Novel genes and proteins that home to developing microvessels

Abstract

Described herein are polypeptides that home to developing microvasculature, (also referred to as developing microvessels), such as newly developing microvasculature in mammals, particularly in humans, and to DNA that encodes such polypeptides. These polypeptides are referred to herein as developing microvasculature homing polypeptides. In a specific embodiment, the homing peptides are collateral vessel endothelia (CVE) homing polypeptides, which have been shown to home to collateral vessel endothelia after ischemia.

1 . A developing vessel homing polypeptide that homes to a developing vessel. 
     
     
         2 . The homing polypeptide of  claim 1 , wherein the developing vessel is a developing microvessel or developing collateral vessel. 
     
     
         3 . The homing polypeptide of  claim 1  attached to a biodegradable delivery agent. 
     
     
         4 . The homing polypeptide of  claim 1  encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6; SEQ ID NO: 7; SEQ ID NO: 8; SEQ ID NO: 9; SEQ ID NO: 10; SEQ ID NO: 11; SEQ ID NO: 12; SEQ ID NO: 13 and a sequence that, due to the degeneracy of the genetic code, encodes the same polypeptide as a polypeptide encoded by any one of SEQ ID NOs.: 1-13. 
     
     
         5 . The homing polypeptide of  claim 1  comprising an amino acid sequence of selected from the group consisting of: SEQ ID NO: 14; SEQ ID NO: 15; SEQ ID NO: 16; SEQ ID NO: 17; SEQ ID NO: 18; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 21; SEQ ID NO: 22; SEQ ID NO: 23 and a fragment thereof. 
     
     
         6 . The homing polypeptide of  claim 1  that homes specifically to developing microvasculature in vulnerable plaque. 
     
     
         7 . The homing polypeptide of  claim 1  that homes specifically to developing microvasculature in the retina. 
     
     
         8 . The homing polypeptide of  claim 1  that homes specifically to developing microvasculature associated with a cancerous tumor or non-cancerous tumor. 
     
     
         9 . The homing polypeptide of  claim 1  that homes specifically to a developing collateral blood vessel. 
     
     
         10 . A polynucleotide encoding a homing polypeptide wherein the polynucleotide is selected from the group consisting of: SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6; SEQ ID NO: 7; SEQ ID NO: 8; SEQ ID NO: 9; SEQ ID NO 10; SEQ ID NO 11; SEQ ID NO: 12; SEQ ID NO: 13 and a sequence that, due to the degeneracy of the genetic code, encodes the same polypeptide as a polypeptide encoded by any one of SEQ ID NOs.: 1-13, complements thereof and nucleic acids that hybridize under stringent conditions to the polynucleotides. 
     
     
         11 . An antibody, or a fragment thereof, that specifically binds the developing microvasculature homing polypeptide of  claim 1 . 
     
     
         12 . An antibody, or a fragment thereof, that specifically binds a developing microvasculature homing polypeptide selected from the group consisting of: SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23; or encoded by a polynucleotide selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 and a sequence that, due to the degeneracy of the genetic code, encodes the same polypeptide as a polypeptide encoded by any one of SEQ ID NOs.: 1-13. 
     
     
         13 . (canceled) 
     
     
         14 . The antibody of  claim 11 , wherein the antibody is a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a bispecific antibody, a heteroconjugate antibody, or a single chain (ScFv) antibody. 
     
     
         15 . The antibody of  claim 14 , wherein the antibody is coupled to a therapeutic moiety. 
     
     
         16 . The antibody of  claim 15 , wherein the therapeutic moiety is selected from the group consisting of ricin, a radioisotope, a clotting agent, a thrombolytic factor, a chemotherapeutic agent, a radiosensitizing agent, an anti-angiogenesis agent, an anti-motility agent and an immunomodulatory agent. 
     
     
         17 . The antibody of  claim 14 , wherein the antibody is coupled to a radiologic or other imaging molecule. 
     
     
         18 . The antibody of  claim 17 , wherein the radiologic or other imaging molecule is selected from the group consisting of a radioisotope, a dye, a pigment and a fluorescent molecule. 
     
     
         19 - 24 . (canceled) 
     
     
         25 . The homing polypeptide of  claim 1  coupled to a therapeutic moiety. 
     
     
         26 - 28 . (canceled) 
     
     
         29 . A method of targeting an agent to developing microvasculature in an individual, comprising administering to an individual in need thereof an effective amount of a composition comprising the homing polypeptide of  claim 1  and an agent to be targeted to developing microvasculature, whereby the agent is targeted to developing microvasculature. 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 29 , wherein the developing microvasculature is associated with vulnerable plaque, age related macular degeneration (AMD), tumors, or newly developing blood vessels. 
     
     
         32 - 47 . (canceled)