeats all of these, but the set of claims in the bundle creates a tight claim space.

How does the claim set map to the antibody’s binding and pH behavior?

The claim text introduces three binding/affinity constructs:

Absolute Kd at pH 7.4 (neutral)

Claim 6:
Kd at pH 7.4, 25°C in range 0.1 nM ≤ Kd ≤ 1 nM

Absolute Kd at pH 6.0 (acidic, endosomal)

Claim 7:
Kd at pH 6.0, 25°C is ≥ 10 nM

Kd ratio (selectivity for pH-dependent disengagement)

Claim 8:
(Kd at pH 6.0) / (Kd at pH 7.4) > 25

Different threshold in the parallel method claim

Claim 11:
ratio > 24 (very close to claim 8; the bundle still tightens the same functional objective)

Practical reading: the claim set is designed to require C5 binding that is substantially stronger at pH 7.4 than at pH 6.0, implying pH-dependent behavior consistent with antibody engagement/disengagement in physiological compartments.

Which indications are covered, and how broad is that coverage?

The claims explicitly list two C5-mediated conditions:

Claim 9 / Claim 14 / Claim 17: Paroxysmal nocturnal hemoglobinuria (PNH)
Claim 10 / Claim 15 / Claim 18: Atypical hemolytic uremic syndrome (aHUS)

No other diseases appear in the claim excerpt you provided. The landscape impact is that any design-around still must either:

avoid meeting the molecular constraints, or
avoid the claimed indications if practicing in a jurisdiction where claim scope is limited by indication.

What is the “novelty spine” across the independent claim versions?

Independent claim 1 is the archetype; claim 11 and claim 16 are alternate structural restatements:

Claim 1

Requires:
- CDR sequence set (SEQ ID NOs)
- Fc CH3 substitutions (Met-429-Leu and Asn-435-Ser in EU)
- serum half-life ≥ 25 days
- plus the overall C5 inhibition mechanism and C5-treated method

Claim 11

Includes a more explicit Kd ratio constraint:
(Kd pH6.0)/(Kd pH7.4) > 24
Repeats:
- CDR sequences (same set)
- CH3 substitutions (same set)
- half-life ≥ 25 days
- and then states PNH or aHUS in dependent form

Claim 16

Requires only the polypeptide sequences (SEQ ID NO:14 and SEQ ID NO:11), under the same C5 inhibition method framing:
- heavy chain polypeptide = SEQ ID NO:14
- light chain polypeptide = SEQ ID NO:11
Dependent claims narrow to PNH or aHUS.

Landscape impact: claim 16 can be a fallback if an accused antibody’s CDRs map to the required heavy and light polypeptide sequences even if other dependency paths are contested.

Where do enforcement risks concentrate? (Claim elements most likely to break or survive challenges)

High-risk element for a designing competitor: fixed CDR sequences

If a competitor alters even a single residue within any of the six specified CDR sequences, they likely leave the claim scope. That creates:

low tolerance for sequence deviation
high evidentiary burden on the patent holder to prove sequence match (or equivalence where legally applicable)

High-risk element: specific Fc CH3 substitutions

Many FcRn-binding variants exist (e.g., mutations that increase FcRn affinity at acidic pH). This claim narrows to a precise pair of CH3 substitutions in EU numbering. If a competitor uses a different FcRn-binding set, the literal infringement risk drops sharply.

Medium-risk element: half-life ≥ 25 days

Half-life thresholds raise questions in litigation about measurement methods and comparability. Still, half-life is commonly measurable via PK studies in humans or validated models, and this threshold can be a strong filter against weaker Fc variants.

Medium-risk element: pH-dependent Kd windows/ratios

Kd constraints create a “test condition” problem for enforcement but also function as a precision filter. Attack routes include:

arguing measurement does not match stated conditions (pH, temperature, assay context)
challenging whether the competitor’s antibody behaves similarly across pH conditions

Mechanism constraint: inhibition of C5 cleavage

This is likely provable by functional assays and may be harder for competitors to dispute if their antibody binds C5 at all and blocks activation.

What is the competitive design space implied by these claim constraints?

A competitor trying to avoid the claim can target any one of the following:

Change one or more CDR sequences away from the listed SEQ ID NOs while maintaining C5 cleavage inhibition through a different epitope.
Use a different FcRn-binding engineering scheme than Met-429-Leu and Asn-435-Ser in CH3.
Trade off half-life, deliberately lowering PK below 25 days.
Adjust pH-dependent binding profile so that the Kd ratio at pH 6.0 vs pH 7.4 does not exceed the stated threshold (or Kd at pH 6.0 does not meet ≥10 nM, if that dependent requirement is asserted).
Use alternative Fc formats (e.g., engineered fragments lacking the claimed Fc variant) to avoid CH3 substitutions.

From a landscape perspective, elements (1) and (2) are the cleanest “literal design-around” levers.

How does this US patent likely position within the anti-C5 universe?

Anti-C5 therapy is a well-established class. This patent’s claim architecture tries to carve out incremental IP by combining:

defined C5-binding CDRs, and
a defined FcRn-binding Fc variant, and
defined pH-dependent binding behavior.

That means a typical anti-C5 antibody that lacks the exact Fc CH3 substitutions or the exact CDR set should fall outside this claim scope, even if it blocks C5 cleavage and treats PNH/aHUS.

Business implication: enforcement probability rises when the accused product uses an FcRn variant with the same CH3 substitutions and a CDR-defined epitope set consistent with the patent’s specified CDRs and Kd profile. Enforcement probability drops when competitors use alternative FcRn mutations or alternative anti-C5 binding sites.

US patent landscape: what risks does a C5 developer face around this claim?

Because the excerpt you provided contains only the claim text and not the patent’s citation network, priority chain, or prosecution history, the most actionable landscape conclusions focus on claim logic rather than named competitors.

Risk matrix for developers building anti-C5 candidates

Design choice	In-scope risk vs US 9,107,861 claim logic	Why
CDRs match the specified SEQ ID NOs (all six CDRs)	High	Claim is sequence-defined
CDRs differ in any listed CDR	Low to moderate	Likely exits literal scope
Fc includes CH3 Met-429-Leu + Asn-435-Ser (EU)	High	Specific substitution pair required
Fc uses different FcRn-binding mutations	Low	Fails literal Fc requirement
FcRn variant used, but half-life < 25 days	Moderate to low	Dependent gate
Binding affinity meets Kd range at pH 7.4 but not pH 6.0 behavior	Moderate	pH ratio constraints in dependent/parallel claims
Blocks C5 cleavage but uses different binding/pH profile	Moderate to low	Mechanism alone is insufficient

What are the critical claim “clusters” for validity challenges or prosecution history relevance?

Based on the structure, the likely contentious clusters in litigation would be:

Sequence definition scope
- Whether the listed CDRs correspond to a unique antibody identity or whether multiple variants map to the same functional binding region.
Assay-defined properties
- Kd at pH 7.4 and pH 6.0 under the stated temperature and conditions
FcRn-binding substitutions in EU numbering
- Whether competitor’s Fc is truly equivalent under EU numbering mapping
Half-life measurement
- Study design, patient demographics, formulation, and analytical methods

Those clusters translate to evidence pressure: sequence mapping, PK datasets, and binding assays.

Claim-by-claim coverage summary (from your excerpt)

Independent method claim structure

Claim 1: main method; defines CDRs, CH3 FcRn mutations, half-life ≥ 25 days; includes C5 cleavage inhibition and treatment.
Claim 11: method; repeats core CDR and Fc; adds explicit Kd ratio > 24 and half-life ≥ 25 days; then dependent claims apply indications.
Claim 16: method; recites heavy and light polypeptide sequences (SEQ ID NO:14 and SEQ ID NO:11) and requires C5 cleavage inhibition.

Dependent claim narrowing

Claims 2-4 / 12-13: further specify variable and constant regions via SEQ IDs.
Claim 5 / half-life requirement: at least 25 days.
Claims 6-8 / 11: Kd at pH and Kd ratio thresholds.
Claims 9-10 and 14-15 and 17-18: explicit indications PNH and aHUS.

Key takeaways

US 9,107,861 is not a broad “anti-C5 antibody” patent; it is a sequence-defined CDR patent coupled to a specific FcRn-binding CH3 Fc variant (Met-429-Leu and Asn-435-Ser in EU numbering) and a half-life gate (≥25 days).
The claim set also encodes pH-dependent binding behavior via Kd windows and a Kd ratio requirement (pH 6.0 vs pH 7.4).
Landscape risk for competitors concentrates on two exact-match requirements: the CDR sequences (six CDRs) and the exact CH3 Fc mutations. Differences in either are the cleanest design-around levers.
Enforcement and defense will likely hinge on evidence-heavy elements: CDR/sequence identity, assay conditions for Kd at two pH values, and PK methodology for the ≥25 day half-life threshold.

FAQs

Does the patent cover any anti-C5 antibody that inhibits C5 cleavage?
No. The claims require specific CDR sequences (SEQ ID NOs) plus a specific Fc CH3 substitutions set and a serum half-life threshold, with additional pH-dependent binding constraints in certain claims.
Is FcRn binding required for infringement?
Yes. The antibody must comprise a variant human IgG Fc constant region that binds human FcRn, with CH3 domain containing Met-429-Leu and Asn-435-Ser substitutions in EU numbering.
Are the treated indications limited?
The excerpted claim set explicitly names PNH and aHUS via dependent claims.
What is the most direct design-around strategy?
Change at least one of the six specified CDR sequences or use a different FcRn-binding Fc variant that does not include the required CH3 substitution pair.
Which claim features are most likely to drive litigation evidence?
Sequence identity of the specified CDRs, PK measurement supporting serum half-life ≥25 days, and binding assays supporting Kd values and Kd ratios across pH 7.4 and pH 6.0.

References

[1] United States Patent 9,107,861 (claims excerpt provided in prompt).

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Alexion Pharmaceuticals, Inc.	ULTOMIRIS	ravulizumab-cwvz	Injection	761108	December 21, 2018	9,107,861	2035-06-01
Alexion Pharmaceuticals, Inc.	ULTOMIRIS	ravulizumab-cwvz	Injection	761108	October 09, 2020	9,107,861	2035-06-01
Alexion Pharmaceuticals, Inc.	ULTOMIRIS	ravulizumab-cwvz	Injection	761108	June 22, 2022	9,107,861	2035-06-01
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2015134894	⤷ Start Trial
United States of America	9803007	⤷ Start Trial
United States of America	9663574	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 9,107,861

Summary for Patent: 9,107,861