Provided are an anti-CAIX single-domain antibody and a VHH chain thereof, as well as related coding sequence, expression vector and host cell; also provided are a production method for said CAIX single-domain antibody and an application thereof.

Disclosed herein compositions of polysaccharides chemically cross-linked by aromatic dialdehydes. The compositions may be in form of polymeric sheets for a variety of applications. Disclosed also nano-sized particles comprising the polysaccharide chemically cross-linked by aromatic dialdehydes. The nano-sized particles may further comprise lipids and surfactants. Intranasal delivery of the nano-sized particles enables delivery of biologically active agents into the brain. Topical and transdermal delivery of the nano-sized particles enables delivery of biologically active agents for treatment of systemic or dermatological disorders. Methods of manufacturing and uses of the compositions are also disclosed.

The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an anti-body-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said anti-body-drug-conjugate for the treatment of cancer.

This invention provides fully human monoclonal antibodies that recognize HER2. The invention further provides methods of using such monoclonal antibodies in a variety of therapeutic, diagnostic, and prophylactic indications.

A conjugate of formula I:
L-(D.sup.L).sub.P  (1) wherein L is a Ligand unit, D.sup.L is a Drug Linker unit of formula II: ##STR00001## wherein either: (a) R.sup.10 and R.sup.11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (b) R.sup.11 is OH, and R.sup.10 is: ##STR00002## p is an integer of from 1 to 20.

The present invention relates to an isolated antibody, which selectively binds to CLEC14A, wherein said antibody (a) comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs, wherein said heavy chain variable region comprises: (i) a variable heavy (VH) CDR1 that has the amino acid sequence of SEQ ID NO. 105, preferably of SEQ ID NO: 2 or 42; (ii) a VH CDR2 that has the amino acid sequence of SEQ ID NO. 106, preferably of SEQ ID NO: 3 or 43; and/or (iii) a VH CDR3 that has the amino acid sequence of SEQ ID NO. 107, preferably of SEQ ID NO: 4 or 44; and/or wherein said light chain variable region comprises: (iv) a variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO. 108, preferably of SEQ ID NO: 6 or 46; (v) a VL CDR2 that has the amino acid sequence of SEQ ID NO. 109, preferably of SEQ ID NO: 7 or 47; and/or (vi) a VL CDR3 that has the amino acid sequence of SEQ ID NO. 1 10, preferably of SEQ ID NO: 8 or 48; or (b) comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs, wherein said heavy chain variable region comprises: (i) a variable heavy (VH) CDR1 that has the amino acid sequence of SEQ ID NO: 22; (ii) a VH CDR2 that has the amino acid sequence of SEQ ID NO: 23; and/or (iii) a VH CDR3 that has the amino acid sequence of SEQ ID NO: 24; and/or wherein said light chain variable region comprises: (iv) a variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO: 26; (v) a VL CDR2 that has the amino acid sequence of SEQ ID NO: 27; and/or (vi) a VL CDR3 that has the amino acid sequence of SEQ ID NO: 28; or (c) is an antibody which can compete with antibody (a) or (b) for binding to CLEC14A. The invention further provides chimeric antigen receptors, nucleic acid molecules encoding the antibodies of the invention or the chimeric antigen receptors, vectors, cells and methods/uses of the antibodies and chimeric antigen receptors.

The present invention provides a multi-drug-loading site and high drug-loading capacity ligand-drug conjugate. The ligand-drug conjugate has a structure of general formula (I). The ligand-drug conjugate has the characteristics of high loading capacity, high drug efficacy, low toxicity, and low risks. The ligand-drug conjugate can be used particularly to connect to a low toxicity chemical molecule, thereby extending a therapeutic window. Furthermore, the present invention provides an antibody-drug conjugate molecule. The antibody-drug conjugate molecule has the characteristics of multiple drug-loading ability and high drug-loading capacity, such that the antibody-drug conjugate can carry a large amount of a low toxicity chemical molecule and achieve a therapeutic effect without depending on antibody targeting or high toxicity chemicals.
TM-{R.sup.2-PEG1-[R.sup.1-PEG2-(R.sup.3-A′-D).sub.n].sub.m}.sub.l  (I

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

The present invention provides methods of testing anti-STn antibodies for their ability target cancer stem cells by isolating cancer stem cells from cultures, contacting them with anti-STn antibodies being tested, and measuring resulting cell viability.

Compositions and methods for treating ovarian cancer are provided. Methods include combined treatment with chemotherapeutic agents and anti-STn antibodies. Chemotherapy resistant ovarian cancer cells may be reduced. Chemotherapy resistant ovarian cancer cells may include cancer stem cells.