The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I:

A-(L-D)p (I)

or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds FAP; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

The current invention relates to: procoagulant proteins which may, for example, be fusion proteins or chemical conjugates; methods of producing said procoagulant proteins; polynucleotides that encode said fusion proteins and cells that expresses them. Furthermore, the current invention relates to procoagulant proteins for use as a medicament. Individuals that have a coagulopathy, such as haemophilia A and B with or without inhibitors, may be treated with the procoagulant proteins of the current invention.

[Problems] To provide a technique for efficiently incorporating an agent having to function in muscle tissue, which is not sufficiently incorporated into muscle tissue when administered in body, into muscle tissue, particularly muscle tissue composed of skeletal muscle or cardiac muscle. [Solution] A conjugate of an anti-human transferrin receptor antibody and an agent, wherein the agent is a biologically active agent that should function in muscle tissue, e.g., a lysosomal enzyme such as acid ?-glucosidase, ?-galactosidase A.

The present disclosure provides antibodies and antigen-binding fragments that target transferrin receptor. Also provided is the use of these antibodies and antigen-binding fragments as carriers to deliver therapeutic molecules across the blood-brain barrier.

Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibody provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in Tay Sachs disease (TSD), Nieman Pick Disease (NPD), or Neuronal Ceroid Lipofuscinosis 1 (NCL1), which are caused by mutations in the respective lysosomal enzymes, hexosaminidase A (HEXA), acid sphingomyelinase (ASM), and palmitoyl-protein thioesterase 1 (PPT1). The fusion antibodies provided herein comprise HEXA, ASM, and PPT1. The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.

Variant Erwinia chrysanthemi L-asparaginases with reduced L-glutaminase activity and enhanced in vivo circulation are described as are fusion proteins containing an L-asparaginase and three tandem soluble domains of TRAIL for use in the treatment of cancers such as acute lymphoblastic leukemia and acute myeloid leukemia.

The present invention relates to a conjugate in which an immunoglobulin Fc region is linked to therapeutic enzymes through a non-peptide polymer linkage moiety, and more specifically, to a conjugate in which a non-peptide polymer linkage moiety is specifically linked to an immunoglobulin Fc, a method of preparing the same, and a composition comprising the same.

Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

The present disclosure provides for compositions comprising a chimeric polypeptide comprising a polypeptide effective for treating glycogen storage disease and an internalizing moiety that promotes delivery into cells. In certain embodiments, the polypeptide effective for treating glycogen storage disease is an acid alpha-glucosidase (GAA), a laforin, an amyloglucosidase (AGL), a malin, or an alpha amylase. The present disclosure also provides for methods for decreasing glycogen accumulation in cells or for treating glycogen storage diseases, including Forbes-Cori Disease, Andersen Disease, von Gierke Disease, Pompe Disease, and Lafora Disease, comprising administering the chimeric polypeptide disclosed herein.

Provided herein are methods and compositions for treating a subject suffering from a deficiency in -L-Iduronidase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an -L-Iduronidase. A therapeutically effective systemic dose is based on the specific CNS uptake characteristics of human insulin receptor antibody--L-Iduronidase fusion antibodies as described herein.