Modified DDAH polypeptides and their use to extracorporeally treat a patient's blood to reduce levels of ADMA
AssigneeThe Trustees of Indiana University
InventorJaipal Singh
Life of this patent
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Abstract
Modified DDAH polypeptides and their uses thereof are provided. Exemplary embodiments provide DDAH polypeptides which include one or more amino acid substitutions, additions, or deletions with natural or non-naturally encoded amino acids, and/or linkage to other biologically active molecules including other DDAH polypeptides, as well as PKEM. Additionally, use of said DDAH polypeptides for treatment of disease, such as heart failure or renal disease, is also provided.
Claims14
A system comprising a DDAH polypeptide for extracorporeally treating a patient's blood and reducing ADMA levels in said blood, said system comprising
- a DDAH polypeptide and
- a solid support, wherein said DDAH polypeptide is covalently linked to said solid support;
- and
- a device configured to receive a patient's blood and return the blood to the patient's circulation after contact with said solid support, wherein said device comprises said solid support in a configuration that places said solid support in fluid communication with blood that passes through the device, wherein said blood has reduced ADMA levels after contacting the solid support relative to the ADMA levels in the blood prior to contact with the solid support.
A system comprising a DDAH polypeptide for extracorporeally treating a patient's blood and reducing ADMA levels in said blood, said system comprising
- a solid support;
- two or more different DDAH polypeptides covalently linked to said solid support, wherein the two or more different DDAH polypeptides comprise amino acid sequences independently selected from amino acid sequences having at least 95% sequence identity to SEQ ID NO:
- 1;
- SEQ ID NO:
- 2;
- SEQ ID NO:
- 5;
- SEQ ID NO:
- 6;
- SEQ ID NO:
- 7;
- SEQ ID NO:
- 9;
- SEQ ID NO:
- 10;
- SEQ ID NO:
- 11;
- SEQ ID NO:
- 12;
- or SEQ ID NO:
- 13;
- and
- a device configured to receive a patient's blood and return the blood to the patient's circulation after contact with said solid support, wherein said device comprises said solid support in a configuration that places said solid support in fluid communication with blood that passes through the device, wherein said blood has reduced ADMA levels after contacting the solid support relative to the ADMA levels in the blood prior to contact with the solid support.
A system comprising a DDAH polypeptide for extracorporeally treating a patient's blood, said system comprising
- a DDAH polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17;
- a solid support, wherein said DDAH polypeptide is covalently linked to said solid support;
- and
- a device configured to receive a patient's blood and return the treated blood to the patient's circulation, wherein said device comprises said solid support in a configuration that places said solid support in fluid communication with blood that passes through the device.
A method of reducing levels of ADMA in a patient's blood, said method comprising the steps of
- removing blood from said patient;
- contacting the patient's blood with a DDAH polypeptide;
- and
- returning the blood to the patient's circulation after the blood has been contacted by said DDAH polypeptide, wherein the returned blood has a lower ADMA concentration than the blood originally taken from the patient.
Dependencies are inferred from the claim text.