Modified ddah polypeptides comprising a pharmacokinetic enhancing moiety, improved pharmacology and their uses
AssigneeThe Trustees of Indiana University
InventorJaipal SINGH
Life of this patent
Estimating the term…
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.
Claims16
A method of reducing ADMA levels in a patient, said method comprising the steps of administering a modified DDAH polypeptide to a patient in need of ADMA reduction, said modified DDAH polypeptide comprising
- an amino acid sequence of SEQ ID NO:
- 1, SEQ ID NO:
- 13, SEQ ID NO:
- 15, or SEQ ID NO:
- 17, or an amino acid sequence having at least 95% sequence identity with SEQ ID NO:
- 1, SEQ ID NO:
- 13, SEQ ID NO:
- 15 or SEQ ID NO:
- 17;
- and
- a PMET covalently linked to said amino acid sequence, wherein said modified DDAH has a molecular weight of at least about 150 kDa.
A method of treating patients with elevated ADMA levels, said method comprising the steps of
- obtaining a biological sample from a patient;
- measuring ADMA levels in the biological sample to identify patients with elevated levels of ADMA;
- administering a modified DDAH polypeptide to said patients identified with elevated levels of ADMA in an amount effective to reduce ADMA levels in said patient.
Dependencies are inferred from the claim text.