Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.

The present invention is based on the finding that Netrin-(1) is retained in a stickier manner in the cell matrix at the cell periphery of the cancer cells, whereas Netrin-(1) is expressed in adults specifically in some tumors. It is also shown herein that Netrin-(1) is expressed very early during tumor formation. This makes Netrin-(1) an unexpected very specific target for imagery and/or targeted therapy. The present invention thus relates to compounds comprising an anti-Netrin-1 antibody, especially NP(137), a chelating moiety, optionally associated with a radioisotope, and their use either in imagery, diagnosis, especially companion diagnosis, or in targeted therapy. New diagnostic tests, which may be companion tests, and new cancer therapies, that may be combined to the companion test, are also proposed.

A compound represented by formula (I) is provided, wherein in formula (I), R.sub.1 and R.sub.2 each independently represents hydrogen, OR.sub.3 or SR.sub.4, at least one of R.sub.1 and R.sub.2 is OR.sub.3 or SR.sub.4, and R.sub.3 and R.sub.4 are independently a C.sub.1 to C.sub.10 alkyl group, such that the C.sub.1 to C.sub.10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of OH, NH.sub.2, halogen, ester, ether, and carboxylic acid, and M being a metal or a metal-containing compound. The compound represented by formula (I) is shown to have higher specificity to tumor cells, and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents.

##STR00001##

A compound represented by formula (I) is provided, wherein in formula (I), R.sub.1 and R.sub.2 each independently represents hydrogen, OR.sub.3 or SR.sub.4, at least one of R.sub.1 and R.sub.2 is OR.sub.3 or SR.sub.4, and R.sub.3 and R.sub.4 are independently a C.sub.1 to C.sub.10 alkyl group, such that the C.sub.1 to C.sub.10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of OH, NH.sub.2, halogen, ester, ether, and carboxylic acid, and M being a metal or a metal-containing compound. The compound represented by formula (I) is shown to have higher specificity to tumor cells, and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents. ##STR00001##

An anti-TSLP nanobody and a use thereof are provided. A coding sequence encoding the anti-TSLP nanobody, corresponding expression vector and host cell capable of expressing the nanobody, and a method for producing the anti-TSLP nanobody are also provided. The anti-TSLP nanobody has a good TSLP/TSLPR blocking activity and is expressed using pichia pastoris. Its fermenter expression yield can reach 17-23 g/L.

Methods for making heteromultimeric molecules, such as bispecific antibodies, and compositions comprising these molecules are disclosed. The methods include introducing mutations in amino acids that are in contact at the interface of two polypeptides, such that the electrostatic interaction between the ion pairs is altered.

The present invention is directed to antibodies and fragments thereof having binding specificity for TNF-. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V.sub.H, V.sub.L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-TNF- antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-TNF- antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-TNF- antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with TNF-.

Methods are disclosed for diagnosis, prognosis and therapy of acute myeloid leukemia and myelodysplastic syndromes using interleukin 1 receptor accessory protein and other targets.

The present invention provides isolated anti-interferon alpha monoclonal antibodies, particularly human monoclonal antibodies, that inhibit the biological activity of multiple interferon (IFN) alpha subtypes but do not substantially inhibit the biological activity of IFN alpha 21 or the biological activity of either IFN beta or IFN omega. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the biological activity of IFN alpha using the antibodies of the invention, as well as methods of treating disease or disorders mediated by IFN alpha, such as autoimmune diseases, transplant rejection and graft versus host disease, by administering the antibodies of the invention.

The present invention is directed to antibodies and fragments thereof having binding specificity for NGF. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V.sub.H, V.sub.L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-NGF antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-NGF antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-NGF antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with NGF.