Provided are a vesicle and the use thereof. The vesicle is an induced vesicle, and the sources thereof include stem cells or somatic cells, and the possessed markers include Syntaxin 4. Compared with an exosome in mesenchymal stem cells, the vesicle can specifically express Syntaxin 4 and can be used to distinguish characteristic markers of MSC-derived vesicles and exosomes. The vesicle can play a procoagulant effect in vitro, can improve the bleeding tendency of mice with hemophilia after in vivo injection, and can be used for the treatment of improving the bleeding tendency of hemophilia. In addition, the vesicle can be expelled through the skin and hair.

The present invention relates to an antigen-binding protein, or an antigen-binding fragment thereof, comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence GYSITSGYSWH; a VHCDR2 having the amino acid sequence YIHYSGSTKYNPSLKS and a VHCDR3 having the amino acid sequence GSNYGFDY; and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence KSSQSLLYSNDQKNYLA, a VLCDR2 having the amino acid sequence WASIRES, and a VLCDR3 having the amino acid sequence QQYYIYPLT. The present invention also relates to an antigen-binding protein, or an antigen-binding fragment thereof, comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence VYSITSGYSWH; a VHCDR2 having the amino acid sequence YIHYSGSTKYNPSLKS, and a VHCDR3 having the amino acid sequence GTDNAVDY; and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence KSSQSLLYSSNQKNYLA, a VLCDR2 having the amino acid sequence WAS SRES, and a VLCDR3 having the amino acid sequence QQYYIYPLT. Compositions comprising the antigen-binding protein, or antigen-binding fragment thereof, methods of use of the antigen-binding protein, or antigen-binding fragment thereof and kits comprising the antigen-binding protein, or antigen-binding fragment thereof are also provided.

The present invention relates to an antigen-binding protein, or an antigen-binding fragment thereof, comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence GYSITSGYSWH; a VHCDR2 having the amino acid sequence YIHYSGSTKYNPSLKS and a VHCDR3 having the amino acid sequence GSNYGFDY; and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence KSSQSLLYSNDQKNYLA, a VLCDR2 having the amino acid sequence WASIRES, and a VLCDR3 having the amino acid sequence QQYYIYPLT. The present invention also relates to an antigen-binding protein, or an antigen-binding fragment thereof, comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence VYSITSGYSWH; a VHCDR2 having the amino acid sequence YIHYSGSTKYNPSLKS, and a VHCDR3 having the amino acid sequence GTDNAVDY; and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence KSSQSLLYSSNQKNYLA, a VLCDR2 having the amino acid sequence WAS SRES, and a VLCDR3 having the amino acid sequence QQYYIYPLT. Compositions comprising the antigen-binding protein, or antigen-binding fragment thereof, methods of use of the antigen-binding protein, or antigen-binding fragment thereof and kits comprising the antigen-binding protein, or antigen-binding fragment thereof are also provided.

The present invention relates to a biomarker for early stage ovarian cancer. Specifically, expression of the biomarker Annexin A2 is higher in the plasma of subjects with early stage ovarian cancer. Accordingly, methods of detecting early stage ovarian cancer in a subject, of identifying a subject having early stage ovarian cancer, and of determining if a subject is susceptible to developing ovarian cancer, are provided. Also provided are methods of screening candidate therapeutic agents for use in treating early stage ovarian cancer, and compositions and kits for detecting early stage ovarian cancer in a subject, for identifying a subject having early stage ovarian cancer, and for determining if a subject is susceptible to developing ovarian cancer.

The present invention relates to an antigen-binding protein, preferably a monoclonal antibody, against annexin A2 (ANXA2), comprising (i) a heavy chain variable domain comprising a VHCDR1 of sequence GYSITSGYSWH, a VHCDR2 of sequence YIHYSGSTKYNPSLKS and a VHCDR3 of sequence GSNYGFDY; and (ii) a light chain variable domain comprising a VLCDR1 of sequence KSSQSLLYSNDQKNYLA, a VLCDR2 of sequence WASIRES, and a VLCDR3 of sequence QQYYIYPLT. Also provided is an ANXA2 binding protein comprising (i) a heavy chain variable domain comprising a VHCDR1 of sequence VYSITSGYSWH; a VHCDR2 of sequence YIHYSGSTKYNPSLKS, and a VHCDR3 of sequence GTDNAVDY; and (ii) a light chain variable domain comprising a VLCDR1 of sequence KSSQSLLYSSNQKNYLA, a VLCDR2 of sequence WASSRES, and a VLCDR3 of sequence QQYYIYPLT. The antibodies preferably bind to an N-linked glycan on ANXA2, and are internalised upon binding. They may be conjugated with cytotoxins and may be used in the treatment or detection of cancer.

The present invention relates to a method for diagnosing the occurrence of a vascular dysfunction or a vascular injury in a subject, said method comprising a step consisting of determining in a plasma sample obtained from said subject the level of free annexin. The present invention further relates to a method for determining whether a subject is at risk for severe vasculopathy, cardiovascular complications and cardiovascular disease, said method comprising a step consisting of determining in a plasma sample obtained from said subject the level of free annexin. Preferably, the methods further comprise the steps consisting of determining the level of circulating phosphatidylserine positive (PS+) microparticles (MPs) in the plasma sample obtained from said subject and calculating the ratio free annexin/circulating PS+MPs. The invention also relates to a kit for use in a method according to the invention and to a phosphatidylserine antagonist, for use in a method of treatment of severe vasculopathy, cardiovascular complications and cardiovascular disease in a subject having a decreased level of free annexin as compared to a free annexin reference level, wherein the method comprises a determination of the free annexin level in a plasma sample of said subject. Preferably, a phosphatidylserine antagonist is for use in a method of treatment of severe vasculopathy, cardiovascular complications and cardiovascular disease in a subject having a decreased ratio of free annexin/circulating PS+MPs as compared to a free annexin/circulating PSMPs reference ratio, wherein the method further comprises the steps consisting of determining the circulating PS+MPs level in said plasma sample and calculating the free annexin/circulating P8MPs ratio.

The present disclosure relates to methods of collecting exosomes and microvesicles (EMV) from urine, isolating corresponding mRNA, and analyzing expression patterns in order to diagnose and treat various post-kidney transplant complications. In particular, annexin1 mRNA expression patterns are analyzed through a unique diagnostic formula.

The present invention relates to a biomarker for early stage ovarian cancer. Specifically, expression of the biomarker Annexin A2 is higher in the plasma of subjects with early stage ovarian cancer. Accordingly, methods of detecting early stage ovarian cancer in a subject, of identifying a subject having early stage ovarian cancer, and of determining if a subject is susceptible to developing ovarian cancer, are provided. Also provided are methods of screening candidate therapeutic agents for use in treating early stage ovarian cancer, and compositions and kits for detecting early stage ovarian cancer in a subject, for identifying a subject having early stage ovarian cancer, and for determining if a subject is susceptible to developing ovarian cancer.

Methods of screening for expression of an RNA associated with a post-kidney transplant complication include collecting vesicles from urine, isolating vesicle-associated RNA, and analyzing expression patterns. In particular, AIF1, BTN3A3, CCL5, CD48, HAVCR1, or SLC6A6 mRNA expression patterns are analyzed.

Provided herein is a method for diagnosing/prognosing a metastatic cancer in a subject by measuring and detecting one or more of CS-ANXA2, DCAMKL, Lgr5 or CS-ANAX2 and DCAMKL or CS-ANXA2 and Lgr5 positive circulating tumor stem cells in the subject's blood or plasma. Also provided is a method for distinguishing the presence of early stage primary cancer from advanced stage metastatic cancer in the subject by measuring and detecting AnnexinA2, CS-ANXA2 and DCAMKL-1 or Lgr5 in the blood or plasma. In addition, there is provided a method for distinguishing the presence of benign, pre-cancerous tumorous growths or cancerous tumors in the subject by measuring and detecting AnnexinA2 and circulating tumor stem cells positive for CS-ANXA2 and DCAMKL or CS-ANXA2 and Lgr5 in the blood or plasma.