Integrin Heterodimer and an Alpha Subunit Thereof

Abstract

A recombinant or isolated integrin heterodimer comprising a novel subunit α11 in association with a subunit β is described. The integrin or the subunit α11 can be used as marker or target of all types of cells. The integrin or subunit α11 thereof can be used as marker or target in different physiological or therapeutic methods. They can also be used as active ingredients in pharmaceutical compositions and vaccines.

1 - 11 . (canceled) 
     
     
         12 . An antibody or fragment thereof capable of binding specifically to integrin subunit α11, or homologues or fragments thereof, wherein the integrin subunit α11 comprises essentially the amino acid sequence shown in SEQ ID NO:2. 
     
     
         13 - 20 . (canceled) 
     
     
         21 . An antibody or fragment thereof capable of binding specifically to an integrin heterodimer comprising a subunit α11 and a subunit β, or homologues or fragments thereof, wherein the integrin subunit α11 comprises essentially the amino acid sequence shown in SEQ ID NO:2. 
     
     
         22 - 49 . (canceled) 
     
     
         50 . A method for marking or targeting cells or tissues expressing integrin subunit α11, wherein the cells or tissues are of animal origin, comprising contacting said cells or tissues with an antibody or fragment thereof capable of binding specifically to said integrin subunit α11, or homologues or fragments thereof, or to an integrin heterodimer comprising said subunit α11 and a subunit β, or homologues or fragments thereof, wherein the integrin subunit α11 comprises essentially the amino acid sequence shown in SEQ ID NO:2. 
     
     
         51 . A method according to  claim 50 , which is a method for detecting the presence of integrin subunit α11 in cells or tissues. 
     
     
         52 . A method according to  claim 50 , which is a method for determining the differentiation-state of cells during differentiation, development, in pathological conditions, in tissue regeneration, in transplantation, or in therapeutic and physiological repair of tissues. 
     
     
         53 . A method according to  claim 52 , wherein the pathological conditions involve said integrin subunit α11. 
     
     
         54 . A method according to  claim 52 , wherein the pathological conditions are selected from the group consisting of damage of muscles, muscle dystrophy, fibrosis, wound healing, damage of cartilage and/or bone, cartilage and/or bone diseases, trauma, rheumatoid arthritis, osteoarthritis and osteoporosis. 
     
     
         55 - 56 . (canceled) 
     
     
         57 . A method according to  claim 52 , which is a method for detecting the formation of cartilage during embryonic development. 
     
     
         58 . A method according to  claim 52 , which is a method for detecting physiological or therapeutic reparation of cartilage and/or muscle. 
     
     
         59 . A method according to  claim 50 , which is a method for selecting, sorting, isolating or purifying chondrocytes and/or muscle cells. 
     
     
         60 . A method according to  claim 52 , which is a method for detecting regeneration of cartilage or chondrocytes during transplantation of cartilage or chondrocytes, or of muscle or muscle cells during transplantation of muscle or muscle cells. 
     
     
         61 . A method according to  claim 52 , which is a method for determining the differentiation-state of cells during differentiation of chondrocytes or muscle cells. 
     
     
         62 . A method according to  claim 50 , which is an in vitro method. 
     
     
         63 . A method according to  claim 50 , which is an in situ method. 
     
     
         64 . A method according to  claim 50 , which is an in vivo method. 
     
     
         65 . A method according to  claim 50 , wherein the antibody or fragment thereof is capable of binding specifically to a fragment of the integrin subunit α11, wherein said fragment of the integrin subunit α11 is a peptide chosen from the group consisting of a peptide of the cytoplasmic domain consisting essentially of the amino acid sequence KLGFFRSARRRREPGLDPTPKVLE (SEQ ID NO:3), a peptide of the I-domain consisting essentially of the amino acid sequence from about amino acid No.159 to about amino acid No. 355 of SEQ ID NO:2, and a peptide of the extracellular extension region consisting essentially of the amino acid sequence from about amino acid No. 804 to about amino acid No. 826 of SEQ ID NO:2. 
     
     
         66 - 68 . (canceled) 
     
     
         69 . A method according to  claim 50 , wherein the subunit β of the integrin heterodimer is β1. 
     
     
         70 . A method according to  claim 50 , wherein said cells are chosen from the group consisting of fibroblasts, muscle cells, chondrocytes, osteoblasts, mesenchymally derived cells and stem cells. 
     
     
         71 - 90 . (canceled) 
     
     
         91 . A pharmaceutical composition comprising as an active ingredient an antibody or fragment thereof which is capable of binding specifically to an integrin heterodimer comprising a subunit α11 and a subunit β, or to subunit α11, or to homologues or fragments of said integrin heterodimer or subunit α11, wherein the integrin subunit α11 comprises essentially the amino acid sequence shown in SEQ ID NO:2. 
     
     
         92 . A pharmaceutical composition according to  claim 91 , wherein the antibody or fragment thereof is capable of stimulating cell surface expression or activation of an integrin heterodimer comprising a subunit α11 and a subunit β, or of subunit α11, or of homologues or fragments of said integrin heterodimer or subunit α11. 
     
     
         93 . A pharmaceutical composition according to  claim 91 , which is capable of stimulating, inhibiting or blocking the formation of muscles, cartilage, bone or blood vessels. 
     
     
         94 - 95 . (canceled) 
     
     
         96 . A method for promoting adhesion of cells comprising contacting the cells with an antibody or fragment thereof capable of binding specifically to an integrin subunit α11 comprising substantially the amino acid sequence shown in SEQ ID NO:2, or to an integrin heterodimer comprising said subunit α11 and a subunit β, or to homologues or fragments of said integrin heterodimer or subunit α11. 
     
     
         97 - 102 . (canceled) 
     
     
         103 . A method according to  claim 96 , wherein the cells are chondrocytes and/or osteoblasts, wherein the antibody or fragment thereof is introduced to the surface of an implant, and wherein the antibody or fragment thereof promotes adhesion of said chondrocytes and/or osteoblasts to the surface of said implant. 
     
     
         104 . (canceled) 
     
     
         105 . A method of stimulating, inhibiting or blocking the formation of cartilage or bone, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to  claim 93 . 
     
     
         106 . An antibody or fragment thereof of  claim 12 , wherein the antibody is a monoclonal antibody. 
     
     
         107 . An antibody or fragment thereof of  claim 12 , wherein the integrin subunit α11, or homologues or fragments thereof, are recombinant or isolated. 
     
     
         108 . An antibody or fragment thereof of  claim 21 , wherein the antibody is a monoclonal antibody. 
     
     
         109 . An antibody or fragment thereof of  claim 21 , wherein the integrin heterodimer comprising a subunit α11 and a subunit β, or homologues or fragments thereof, are recombinant or isolated. 
     
     
         110 . An antibody or fragment thereof of  claim 21 , wherein the subunit β is β1. 
     
     
         111 . An antibody or fragment thereof of  claim 12 , which is capable of binding specifically to a fragment of integrin subunit α11, wherein said fragment of integrin subunit α11 is a peptide of the cytoplasmic domain comprising essentially the amino acid sequence KLGFFRSARRRREPGLDPTPKVLE (SEQ ID NO: 3). 
     
     
         112 . An antibody or fragment thereof of  claim 12 , which is capable of binding specifically to a fragment of integrin subunit α11, wherein said fragment of integrin subunit α11 is a peptide of the extracellular domain comprising essentially the extracellular extension region from about amino acid No. 804 to about amino acid No. 826 of SEQ ID NO:2. 
     
     
         113 . An antibody or fragment thereof of  claim 12 , which is capable of binding specifically to a fragment of integrin subunit α11, wherein said fragment of integrin subunit α11 is a peptide of the extracellular domain comprising essentially the I-domain from about amino acid No. 159 to about amino acid No. 355 of SEQ ID NO:2. 
     
     
         114 . A method according to  claim 50 , wherein the animal is a human.