DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATMENT OF ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS) IN PEDIATRIC PATIENTS
AssigneeAlexion Pharmaceuticals, Inc.
InventorsLori PAYTON, Andrew DENKER, Eugene Scott SWENSON, Rajendra PRADHAN, Stephan ORTIZ, Marc VALLEE, Christian MIX, Xiang GAO
Life of this patent
Estimating the term…
Abstract
Provided are methods for clinical treatment of Atypical Hemolytic Uremic Syndrome (aHUS) using an anti-C5 antibody, or antigen binding fragment thereof, in pediatric patients.
Claims27
A method of treating a human pediatric patient with Atypical Hemolytic Uremic Syndrome (aHUS), the method comprising administering to the patient 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 thereof, is administered:
- (a) once on Day 1 at a loading dose of:
- i. 600 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 900 mg to a patient weighing ≥20 to <30 kg,
- iv. 1200 mg to a patient weighing ≥30 to <40 kg,
- v. 2400 mg to a patient weighing ≥40 to <60 kg,
- vi. 2700 mg to a patient weighing ≥60 to <100 kg, or
- vii. 3000 mg to a patient weighing ≥100 kg;
- and
- (b) on Day 15 at a maintenance dose of:
- i. 300 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 2100 mg to a patient weighing ≥20 to <30 kg,
- iv. 2700 mg to a patient weighing ≥30 to <40 kg,
- v. 3000 mg to a patient weighing ≥40 to <60 kg,
- vi. 3300 mg to a patient weighing ≥60 to <100 kg, or
- vii. 3600 mg to a patient weighing ≥100 kg;
- wherein patients weighing <20 kg receive additional maintenance doses every four weeks thereafter, and patients weighing ≥20 kg receive additional maintenance doses every eight weeks thereafter.
A method of treating a human pediatric patient with Atypical Hemolytic Uremic Syndrome (aHUS), the method comprising administering to the patient 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, CDR1, CDR2 and CDR3 light chain sequences as set forth in SEQ ID NOs:4, 5 and 6, respectively, and a variant human Fc constant region that binds to human neonatal Fc receptor (FcRn), wherein the variant human Fc CH3 constant region comprises Met429Leu and Asn435Ser substitutions at residues corresponding to methionine 428 and asparagine 434, each according to the EU numbering convention, wherein the anti-C5 antibody or antigen binding fragment thereof, is administered:
- (a) once on Day 1 at a loading dose of:
- i. 600 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 900 mg to a patient weighing ≥20 to <30 kg,
- iv. 1200 mg to a patient weighing ≥30 to <40 kg,
- v. 2400 mg to a patient weighing ≥40 to <60 kg,
- vi. 2700 mg to a patient weighing ≥60 to <100 kg, or
- vii. 3000 mg to a patient weighing ≥100 kg;
- and
- (b) on Day 15 at a maintenance dose of:
- i. 300 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 2100 mg to a patient weighing ≥20 to <30 kg,
- iv. 2700 mg to a patient weighing ≥30 to <40 kg,
- v. 3000 mg to a patient weighing ≥40 to <60 kg,
- vi. 3300 mg to a patient weighing >60 to <100 kg, or
- vii. 3600 mg to a patient weighing ≥100 kg;
- wherein patients weighing <20 kg receive additional maintenance doses every four weeks thereafter, and patients weighing ≥20 kg receive additional maintenance doses every eight weeks thereafter.
4-5. (canceled)
16-17. (canceled)
(canceled)
(canceled)
25-33. (canceled)
A kit for treating Atypical Hemolytic Uremic Syndrome (aHUS) in a human pediatric patient, the kit comprising:
- (a) a dose of an anti-C5 antibody or antigen binding fragment thereof, comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:12, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:8;
- and
- (b) instructions for using the anti-C5 antibody or antigen binding fragment thereof in the
35-41. (canceled)
An anti-C5 antibody or antigen binding fragment thereof comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:12, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:8, wherein the anti-C5 antibody or antigen binding fragment thereof is administered:
- (a) once on Day 1 at a loading dose of:
- i. 600 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 900 mg to a patient weighing ≥20 to <30 kg,
- iv. 1200 mg to a patient weighing ≥30 to <40 kg,
- v. 2400 mg to a patient weighing ≥40 to <60 kg,
- vi. 2700 mg to a patient weighing ≥60 to <100 kg, or
- vii. 3000 mg to a patient weighing ≥100 kg;
- and
- (b) on Day 15 at a maintenance dose of:
- i. 300 mg to a patient weighing ≥5 to <10 kg,
- ii. 600 mg to a patient weighing ≥10 to <20 kg,
- iii. 2100 mg to a patient weighing ≥20 to <30 kg,
- iv. 2700 mg to a patient weighing ≥30 to <40 kg,
- v. 3000 mg to a patient weighing ≥40 to <60 kg,
- vi. 3300 mg to a patient weighing ≥60 to <100 kg, or
- vii. 3600 mg to a patient weighing ≥100 kg;
- wherein patients weighing <20 kg receive additional maintenance doses every four weeks thereafter, and patients weighing ≥20 kg receive additional maintenance doses every eight weeks thereafter.
(canceled)
Dependencies are inferred from the claim text.