The invention provides diagnostic and therapeutic targets for pulmonary disease, in particular, fibrotic lung disease. The inventors have found that a genetic variant MUC5B gene is associated with increased expression of the gene, increased risk of developing a pulmonary disease, and an improved prognosis and survival among those developing the pulmonary disease.

In various embodiments the invention provides anti-mucin-like protein (MLP) monoclonal antibodies, compositions and methods for detecting MLP as a biomarker for mucin-secreting type of cancer such as ovarian or pancreatic cancer.

The invention relates to a peptidomimetic comprising or consisting of a D amino-acid sequence having at least 75% identity with SEQ ID NO: 1 or SEQ ID NO: 2, or variants or fragments thereof, in particular a peptidomimetic having the capability to interact at least with: neutrophils and/or neutrophil granules, and/or lactoferrin,and/or globet-cells and/or Muc2 proteins, and/or mucus and/or airway sputum. The peptidomimetic may have the capacity to adopt a multimeric, especially a trimeric, organization, and can be labelled,or associated with a reporter or a carrier entity, or associated with an active molecule. The invention also relates to a Solid-Phase Synthesis method for synthesizing a peptidomimetic of the invention, compositions comprising the same and use of the peptidomimetics as a medicamentor an inflammation marker or a neutrophilic inflammation marker. The invention also relates to the use of a peptidomimetic as a probe or marker for staining purposes, or to detect mucus production, or neutrophils, or to detect or monitor diseases or conditions, especially neutrophilic inflammation. The invention also relates to the use of a polypeptide comprising or consisting of SEQ ID NO: 3, or variants or fragments thereof, as probe or marker for staining lactoferrin, in particular neutrophil lactoferrin, or a probe or marker for investigating neutrophilic inflammation, especially in an imaging method.

This invention provides devices and methods for self-administered noninvasive retrieval of biological materials of the uterus and cervix, and preimplantation stage embryos. The procedure uses a Uterine Device, with a receptacle of variable volume, a controller configured to change the volume of the receptacle cavity, a flexible pouch for generation of suction to facilitate their retrieval, and an Absorption Capsule, which is a surface for collection of the above biological materials. The biological materials retrieved include cells and secretions, directly from the site of pathology, not metabolized or diluted in the body fluids, allow comprehensive analysis of various biomarkers of diseases and disorders of reproduction. Information generated by analyzing these biological materials permits early diagnosis and assessment of prognosis of diseases and disorders of the female reproductive organs, irregularities of pregnancy, anomalies of the fetus in utero, and microbial infections. The preimplantation stage embryos are recovered from normal subjects or those received treatment of gonadotrophins and/or other methods for induction of ovulation or superovulation to improve the yield of ovulated oocytes (ova). Multiple ova released from the ovaries travel through the fallopian tubes, which may be fertilized with sperms made available by artificial or normal insemination (copulation). The fertilized embryos divide and differentiate further into free preimplantation stage embryos at morula- and blastocyst-stages are deposited on the Absorption Capsule. These embryos, retrieved from the Absorption Capsule and may be processed by a variety of methods routinely utilized in the Assisted Reproductive procedures, including, screening for various genomic diseases, karyotype errors of trisomy and other chromosomal anomalies, and deleterious mutations. The screening procedures may involve Preimplantation Genetic Diagnosis (PGD) and Trophectoderm biopsy methods. Normal embryos free of disease potential are transferred to the mothers or surrogates for further in utero development. These procedures allow prevention of human birth defects and pre- and post-natal genomic diseases by selection of disease-free normal embryos for further in utero development, and possible cure of genomic diseases at this stage, in the future.

A method of diagnosing pancreatic cancer in a patient by detecting a level of one or more glycoforms of a Lewis antigen and a level of the one or more glycoforms of MUC5AC. The patient diagnosed with pancreatic cancer then may be treated for this disease. Also, a method for detecting a level of a glycan in a sample which includes using a capture reagent to immobilize the glycan on a substrate; exposing the immobilized glycan to a detection reagent; detecting the level of the immobilized glycan; and combining the biological sample with one or more pre-capture enzymes and/or exposing the immobilized glycan to one or more pre-detection enzymes.

A method of diagnosing pancreatic cancer in a patient by detecting a level of one or more glycoforms of a Lewis antigen and a level of the one or more glycoforms of MUC5AC. The patient diagnosed with pancreatic cancer then may be treated for this disease. Also, a method for detecting a level of a glycan in a sample which includes using a capture reagent to immobilize the glycan on a substrate; exposing the immobilized glycan to a detection reagent; detecting the level of the immobilized glycan; and combining the biological sample with one or more pre-capture enzymes and/or exposing the immobilized glycan to one or more pre-detection enzymes.

The present invention relates to a method for predicting the survival time of a subject suffering from renal cell carcinoma comprising the steps of: i) quantifying the percent of CD8+ T cells co-expressing PD-1 and Tim-3 in a tumor tissue sample obtained from the subject, ii) comparing the percent quantified at step i), with its corresponding predetermined reference value and iii) concluding that the subject will have a short survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is higher than its corresponding predetermined reference value or concluding that the subject will have a long survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is lower than its corresponding predetermined reference value.

The problem to be solved is to provide an anti-human MUC1 antibody Fab fragment that is expected to be useful in the diagnosis and/or treatment of a cancer, particularly, the diagnosis and/or treatment of breast cancer or bladder cancer, and a diagnosis approach and/or a treatment approach using a conjugate comprising the Fab fragment. The solution is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or 10, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a conjugate comprising the Fab fragment.

The present invention is directed to the use of (1) mucin concentration in sputum; (2) individual airway mucins MUC5AC and MUC5B ratio (MUC5AC/MUC5B) in sputum; and (3) combination of both measurements (Kesimer MUCQuant index) that can be used as an objective biomarker for differential diagnosis of smoking status and chronic bronchitis (CB), disease severity of CB (mild, moderate, and severe), exacerbation status, monitoring progression of CB, and guiding of therapies for CB. In addition, the ratio of amount of IgGFc-binding protein (FCGBP) and the amount of bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1 (or SPLUNC1)) present in a sputum sample from a subject may be used in combination with the Kesimer MUCQuant index (Kesimer MUCQuant Plus index) for differential diagnosis of smoking status and CB, disease severity of CB, exacerbation status, p monitoring progression of CB, and guiding of therapies for CB.

The problem to be solved is to provide an anti-human MUC1 antibody Fab fragment that is expected to be useful in the diagnosis and/or treatment of a cancer, particularly, the diagnosis and/or treatment of breast cancer or bladder cancer, and a diagnosis approach and/or a treatment approach using a conjugate comprising the Fab fragment. The solution is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or 10, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a conjugate comprising the Fab fragment.