Compositions and methods for increasing vascularization
Inventors
Rossomando, Anthony • Silvestre, Jean-Sebastien • Tamarat, Radia
Assignees
Institut National de la Sante et de la Recherche Medicale INSERM • Sinfonia Biotherapeutics AB
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Publication Number
US-9138461-B2
Publication Date
2015-09-22
Expiration Date
Abstract
Disclosed are methods of increasing vascularization in a tissue by administering a neublastin polypeptide to a mammal exhibiting impaired or inadequate blood flow in the tissue. The methods can be used to in the treatment or prevention of a disorder characterized by impaired or inadequate blood flow or to increase vascularization in an organ that has been transplanted into a subject.
Core Innovation
The disclosure relates to Neublastin (also artemin/enovin) polypeptides for increasing vascularization and blood flow in mammals with impaired or inadequate blood flow. The problem addressed is impaired or inadequate blood flow leading to tissues with ischemia and/or inadequate perfusion, including ischemic tissues and transplanted organs.
A method is described that includes selecting a human exhibiting impaired or inadequate blood flow in a tissue and administering an amount of a neublastin polypeptide effective to increase vascularization in the tissue. The polypeptide comprises an amino acid sequence at least 80% identical to amino acids 15-113 of SEQ ID NO:1 and, when dimerized, binds to a complex containing GFRalpha3 and RET.
The disclosure further describes that the human has received a transplanted organ and that administration of the polypeptide increases vascularization in the transplanted organ. Additional embodiments expand neublastin sequence identity options and include administration contexts such as ischemic tissue and transplanted organ settings.
Claims Coverage
The independent claim covers a method for increasing vascularization in a tissue by selecting a human with impaired or inadequate blood flow and administering an effective amount of a neublastin polypeptide meeting a defined sequence identity requirement. The claim includes an inventive requirement that the polypeptide is dimerized and binds a complex containing GFRalpha3 and RET, with vascularization increased in a transplanted organ after administration.
Dimerized neublastin polypeptide binds a GFRalpha3/RET complex
Administering to the human an amount of a polypeptide effective to increase vascularization in the tissue, wherein the polypeptide comprises an amino acid sequence at least 80% identical to amino acids 15-113 of SEQ ID NO:1 and, when dimerized, binds to a complex containing GFRalpha3 and RET.
Selection of human with impaired or inadequate blood flow
Selecting a human exhibiting impaired or inadequate blood flow in a tissue.
Increased vascularization in a transplanted organ
The human has received a transplanted organ and administration of the polypeptide increases vascularization in the transplanted organ.
Overall, the claim scope centers on using a dimerized neublastin polypeptide with a specified sequence identity requirement that binds a GFRalpha3/RET complex to increase vascularization, including in transplanted organs, in a human selected for impaired or inadequate blood flow.
Stated Advantages
Increasing vascularization in a tissue.
Increasing vascularization in a transplanted organ after administration.
Documented Applications
Treating or addressing tissues with impaired or inadequate blood flow by increasing vascularization, including ischemic tissues.
Increasing vascularization in transplanted organs.
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