Subcutaneous dosage and administration of anti-C5 antibodies for treatment of paroxysmal nocturnal hemoglobinuria (PNH)
Inventors
Volles, Lori • Pradhan, Rajendra • Sheridan, Douglas L. • VALLEE, Marc • Gao, Xiang
Assignees
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Publication Number
US-12240893-B2
Publication Date
2025-03-04
Expiration Date
Abstract
Provided are methods for clinical treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) comprising administering to the patient an anti-C5 antibody, or antigen binding fragment thereof, wherein the anti-C5 antibody, or antigen binding fragment thereof, is administered (or is for administration) subcutaneously according to a particular clinical dosage regimen (i.e., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the patient has previously been treated with eculizumab (Soliris®).
Core Innovation
The disclosure relates to subcutaneous treatment regimens for Paroxysmal Nocturnal Hemoglobinuria (PNH) using an anti-C5 antibody, including ravulizumab (Ultomiris; ALXN1210; BNJ441). The method administers an effective amount of an anti-C5 antibody, or antigen binding fragment thereof, during an administration cycle with an initial Day 1 intravenous dose followed by Day 15 subcutaneous dosing and every week thereafter.
The anti-C5 antibody is defined by specified heavy chain and light chain CDR1, CDR2, and CDR3 sequences provided by SEQ ID NOs. One form further specifies a variant human Fc constant region that binds to human neonatal Fc receptor (FcRn), with Met-429-Leu and Asn-435-Ser substitutions in the Fc CH3 region.
The disclosure further defines clinical and safety/effectiveness evaluation components including hemolysis markers such as LDH, breakthrough hemolysis, stabilized hemoglobin, transfusion avoidance, and major adverse vascular events (MAVEs). Outcomes and patient-reported measures include improvements assessed using FACIT-Fatigue and EORTC QLQ-C30, and satisfaction and immunogenicity endpoints include anti-ravulizumab ADAs.
Claims Coverage
The independent claims define two core treatment methods for PNH using an anti-C5 antibody specified by heavy- and light-chain CDR sequence identifiers, with defined administration timing and dosing across an administration cycle. The inventive features include the molecular identity constraints for the antibody and the specific Day 1 intravenous plus Day 15 weekly subcutaneous dosing scheme.
CDR-defined anti-C5 antibody treatment with Day 1 IV and weekly Day 15 SC dosing
Treating a human patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) by administering during an administration cycle an effective amount of an anti-C5 antibody, or antigen binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs: 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs: 4, 5, and 6, respectively, wherein the anti-C5 antibody (or antigen binding fragment) is administered intravenously on Day 1 and subcutaneously on Day 15 and every week thereafter.
FcRn-binding variant Fc anti-C5 antibody treatment with Day 1 IV and weekly Day 15 SC dosing
Treating a human patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) by administering during an administration cycle an effective amount of an anti-C5 antibody, or antigen binding fragment thereof, comprising the same CDR-defined sequences and a variant human Fc constant region that binds to human neonatal Fc receptor (FcRn), wherein the variant human Fc CH3 constant region comprises Met-429-Leu and Asn-435-Ser substitutions.
Across the independent claims, treatment of PNH relies on an anti-C5 antibody defined by specific heavy- and light-chain CDR sequence identifiers, administered during an administration cycle with an initial Day 1 intravenous dose and subsequent Day 15 subcutaneous weekly dosing. One independent claim additionally requires a variant human Fc CH3 region engineered for FcRn binding with Met-429-Leu and Asn-435-Ser substitutions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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