The present invention relates to monoclonal antibodies to angiotensin-(1-12) as well as compositions comprising the same and methods of using the same.

Subject matter of the present invention is a method for monitoring a therapy in a subject, wherein the subject is under treatment with an anti-Adrenomedullin (ADM) binder selected from the group comprising an antibody, antibody-fragment and/or non-Ig scaffold, comprising determining the level of a fragment of pre-pro-Adrenomedullin selected from the group comprising Midregional Proadrenomedullin (MR-proADM), C-terminal Proadrenomedullin (CT-proADM) and/or Proadrenomedullin N-terminal 20 peptide (PAMP) or fragments thereof in a bodily fluid obtained from said subject; and correlating the level of said fragment of pre-pro-Adrenomedullin with the subject's clinical/medical status of health and/or the risk for an adverse outcome and/or the requirement for adapting therapeutic measures.

Chimeric Fc fusion polypeptides are provided, optionally including biologically active polypeptides for therapeutic use.

Chimeric Fc fusion polypeptides are provided, optionally including biologically active polypeptides for therapeutic use.

The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.

The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.

The inventors have produced two high specificity and high affinity monoclonal antibodies that bind to human neuromedin U (NMU). Methods and compositions are provided for treating an individual in need thereof (e.g., an individual who is obese and/or has diabetes) by administering an anti-NMU/NMUR agent (e.g., an anti-NMU antibody). For example, methods and compositions are provided for increasing circulating insulin in an individual. Methods and compositions are also provided for detecting neuromedin U (NMU) (e.g., in a biological sample such as serum). Methods and compositions are also provided for predicting whether an individual will develop diabetes and/or PDAC, and for identifying an individual who would benefit from administration of an anti-NMU/NMUR agent.

The inventors have produced two high specificity and high affinity monoclonal antibodies that bind to human neuromedin U (NMU). Methods and compositions are provided for treating an individual in need thereof (e.g., an individual who is obese and/or has diabetes) by administering an anti-NMU/NMUR agent (e.g., an anti-NMU antibody). For example, methods and compositions are provided for increasing circulating insulin in an individual. Methods and compositions are also provided for detecting neuromedin U (NMU) (e.g., in a biological sample such as serum). Methods and compositions are also provided for predicting whether an individual will develop diabetes and/or PDAC, and for identifying an individual who would benefit from administration of an anti-NMU/NMUR agent.

A method for non-surgical neutering or castration of a non-human mammal for AAV-mediated delivery of an anti-GnRH polypeptide to a non-human animal is described. More particularly, the animal is administered an adeno-associated virus (AAV) vector having an AAV capsid having packaged therein nucleic acid sequences comprising an AAV 5′ inverted terminal repeat (ITR), a sequence encoding a polypeptide which specifically binds gonadotropin releasing hormone (GnRH) under control of regulatory sequences which direct expression of the polypeptide, and an AAV 3′ ITR. A composition comprising the AAV-anti-GnRH may also be used for inhibiting tumor growth in a mammal with a cancer responsive to gonadal steroid hormones.

A method for non-surgical neutering or castration of a non-human mammal for AAV-mediated delivery of an anti-GnRH polypeptide to a non-human animal is described. More particularly, the animal is administered an adeno-associated virus (AAV) vector having an AAV capsid having packaged therein nucleic acid sequences comprising an AAV 5′ inverted terminal repeat (ITR), a sequence encoding a polypeptide which specifically binds gonadotropin releasing hormone (GnRH) under control of regulatory sequences which direct expression of the polypeptide, and an AAV 3′ ITR. A composition comprising the AAV-anti-GnRH may also be used for inhibiting tumor growth in a mammal with a cancer responsive to gonadal steroid hormones.