Methods and systems for treating eclampsia or pre-eclampsia
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 receptor (sFlt-1) antibody bound to a solid support in order to reduce blood levels of sFlt-1. Further disclosed are the sequences of the heavy chain and light chain CDRs of the anti-sFlt-1 antibodies.
1. An anti-sFlt-1 antibody which comprises heavy chain CDRs having the amino acid sequence SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22 and light chain CDRs having the amino acid sequence SEQ ID NO:24, SEQ ID NO:26, and SEQ ID NO:28.
2. The anti-sFlt-1 antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence SEQ ID NO:30 or a sequence at least 85% identical thereto and the light chain comprises the amino acid sequence SEQ ID NO:32 or a sequence at least 85% identical thereto.
3. The anti-sFlt-1 antibody of claim 1 , wherein the anti-sFlt-1 antibody binds to one or more of domains 1-3 of sFlt-1.
4. The anti-sFlt-1 antibody of claim 1 , wherein the anti-sFlt-1 antibody does not block ligand binding to sFlt-1.
5. A method of treating eclampsia or pre-eclampsia in a subject comprising providing ex vivo to the subject an anti-sFlt-1 antibody, or sFlt-1 binding fragment thereof, which comprises the anti-sFlt-1 antibody of claim 1 .
6. The method of claim 5 , wherein the heavy chain comprises the amino acid sequence SEQ ID NO:30 or a sequence at least 85% identical thereto and the light chain comprises the amino acid sequence SEQ ID NO:32 or a sequence at least 85% identical thereto.
7. The method of claim 5 , wherein the anti-sFlt-1 antibody binds to one or more of domains 1-3 of sFlt-1.
8. The method of claim 5 , wherein the anti-sFlt-1 antibody does not block ligand binding to sFlt-1.
9. The method of claim 5 , wherein the pregnancy-related hypertensive disorder is pre-eclampsia.
10. The method of claim 9 , wherein the subject is a pregnant human or a post-partum human.
11. The method of claim 10 , wherein, the subject is a pregnant human.
12. The method of claim 5 , which comprises:
(a) removing blood from the subject,
(b) passing the blood or a component thereof over a solid support to which are attached anti-sFlt-1 antibodies, or sFlt-1 binding fragments thereof, to decrease the level of sFlt-1 in the blood or component thereof, and
(c) returning the blood or component thereof to the subject's body.
13. The method of claim 12 , 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 solid support.
14. A system comprising:
(a) anti-sFlt-1 antibodies, wherein the anti-sFlt-1 antibodies comprise the anti-sFlt-1 antibodies of claim 1 , or sFlt-1 binding fragments thereof;
(b) first means for conveying blood or a component thereof from a subject to the anti-sFlt-1 antibodies, or sFlt-1 binding fragments thereof, bound to the solid support so as to contact the blood or a component thereof with the anti-sFlt-1 antibodies, or sFlt-1 binding fragments thereof, and thereby remove sFlt-1 from the blood or a component thereof; and
(c) 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-sFlt-1 antibodies, or sFlt-1 binding fragments thereof.
15. An anti-sFlt-1 antibody or sFlt-1 binding fragment thereof, which competes for binding with an antibody which comprises heavy chain CDRs having the amino acid sequence SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22 and light chain CDRs having the amino acid sequence SEQ ID NO:24, SEQ ID NO:26, and SEQ ID NO:28.
16. The anti-sFlt-1 antibody or sFlt-1 binding fragment of claim 15 , wherein the anti-sFlt-1 antibody, or sFlt-1 binding fragment thereof, competes for binding to sFlt-1 with an antibody which comprises a heavy chain.
17. A method of treating eclampsia or pre-eclampsia in a subject comprising providing ex vivo to the subject an anti-sFlt-1 antibody, or sFlt-1 binding fragment thereof which competes for binding with the anti-sFlt-1 antibody or sFlt-1 binding fragment thereof of claim 15 .
18. The method of claim 17 , wherein the anti-sFlt-1 antibody, or sFlt-1 binding fragment thereof, competes for binding to sFlt-1 with an antibody which comprises the amino acid sequence SEQ ID NO:30.
19. The method of claim 17 , wherein the anti-sFlt-1 antibody, or sFlt-1 binding fragment thereof, competes for binding to sFlt-1 with an antibody which comprising a heavy chain having the amino acid sequence SEQ ID NO:30 and a light chain having the amino acid sequence SEQ ID NO:32.