Abstract: Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure of Lv-[(LU)0-1-(D)1-4]p wherein L- is Ligand unit; LU is a Linker unit (LU); v is 1; p is an number ranging from about 1 to about 20; and D is a drug moiety having the formula: wherein the moiety —N(R9)Z1 is a phenylalanine bioisostere, wherein Z1 is —CH(R10)Z2 so that the phenylalanine bioisostere has the structure of Formula A: and wherein the substituents R2-R10, X1 and Z2 are as defined.

Abstract: The present invention provides for the treatment of multiple sclerosis through the use of chimeric and humanized versions of anti-CD19 antibodies that may mediate ADCC, CDC, and/or apoptosis.

Abstract: The peptides of formula (I) R1—(X)K—P—Y, where: R1 is the group attached to the N-terminal of the first amino acid of the sequence P, optionally via the ligand X, and is selected from H, CH3C(?O)—, and maleimide; X is a biradical selected from —NH—(CH2)r—C(?O)—, —C(?O)—(CH2)r—C(?O)—, —S(CH2)r—, —S—(CH2)r—C(?O)—, —O—(CH2)r—, —S—CH2—CH(NH2)—C(?O)—, —O—(CH2)r—C(?O)—, —(CH2)r—C(?O)—, —NH—O—CH2—C(?O)—NH—(CH2)r—CH(NH2)—C(?O)—, —(CH2)r—C(?O)—NH—(CH2)r—CH(NH2)—C(?O)—, and —NH—(CH2)r—CH(NHC(?O)CH2NH2)—C(?O)—; r is 1-5; P is a biradical of an amino acid sequence comprising the sequence D-Pro-D-Trp-D-Val-D-Pro-D-Ser-D-Trp-D-Met-D-Pro-D-Pro-D-Arg-D-His-D-Thr (SEQ ID NO: 1); Y is the group attached to the C-terminal of the last amino acid of the sequence P, and is selected from —NH2, —OH, —OR2 and —NHR2; R2 is a radical selected from (C1-C6)-alkyl and (CH2)2—NH—C(?O)—CH2—O—NH2; k is 0-2; m is 0-1; with the proviso that when the biradical X is —C(?O)(CH2)rC(?O)—, then R1 is H; when the N of the amino acid of the sequence P

Abstract: The present invention relates to a linker for forming conjugates of a protein or peptide with a therapeutically active agent and which comprise a thiomaleamic acid moiety that is susceptible to cleavage under the pH conditions prevalent in the lysosome.

Abstract: The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.

Abstract: The invention described herein relates to novel nucleic acid sequences and their encoded proteins, referred to as 158P1D7 and variants thereof, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers that express 158P1D7 and variants thereof.

Abstract: Methods and compositions are provided for the diagnosis and treatment of colorectal cancers associated with amplification or overexpression of the FGFR2 gene.

Abstract: The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures.

Abstract: The invention provides methods for attaching drugs, dyes or radiolabels to bis-MTX. This method can be used to prepare bis-MTX analogs that can be used to deliver agents, such as nanoparticles, drugs, dyes or radiolabels, to cells.

Abstract: Antibodies are engineered by replacing one or more amino acids of a parent antibody with non cross-linked, highly reactive cysteine amino acids. Antibody fragments may also be engineered with one or more cysteine amino acids to form cysteine engineered antibody fragments (ThioFab). Methods of design, preparation, screening, and selection of the cysteine engineered antibodies are provided. Cysteine engineered antibodies (Ab), optionally with an albumin-binding peptide (ABP) sequence, are conjugated with one or more drug moieties (D) through a linker (L) to form cysteine engineered antibody-drug conjugates having Formula I: Ab-(L-D)p??I where p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.

Abstract: Disclosed are methods and compositions for the detection, diagnosis, prognosis, and therapy of hematological malignancies, and in particular, B cell leukemias, lymphomas and multiple myelomas. Disclosed are compositions, methods and kits for eliciting immune and T cell responses to specific malignancy-related antigenic polypeptides and antigenic polypeptide fragments thereof in an animal. Also disclosed are compositions and methods for use in the identification of cells and biological samples containing one or more hematological malignancy-related compositions, and methods for the detection and diagnosis of such diseases and affected cell types. Also disclosed are diagnostic and therapeutic kits, as well as methods for the diagnosis, therapy and/or prevention of variety of leukemias and lymphomas.

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

Abstract: Methods to improve the success of cancer therapies that target the human folate receptor 1 are provided. Kits comprising reagent useful in the methods are further provided.

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

Abstract: Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.

Abstract: The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

Abstract: An antibody-conjugated double-emulsion nanocapsule is provided. A linking group is introduced on the surface of a double-emulsion nanocapsule, which is composed of an oily shell enclosing an aqueous core, to link the double-emulsion nanocapsule with an antibody.

Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

Abstract: The invention is a method for the differential diagnosis of chronic schizophrenia or chronic alcoholism, by imaging the brain of a subject to detect any or all of the markers phosphocreatine (PCr), N-acetyl aspartate divided by the total creatine signal (NA/Crt), and synaptic phosphodiester (sPDE), and determining any increase or decrease in the presence of such markers compared to normal levels in specified anatomic areas of the brain. The output of such a method, resulting from such imaging, is presented to be viewed by a diagnostician in order to support the differential diagnosis based on the data output.

Abstract: The invention relates to therapeutic conjugates with the ability to target various antigens. The conjugates contain a targeting antibody or antigen binding fragment thereof and an anthracycline chemotherapeutic drug. The targeting antibody and the chemotherapeutic drug are linked via a linker comprising a hydrazide moiety.

Abstract: The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-?2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

Abstract: The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

Abstract: Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2-pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2-PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKK?/? and I?B?, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Abstract: The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Abstract: This invention is related to a pharmaceutical combination that contains a Casein kinase 2 (CK2) peptide inhibitor (termed P15) along with the standard chemotherapeutic drugs used in cancer treatment and which are administered together, separated or sequentially. The chemotherapeutic drugs include cisplatin, taxol, alkaloids from Vinca, 5-fluorouracil, doxorubicin, cyclophosphamide, etoposide, mitomicin C, imatinib, iressa and velcade (vortezomib). The synergism between the P15 peptide and the anticancer drugs achieves an efficient concentration of each cytostatic drug in the combination which is from 10- to 100-fold lower than that for each cytostatic drug alone. The pharmaceutical combination described in this invention exhibits lower toxicity compared to that reported by the anticancer therapeutics and therefore, it represents a crucial advantage for its use in cancer therapy.

Abstract: The present invention relates to methods of treating treating epidermal growth factor deletion mutant vIII (EGFRvIII) related disorders, such as glioblastoma or anaplastic astrocyte tumors, using antigen binding proteins, including antibodies against EGFRvIII conjugated to a drug. Diagnostic and therapeutic formulations of such antibodies and drug conjugates thereof are also provided.

Abstract: The invention is directed to antibody drug conjugate compositions of matter useful for the diagnosis and treatment of tumors in mammals and to methods of using those compositions of matter for the same.

Abstract: The present invention relates to anti-FGFR2 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

Abstract: Anti-5T4 antibodies, anti-5T4 antibody/drug conjugates, and methods for preparing and using the same.

Abstract: This invention relates to pyrrolobenzodiazepines (PBDs), in particular pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position in each monomer unit, and their inclusion in targeted conjugates. The differing substituent groups may offer advantages in the preparation and use of the compounds, particularly in their biological properties and the synthesis of conjugates, and the biological properties of these conjugates.

Abstract: An immunoconjugate in which a phosphate-prodrugged DNA minor groove binding agent of formula (I), where X is a nucleophilically displaceable leaving group, is conjugated to an antibody or an antigen binding fragment of an antibody, and compounds that can be used for making such immunoconjugates, and uses of such immunoconjugates.

Abstract: The current disclosure provides binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof (e.g., antibody-drug conjugates or ADCs), comprising a site-specifically engineered drug-glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Abstract: This invention relates to antibody drug conjugates and methods of use thereof. More particularly, antibody drug conjugates comprising a cytoprotective agent are provided, wherein the conjugates are useful for the treatment of proteinopathies such as Alzheimer's disease.

Abstract: Conjugate compounds of formula (A): wherein: R2 is where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, where

Abstract: A novel gene 0161P2F10B (also designated 161P2F10B) and its encoded protein, and variants thereof, are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 161P2F10B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 161P2F10B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 161P2F10B can be used in active or passive immunization.

Abstract: The invention provides a stable formulation comprising an anti-EGFR antibody drug conjugate (ADC), including an anti-EGFR antibody, e.g., antibody 1, conjugated to an auristatin, e.g., MMAF, histidine, a sugar, and a surfactant.

Abstract: The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

Abstract: A compound, or a pharmaceutically acceptable salt or solvate thereof, or conjugates thereof, selected from the group consisting of formula wherein: (a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is S02M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically acceptable cation.

Abstract: The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

Abstract: Provided are monoclonal antibodies and antigen binding fragments thereof that specifically bind vascular endothelial growth factor (VEGF). The anti-VEGF monoclonal antibodies block VEGF binding to its receptors (e.g., VEGFR1 and/or VEGFR2) and prevent phosphorylation of VEGFR2 by VEGF. Also provided are methods of using the monoclonal anti-VEGF antibodies for treatment of disease, including cancer.

Abstract: The present disclosure relates to immunoglobulins and immunoglobulin conjugates with reduced oligomerization and efficient labeling and compositions, methods of generating such immunoglobulins and immunoglobulin conjugates and methods of using such immunoglobulin conjugates particularly in the treatment and prevention of disease.

Abstract: Antibodies which specifically bind heregulin-coupled HER3, at a site distinct from the heregulin binding site, are described. These antibodies are particularly useful in treating cancer.

Abstract: Disclosed are monoclonal antibodies that specifically bind to the B7 family member B7H6, including antibodies capable of inhibiting the interaction of B7H6 with NKp30. Also disclosed are anti-B7H6 antibody-drug conjugates comprising an anti-B7H6 monoclonal antibody conjugated to a therapeutic agent. The anti-B7H6 antibodies and antibody-drug conjugates are useful in methods for exerting therapeutic effects against B7H6-expressing cells, as well as in diagnostic methods for the detection of B7H6 or B7H6-expressing cells.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: The present invention relates to methods of diagnosing, and methods of treating, hepatocellular carcinoma in a subject. The invention also relates to polypeptide antagonists of PLVAP proteins, including humanized and chimeric antibodies that specifically bind PLVAP proteins, as well as compositions and kits comprising such polypeptide antagonists.

Abstract: The invention provides compositions and methods for the targeted bacteriostatic and antibacterial agents and for treatment of sepsis caused by infectious diseases, such as bacterial and fungal diseases. In one aspect, the invention provides methods and compositions for decreasing the levels of LPS in the circulation of an individual, e.g., a human patient with sepsis, e.g., gram negative septic shock. In one aspect, the invention is directed to chimeric proteins comprising the MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. In one aspect, the invention is directed to chimeric proteins comprising fragments or altered form of MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. The invention also provides pharmaceutical compositions comprising the chimeric polypeptides of the invention, and methods of making and using them, including methods for ameliorating or preventing sepsis.

Abstract: A compound with the formula I: wherein: R2 is of formula II: where A is a C5-7 aryl group, X is selected from the group comprising: NHNH2, CONHNH2, formula III, formula IV, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is —CH?CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; either: (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the n

Abstract: The present application is directed to covalent conjugates between an isocarbostyril alkaloid and a lipophilic biomolecule, to pharmaceutical compositions comprising the conjugates and to therapeutic uses thereof, in particular for treating cancer.