# US 11,112,402 B2 · Reagents and methods for detecting PNH type II white blood cells and their identification as risk factors for thrombotic disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,112,402 B2 - Document ID: US11112402B2 - Status: Granted - Kind: B2 - Application number: 16/155,528 - Filed: 2018-10-09 - Published: 2019-01-24 - Granted: 2021-09-07 - Earliest claimed: 2009-11-09 - Assignees: Alexion Pharmaceuticals, Inc. - Applicants: Alexion Pharmaceuticals, Inc. - Inventors: Mayur Movalia; Andrea Illingworth; Susan Faas McKnight; Russell P. Rother - Web page: https://patentgrep.com/patent/US11112402B2 ## CPC - G01N 33/5094: {for blood cell populations (red blood cells G01N33/80)} - A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids - A61K 31/727: Heparin; Heparan - A61K 35/19: Platelets; Megacaryocytes - A61K 38/196: {Thrombopoietin} - A61K 38/4886: {Metalloendopeptidases (3.4.24), e.g. collagenase} - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - C07K 16/40: against enzymes - G01N 33/56972: {White blood cells} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 2800/226: Thrombotic disorders, i.e. thrombo-embolism irrespective of location/organ involved, e.g. renal vein thrombosis, venous thrombosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The disclosure relates to methods for detecting PNH Type II cell populations in biological samples as well as methods for determining whether a patient is at an increased risk for developing thrombocytopenia or thrombosis based on the percentage of PNH Type II cells in the patient's blood. The disclosure also features reagents and conjugates for use in the methods. ## Claims ### Claim 1 A method for treating a patient, the method comprising administering to a patient in need thereof one or both of an anti-thrombotic therapy and an anti-thrombocytopenic therapy, wherein the patient has been determined to have a paroxysmal nocturnal hemoglobinuria (PNH) Type II white blood cell population that is between 1.2% and 65.3%, inclusive of 1.2% and 65.3%, of the patient's total granulocytes. ### Claim 2 (depends on 1) The method of claim 1, wherein the anti-thrombotic therapy is an anticoagulant. ### Claim 3 (depends on 1) The method claim 1, wherein the anti-thrombocytopenic therapy is a platelet transfusion. ### Claim 4 (depends on 1) The method of claim 1, wherein a non-lytic variant form of aerolysin protein is used to determine the percentage of PNH Type II white blood cells. ### Claim 5 (depends on 2) The method of claim 2, wherein the anticoagulant is coumadin, heparin, or derivatives thereof. ### Claim 6 (depends on 1) The method claim 1, wherein the anti-thrombocytopenic therapy is a corticosteroid. ### Claim 7 (depends on 1) The method claim 1, wherein the anti-thrombocytopenic therapy is a splenectomy. ### Claim 8 (depends on 1) The method claim 1, wherein the anti-thrombocytopenic therapy is a platelet production-stimulating agent. ### Claim 9 (depends on 8) The method of claim 8, wherein the platelet production-stimulating agent is thrombopoietin (TPO) or a thrombopoietin mimetic. ### Claim 10 (depends on 2) The method of claim 2, wherein the anticoagulant is coumadin. ### Claim 11 (depends on 2) The method of claim 2, wherein the anticoagulant is heparin. ### Claim 12 (depends on 1) The method of claim 1, wherein the anti-thrombotic therapy is a thrombolytic agent. ### Claim 13 (depends on 12) The method of claim 12, wherein the thrombolytic agent is a tissue plasminogen activator. ### Claim 14 (depends on 12) The method of claim 12, wherein the thrombolytic agent is streptokinase. ### Claim 15 (depends on 12) The method of claim 12, wherein the thrombolytic agent is a urokinase-type plasminogen activator. ### Claim 16 (depends on 1) The method of claim 1, comprising administering to the patient a complement inhibitor. ### Claim 17 (depends on 16) The method of claim 16, comprising administering to the patient an anti-C5 antibody. ### Claim 18 (depends on 17) The method of claim 17, comprising administering to the patient eculizumab. ### Claim 19 A method for treating a patient, the method comprising administering to a patient in need thereof eculizumab and one or both of an anti-thrombotic therapy and an anti-thrombocytopenic therapy, wherein the patient has been determined to have a paroxysmal nocturnal hemoglobinuria (PNH) Type II white blood cell population that is between 1.2% and 65.3%, inclusive of 1.2% and 65.3%, of the patient's total granulocytes.