Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH.sub.4.sup.+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

The invention provides methods for producing soluble di-chain BoNT/A protein.

Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.

There is described a method for extracting a target chemical compound from a cellular material in a sample. The method comprising the steps of: subjecting the sample to mechanical lysis to cause disruption of a cellular membrane in the cellular material; contacting the sample with an alkaline material to produce a lysate composition comprising the target chemical compound; and recovering the lysate composition from the sample. There is also described a method for producing a lysate composition comprising RNA from a mammalian bodily fluid sample comprising a cellular material. There is also described a method for extracting a nucleic acid from a cellular material in a bodily fluid or an inoculant derived therefrom.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

Methods and pharmaceutical compositions for treating ischemic injury are provided. The methods include administering a therapeutically effective amount of a vascular matrix metalloproteinase 9 (MMP-9) inhibitor that reduces ischemic injury in a subject.

he disclosure relates to the engineering of collagen-binding modification of masked therapeutic agents comprising one or more tumor-associated protease cleavage sites. Upon exposure to tumor-associated proteases in the tumor microenvironment, the polypeptide is cleaved, which unmasks the therapeutic agent, reducing off-target side effects and toxicity associated with systemic administration. Accordingly, aspects of the disclosure relate to a polypeptide comprising a therapeutic agent linked to a masking agent through a linker, wherein the linker comprises one or more tumor-associated protease cleavage sites, and wherein the masking agent blocks the association of the therapeutic agent to its therapeutic target, and further wherein the polypeptide is operatively linked to a collagen binding domain or a tumor-targeting agent.

This disclosure provides methods and compositions for treating TTP based on transfusion of a relatively small number of genetically modified red blood cells. The genetically modified red blood cells express a fusion protein including a fragment of ADAMTS13 that is enzymatically active against von Willebrand factor (VWF). The fragments of ADAMTS13 can be resistant to the inhibitors, e.g., the auto-immune antibodies, which are responsible for the acquired form of TTP.

This disclosure provides ADAM8 modulating peptides, nucleic acids encoding ADAM8 modulating peptides, and methods for using the same to modulate ADAM8 biological activities in vitro and/or in vivo, to inhibit ADAM8 biological activities associated with diseases or disorders in subjects including gene therapy or cell based therapies. Specifically, methods are provided to decrease inflammation, and to inhibit undesirable cellular proliferation, fibrosis, and angiogenesis. In some embodiments, the ADAM8 modulating peptides or nucleic acids encoding them include modifications of one or more amino acids of the human ADAM8 prodomain amino acid sequence, and in some embodiments the ADAM8 modulating peptides include other modifications such as but not limited to the addition of PEG groups.