Enzo Biochem, Inc.

Enzo Diagnostics, Inc.

Enzo Therapeutics, Inc.

Enzo Life Sciences, Inc. C/o Enzo Biochem, Inc.

Other

University of Connecticut

Enzo Life Sciences, Inc.

St. Jude's Childrens Hospital

Enzo Therapeutics, Inc. C/o Enzo Biochem, Inc.

Li, Xiaofeng

Liu, Peng

Engelhardt, Dean

Liu, Wenzhong

Dean L Engelhardt

Elazar S Rabbani

Jannis G Stavrianopoulos

James J Donegan

Dollie Kirtikar

Stanley Kline

Dakai Liu

Xiaofeng Li

James G Wetmur

Dianqing Wu

Norman E Kelker

Robin S Quartin

Peng Liu

Elazar Rabbani

Jufang Shan

Yaron Ilan

Robert G Pergolizzi

Maya Margalit

Yazhou Zhang

Ari Zimran

Jayanta Roy-Chowdhury

Israel Gotsman

Janes G Stavrianopoulos

Wenzhong Liu

Jie Zhang

Norman E Keller

Paula J Olsiewski

Stan Kline

Yaron Iian

A method of detecting in a sample an analyte (A) having a molecularly recognizable portion thereon, which comprises: providing (B) a molecular bridging entity having thereon: (i) a portion capable of recognizing the molecularly recognizable portion on the analyte; and (ii) a portion comprising a polynucleotide sequence; and (C) a signalling entity having thereon: (i) a polynucleotide portion capable of annealing to the polynucleotide portion of the bridging entity, thereby to form a stable polynucleotide hybrid, and (ii) a signal generating portion; forming a complex comprising: (1) the analyte (A) complexed through its molecularly recognizable portion to (2) the recognizing portion of the entity (B); the entity (B) being complexed through the polynucleotide portion thereon to (3) the polynucleotide portion of the signalling entity; and detecting a signal by means of the signal generating portion present in the complex.

Analyte detection utilizing polynucleotide sequences, composition, process and kit

The present invention provides an array of compositions useful for effecting and/or exhibiting changes in biological functioning and processing within cells and in biological systems containing such cells. In effect, these compositions combine chemical modifications and/or ligand additions with biological functions. The chemical modifications and/or ligand additions provide additional characteristics to the compositions without interfering substantially with their biological function. Such additional characteristics include nuclease resistance, targeting specific cells or specific cell receptors localizing to specific sites within cells and augmenting interactions between the compositions and target cells of interest as well as decreasing such interactions when desired. Also provided by the present invention are processes and kits.

Non-ionically bound constructs, and compositions and kits comprising domains

Property effecting and/or property exhibiting compositions for therapeutic and diagnostic uses

The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 that is required for the coreceptors' transport to cell surfaces, resulting in less LRP5 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkk1, we believe that the G171V mutation may cause an increase in Wnt activity in osteoblasts by reducing the number of targets for paracrine Dkk1 to antagonize without affecting the activity of autocrine Wnt.

Compositions and methods for bone formation and remodeling

Compositions and methods for the treatment of bone diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2), acts to stimulate bone formation independently of Wnt proteins which may be inhibited and/or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

Compositions and methods for the stimulation or enhancement of bone formation and the self-renewal of cells

A process for determining the sequence of nucleic acids of interest employs nucleotides or nucleotide analogs that have been made detectable by non-radioactive modifying or labeling. Such nucleotides or nucleotide analogs are modified on the sugar moieties, the phosphate moieties or the base moieties, including base analogs. Modified nucleotide analogs can be attached to or coupled to or incorporated into DNA or RNA. The modified or labeled nucleotides or nucleotide analogs are also useful in processes for detecting the presence of nucleic acids of interest and for characterizing chromosomal sequences. Detection processes using the modified or labeled nucleotides or nucleotide analogs extend to the use of a gel for separating or resolving hybrids formed between non-radioactively labeled oligonucleotides or polynucleotides and such nucleic acids of interest.

Nucleic acid sequencing processes using non-radioactive detectable modified or labeled nucleotides or nucleotide analogs, and other processes for nucleic acid detection and chromosomal characterization using such non-radioactive detectable modified or labeled nucleotides or nucleotide analogs

This invention provides novel processes for therapeutic applications, including the treatment of subjects carrying infectious agents or having impaired autoimmunity or impaired immune condition. The therapeutic applications disclosed herein are also directed at the treatment of cancerous subjects with malignant tumors containing cancerous cells or malignant or cancerous cells. Vaccination processes for preventing infections in subjects are also provided. The novel processes comprise introducing into or administering to a subject one or more antigens, or trained or adopted immune cells. These antigens or immune cells are capable of establishing or increasing at least one first specific immune response and decreasing at least one second specific immune response. Such responses include components, such as cellular immune reaction elements, humoral immune reaction elements and cytokines, the latter also encompassing interferons and lymphokines. Useful compositions are also provided by this invention.

Therapeutic processes and useful compositions therefor

The present invention provides a nucleotide having the formula, wherein PM is a phosphate moiety, SM is a ribose or a deoxyribose sugar moiety, and BASE is a pyrimidine, purine or 7-deazapurine moiety. PM is attached to SM at a position independently selected from the 2', 3&#x2032;, and 5&#x2032; positions of SM when the nucleotide is a ribonucleotide, and at a position independently selected from the 3&#x2032; and 5&#x2032; positions when the nucleotide is a deoxyribonucleotide. BASE is attached to the 1&#x2032; position of SM from the Nposition when BASE is a pyrimidine, or the Nposition when BASE is a purine or 7-deazapurine. Sig is a detectable moiety covalently attached to SM directly or through a linkage group. Also provided are an oligo- or polynucleotide comprising at least one such sugar moiety labeled nucleotide, and other compositions including those wherein a polypeptide is terminal ligated or attached to the oligo- or polynucleotide. The sugar moiety labeled nucleotide, and the oligo- or polynucleotides and other compositions comprising such nucleotides, are useful as diagnostic tools for detecting analytes and as therapeutic agents.

Sugar moiety labeled nucleotide, and an oligo- or polynucleotide, and other compositions comprising such sugar moiety labeled nucleotides

The present invention provides a nucleotide having the formula,Sig-PM-SM-BASEwherein PM is a phosphate moiety, SM is a sugar moiety and BASE is a pyrimidine, purine or 7-deazapurine moiety. PM is attached to the 3' or the 5&#x2032; position of the sugar moiety when the nucleotide is a deoxyribonucleotide and at the 2&#x2032;, 3&#x2032; or 5&#x2032; position when the nucleotide is a ribonucleotide. BASE is attached to the 1&#x2032; position of SM from the Nposition when BASE is a pyrmidine or the Nposition when BASE is a purine or 7-deazapurine. Sig is covalently attached to PM directly or via a chemical linkage, and represents a detectable moiety covalently attached to SM directly or through a linkage group. Also provided are an oligo- or polynucleotide comprising at least one such phosphate-moiety labeled nucleotide, and other compositions including those wherein a polypeptide is terminally ligated or attached to the oligo- or polynucleotide. The phosphate-moiety labeled nucleotide, and the oligo- or polynucleotides and other compositions comprising such phosphate-moiety labeled nucleotides, are useful as diagnostic tools for detecting analytes and as therapeutic agents.

Oligo- or polynucleotides comprising phosphate-moiety labeled nucleotides

This invention provides in vitro processes for producing copies of specific nucleic acids using protein-nucleic acid constructs which are part of conjugates which are introduced into cells. Illustrative of the elements useful in these constructs for producing copies of specific nucleic acids are promoters, sequences coding for proteins or providing templates for transcription, and RNA polymerases.

Process for producing multiple nucleic acid copies in vivo using a protein-nucleic acid construct

Procedures and compositions for forming and stabilizing non stable branch migrated oligo- and polydeoxynucleotides utilizing a displacer which is either single stranded or partially double stranded and hybridized to a linker strand. The displacer may contain one or more modified nucleotides.

Nucleic acid displacer compositions and cells comprising same

Double hybrid or multihybrid probes and compositions are usefully combined with capture assay and immobilization to provide for detection processes in which target polynucleotides can be detected or the presence or absence of genetic mutations or defects in genetic material can be determined. The capture assay involves capturing a hybrid structure, e.g., single hybrid, double hybrid or multihybrid, or capturing a complex formed by reacting a hybrid structure with a complex forming moiety, e.g., protein, such as a binding protein including an antibody. Immobilization can also be employed prior to hybridization or complexation in which instance a polynucleotide probe can be fixed to a matrix or solid support, e.g., natural or synthetic. Capture and immobilization can be carried out using direct and indirect binding and attachment techniques. Targets can be detected directly or indirectly by using a signal generating moiety and labels.

Processes for detecting polynucleotides, determining genetic mutations or defects in genetic material, separating or isolating nucleic acid of interest from samples, and useful compositions of matter and multihybrid complex compositions

Branch migration of nucleotides

This invention provides methods and compositions for the detection of a target genetic material having a desired base sequence or gene. Also disclosed are methods and compositions for the detection of mutants. The methods and compositions are based in part upon techniques which utilize two labeled single-stranded polynucleotide segments which are complementary to different portions of the genetic material. The methods and compositions of this invention result in the formation of a double hybrid and/or multihybrid, and can furthermore be employed in an attached system, i.e., a matrix-bound entity capable of binding to a polynucleotide probe entity.

Capture sandwich hybridization method and composition

Growing community of inventors

New York, NY, United States of America

Dean L Engelhardt