The present invention generally relates to mutant interleukin-2 polypeptides that exhibit reduced affinity to the -subunit of the IL-2 receptor, for use as immunotherapeutic agents. In addition, the invention relates to immunoconjugates comprising said mutant IL-2 polypeptides, polynucleotide molecules encoding the mutant IL-2 polypeptides or immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant IL-2 polypeptides or immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Provided herein is a proprotein convertase subtilisin kexin type 9 (PCSK9)-specific binding protein that comprises unique complementary determining regions, that is capable of specifically binding to PCSK9, effectively inhibiting the function of PCSK9, lowering plasma LDL cholesterol level and that is useful in treating diseases associated with or impacted by the function of PCSK9.

Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.

This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.

Isolated or recombinant Eph A5 or GRP78 targeting antibodies are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and/or therapeutic treatment of human diseases, such as cancer. A method of rapidly identifying antibodies or antibody fragments for the treatment of cancer using a combination of in vitro and in vim methodologies is also provided.

The present invention generally relates to mutant interleukin-2 polypeptides that exhibit reduced affinity to the -subunit of the IL-2 receptor, for use as immunotherapeutic agents. In addition, the invention relates to immunoconjugates comprising said mutant IL-2 polypeptides, polynucleotide molecules encoding the mutant IL-2 polypeptides or immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant IL-2 polypeptides or immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Up until now, only low reactivity Tzs can be radiolabeled via direct aliphatic S.sub.N2. Unfortunately, these structures display too low reactivity for in vivo bioorthogonal chemistry approaches. Highly reactive structures such as mono-unsubstituted tetrazines (H-Tzs) have been reported to be highly sensitive to base. Extensive degradation is observed which prevents isolation of meaningful amounts for imaging studies.

In the present invention there is provided a method providing the possibility to radiolabel base sensitive tetrazine structures with significantly improved RCYs. Even tetrazines that were previously not accessible by applying standard aliphatic .sup.18F-labeling strategies can be radiolabeled. This places new classes of 18 F-fluorinated compounds within reach for application in PET imaging studies such as for diagnosis of cancers.

The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.