# US 12,599,323 B2 · Methods and systems for treating pregnancy-related hypertensive disorders comprising anti-sEng and anti-sFlt-1 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,323 B2 - Document ID: US12599323B2 - Status: Granted - Kind: B2 - Application number: 17/783,801 - Filed: 2020-12-08 - Published: 2023-02-23 - Granted: 2026-04-14 - Earliest claimed: 2019-12-13 - Assignees: Aggamin LLC - Applicants: Aggamin, LLC - Inventors: Woo S. Joo; Karen M. Lee; Adelene Y. Tan; Garrett D. Daniels; Paul Kussie - Web page: https://patentgrep.com/patent/US12599323B2 ## CPC - A61B 5/15: Devices for taking samples of blood - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - A61P 9/12: Antihypertensives - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere} - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/526: CH3 domain - C07K 2317/71: Decreased effector function due to an Fc-modification - C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors" - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract Disclosed are methods and apparatuses for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using ex vivo treatment with an anti-sFlt-1 antibody and an anti-sEng antibody bound to a solid support in order to reduce blood levels of sFlt-1 and sEng. The present disclosure relates to methods, systems, devices, and apparatuses for treating pregnancy-related hypertensive disorders such as pre-eclampsia and eclampsia. ## Claims ### Claim 1 A method of treating a pregnancy-related hypertensive disorder in a subject in need thereof, the method comprising providing ex vivo to the subject an anti-soluble Endoglin (sEng) antibody or sEng-binding fragment thereof and an anti-soluble fms-like tyrosine kinase 1 (sFlt-1) antibody or sFlt-1-binding fragment thereof, wherein the anti-sEng antibody or sEng-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprises a CDR1, CDR2, and CDR3, and wherein: the sequence of CDR1H comprises SEQ ID NO:7; the sequence of CDR2H comprises SEQ ID NO:8; the sequence of CDR3H comprises SEQ ID NO:9; the sequence of CDR1L comprises SEQ ID NO:10; the sequence of CDR2L comprises SEQ ID NO:11; the sequence of CDR3L comprises SEQ ID NO:12; and wherein the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprises a CDR1, CDR2, and CDR3, and wherein: the sequence of CDR1H comprises SEQ ID NO:1; the sequence of CDR2H comprises SEQ ID NO:2; the sequence of CDR3H comprises SEQ ID NO:3; the sequence of CDR1L comprises SEQ ID NO:4; the sequence of CDR2L comprises SEQ ID NO:5; and the sequence of CDR3L comprises SEQ ID NO:6. ### Claim 2 (depends on 1) The method of claim 1, wherein: (a) the heavy chain variable region of the anti-sEng antibody or sEng-binding fragment thereof comprises a sequence at least 85% identical to SEQ ID NO:22, wherein the light chain variable region of the anti-sEng antibody or sEng-binding fragment thereof comprises a sequence at least 85% identical to SEQ ID NO:24; and (b) the heavy chain variable region of the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof comprises a sequence at least 85% identical to SEQ ID NO:14, and wherein the light chain variable region of the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof comprises a sequence at least 85% identical to SEQ ID NO:16. ### Claim 3 (depends on 1) The method of claim 1, wherein: (a) the heavy chain variable region of the anti-sEng antibody or sEng-binding fragment thereof comprises SEQ ID NO:22, wherein the light chain variable region of the anti-sEng antibody or sEng-binding fragment thereof comprises SEQ ID NO:24; and (b) the heavy chain variable region of the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof comprises SEQ ID NO: 14, and wherein the light chain variable region of the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof comprises SEQ ID NO:16. ### Claim 4 (depends on 1) The method of claim 1, wherein: (a) the anti-sEng antibody or sEng-binding fragment thereof has a heavy chain comprising a sequence at least 85% identical to SEQ ID NO:26, wherein the anti-sEng antibody or sEng-binding fragment thereof has a light chain comprising a sequence at least 85% identical to SEQ ID NO:28; and (b) the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof has a heavy chain comprising a sequence at least 85% identical to SEQ ID NO:18 and wherein the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof has a light chain comprising a sequence at least 85% identical to SEQ ID NO: 20. ### Claim 5 (depends on 1) The method of claim 1, wherein: (a) the anti-sEng antibody or sEng-binding fragment thereof has a heavy chain comprising SEQ ID NO: 26, wherein the anti-sEng antibody or sEng-binding fragment thereof has a light chain comprising SEQ ID NO:28; and (b) the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof has a heavy chain comprising SEQ ID NO: 18 and wherein the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof has a light chain comprising SEQ ID NO:20. ### Claim 6 (depends on 1) The method of claim 1, wherein the pregnancy-related hypertensive disorder is eclampsia, pre-eclampsia, or HELLP syndrome. ### Claim 7 (depends on 6) The method of claim 6, wherein the pregnancy-related hypertensive disorder is pre-eclampsia. ### Claim 8 (depends on 6) The method of claim 6, wherein the pregnancy-related hypertensive disorder is HELLP syndrome. ### Claim 9 (depends on 1) The method of claim 1, wherein the subject is a pregnant human or a postpartum human. ### Claim 10 (depends on 9) The method of claim 9, wherein, the subject is a pregnant human. ### Claim 11 (depends on 1) The method of claim 1, wherein the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to one or more solid supports. ### Claim 12 (depends on 11) The method of claim 11, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to the same solid support. ### Claim 13 (depends on 11) The method of claim 11, wherein the support-bound sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to different solid supports. ### Claim 14 (depends on 1) The method of claim 1, the method comprising: (a) removing blood from the subject, (b) passing the blood or a component thereof over one or more solid supports to which are bound anti-sEng antibodies or sEng-binding fragments thereof and anti-sFlt-1 antibodies or sFlt-1-binding fragments thereof, to decrease the levels of sEng and sFlt-1 in the blood or component thereof, and (c) returning the blood or component thereof to the subject's body. ### Claim 15 (depends on 14) The method of claim 14, wherein the blood or a component thereof comprises plasma and the method comprises removing a volume of the subject's blood and separating the blood into plasma and cellular components and passing the plasma over the one or more solid supports. ### Claim 16 (depends on 14) The method of claim 14, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are provided in a single column. ### Claim 17 (depends on 14) The method of claim 14, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof is provided in a first column and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof is provided in a second column. ### Claim 18 (depends on 1) An immunoadsorption device comprising: (a) the anti-sEng antibody or sEng-binding fragment thereof of claim 1 and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof of claim 1, wherein the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to one or more solid supports; (b) a first means for conveying blood or a component thereof from a subject to the anti-sEng antibody or sEng-binding fragment thereof and anti-sFlt-1 antibody or sFlt-1-binding fragment thereof bound to the one or more solid supports so as to contact the blood or a component thereof with the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof and thereby to remove sEng and sFlt-1 from the blood or a component thereof, wherein the first means comprises: (i) an access device, inserted into a blood vessel of the subject, for accessing the subject's blood system; and (ii) a conduit system, which fluidly connects the access device to the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof, bound to the one or solid supports, thereby allowing the subject's blood or a component thereof to flow to and contact the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof; and a second means for conveying the blood or a component thereof to the subject following contact of the blood or a component thereof with the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof, wherein the second means comprises: (i) a conduit system; and (ii) a return device, where the return device is inserted into a blood vessel of the subject, and where the conduit system fluidly connects the blood or a component thereof in contact with the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof, to the return device so as to allow for the return of the blood or a component thereof to the subject. ### Claim 19 (depends on 18) The immunoadsorption device of claim 18, wherein the first means comprises a device for separating the subject's blood into plasma and cellular components. ### Claim 20 (depends on 19) The immunoadsorption device of claim 19, wherein the device for separating the subject's blood into plasma and cellular components is a centrifuge or an apheresis device. ### Claim 21 (depends on 18) The immunoadsorption device of claim 18, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to the same solid support. ### Claim 22 (depends on 18) The immunoadsorption device of claim 18, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to different solid supports. ### Claim 23 (depends on 1) A column comprising: (a) the anti-sEng antibody or sEng-binding fragment thereof of claim 1; and (b) the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof of claim 1; wherein the anti-sEng antibody or sEng-binding fragment thereof and the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to a solid support. ### Claim 24 (depends on 23) The column of claim 23, wherein the support-bound anti-sEng antibody or sEng-binding fragment thereof and the support-bound anti-sFlt-1 antibody or sFlt-1-binding fragment thereof are bound to the same solid support. ### Claim 25 (depends on 1) A combination comprising: (a) a first column comprising the anti-sEng antibody or sEng-binding fragment thereof of claim 1; and (b) a second column comprising the anti-sFlt-1 antibody or sFlt-1-binding fragment thereof of claim 1.