Large Scale Biology Corporation

Kentucky Bioprocessing, Inc.

The Dow Chemical Company

Schering-Plough Animal Health Corporation

Biolex Therapeutics, Inc.

Indian Council of Medical Research

Gregory P Pogue

John A Lindbo

Thomas H Turpen

Stephen J Garger

Michael J McCulloch

Wayne P Fitzmaurice

Kenneth E Palmer

Jonathan E Lawrence

Cynthia S Gross

Mark L Smith

Mark D Cochran

Ignacio Mario Larrinua

Laurence K Grill

Monto H Kumagai

David E Junker

Hal S Padgett

Avutu Sambi Reddy

Daniel Gachotte

Guy R Della-Cioppa

Philip J Savickas

Robert L Erwin

Stephen J Reinl

Randy J Pell

Max Otto Ruegger

Barbara A Miller

Poonam Salotra

Beth Blakeslee

David A McCrery

J Vincent B Oriedo

Rodney Crosley

Long V Nguyen

Alison A McCormick

Hiralal Nakhasi

Steven P Holzberg

Ted Weglarz

Wenjin Zheng

Gerson Wolfe

Gannavaran Sreenivas

Herein-described are various methods for making a vaccine that are made of re-assembled virus like particles (VLP). First, the VLPs are disassembled into encapsidation intermediate populations. Each encapsidation intermediate population undergoes, for instance, chemical conjugation of unique peptide or nucleic moieties to form separate populations. Thereafter, a predetermined amount of each of the several (one or more) different encapsidation intermediates from the different populations is mixed and joined, forming intact VLPs, surrounding a nucleic acid core, that are composed of different encapsidation intermediate such that the reassembled VLP displays more than one peptide or nucleic acid. The nucleic acid can function either as a scaffold alone or can be engineered for the expression of an immunomodulatory protein in a eukaryotic cell.

Flexible vaccine assembly and vaccine delivery platform

The invention described herein provides a C-terminally truncated interferon having a deletion of 7, 8, or 9 amino acids and having enhanced biological activity, and the polynucleotides encoding such an interferon. Also provided are methods for producing and using such truncated interferon. In some embodiments, the truncated interferon is produced in a plant.

C-terminally truncated interferon

The invention provides a fusion protein comprising a plant virus coat protein and a GDF8 peptide domain, or antigenic fragment of the GDF8 peptide domain. Plant virus vectors expressing the fusion protein and methods of using these vectors are also provided.

Plant virus coat fusion proteins with GDF8 epitopes and vaccines thereof

The present invention relates to foreign peptide sequences fused to recombinant plant viral structural proteins and a method of their production. Fusion proteins are economically synthesized in plants at high levels by biologically contained tobamoviruses. The fusion proteins of the invention have are useful as antigens for inducing the production of antibodies having desired binding properties, e.g., protective antibodies, or for use as vaccine antigens for the induction of protective immunity against the parvovirus. Feline parvovirus epitopes were fused to the N-terminus of the TMV coat protein, expressed inplants, extracted, purified, characterized and administered to animals, resulting in protective immunity.

Production of a parvovirus vaccine in plants as viral coat protein fusions

This invention relates to putative known and unknown deoxyribonucleic acid (DNA) and amino acid sequences identified in one or more metabolic pathways that lead to dwarfism and stunting in plants and the use of these sequences in agriculture to create dwarf varieties of any plant species. This invention also relates to nucleic acids sequences and polypeptides that produce altered metabolism phenotypes in plants.

Nucleic acids compositions conferring dwarfing phenotype

The present invention provides nucleic acid sequences having an altered viral movement protein and 126/183 kDa replicase proteins further characterized in its ability tostabilize a transgene contained in a virus that expresses the altered movement protein. The present invention also provides viral vectors expressing the altered movement protein, cells transformed with the vectors, and host plants infected by the viral vectors.

Viral expression vectors

A rolling circle DNA replicon which replicates in a host eukaryotic cell is disclosed which has a truncated replication cycle. The rolling circle DNA replicon comprises the following elements present on the same DNA molecule. It contains a Rep gene open reading frame from a virus belonging to the viral taxonomic families Geminiviridae, Circoviridae or genus Nanovirus. The Rep gene open reading frame is placed under transcriptional control of a promoter, which is placed 5' of the gene. Any sequences that are required to be present in cis on the rolling circle DNA replicon in order that the Rep protein might promote replication of the rolling circle DNA replicon are included. An expression cassette for expression of an ancillary protein that is capable of creating a cellular environment permissive for replication of the rolling circle DNA replicon in the host cell of interest is also included. At least one expression cassette with an RNA polymerase II promoter, a multiple cloning site, and transcription termination and polyadenylation signals suitable for transcription of RNA molecules not normally intrinsic to a geminiviral, circoviral or nanoviral genome is also included.

Rolling circle replicon expression vector

The present invention relates to a polymerase chain reaction (PCR) assay for the diagnosis of leishmaniasis using specific oligonucleotide primers for the identification ofparasites in clinical samples.

Species-specific PCR assay for detection of Leishmania donovani in clinical samples of kala-azar and post kala-azar dermal leishmaniasis

The invention relates to the production of enzymatically active recombinant human and animal lysosomal enzymes involving construction and expression of recombinant expression constructs comprising coding sequences of human or animal lysosomal enzymes in a plant expression system. The plant expression system provides for post-translational modification and processing to produce a recombinant gene product exhibiting enzymatic activity. The invention is demonstrated by working examples in which transgenic tobacco plants express recombinant expression constructs comprising human glucocerebrosidase nucleotide sequences. The invention is also demonstrated by working examples in which transfected tobacco plants express recombinant viral expression constructs comprising human &#x3b1; galactosidase nucleotide sequences. The recombinant lysosomal enzymes produced in accordance with the invention may be used for a variety of purposes, including but not limited to enzyme replacement therapy for the therapeutic treatment of human and animal lysosomal storage diseases.

Production of lysosomal enzymes in plants by transient expression

The present invention relates to recombinant viral vectors encoding a transcriptional unit, that encodes a fusion protein, or a foreign protein or a gene of interest to be silenced, which can be expressed in a host. The present invention also relates to the use of these recombinant viral vectors to express a fusion protein, a foreign protein, to silence a gene of interest in a host. The present invention also relates to the use of these recombinant viral vectors to screen a CDNA or genomic library in order to correlate a nucleotide sequence with a phenotypic or biochemical change.

Cytoplasmic inhibition of gene expression and expression of a foreign protein in a monocot plant by a plant viral vector

The present invention relates to foreign peptide sequences fused to recombinant plant viral structural proteins and a method of their production. Fusion proteins are economically synthesized in plants at high levels by biologically contained tobamoviruses. The fusion proteins of the invention have are useful as antigens for inducing the production of antibodies having desired binding properties, e.g., protective antibodies, or for use as vaccine antigens for the induction of protective immunity against the parvovirus. Feline parvovirus epitopes were fused to the N-terminus of the TMV coat protein, expressed in Nicotiana plants, extracted, purified, characterized and administered to animals, resulting in protective immunity.

Parvovirus vaccine as viral coat protein fusions

The present invention provides nucleic acid sequences having an altered viral movement protein and 126/183 kDa replicase proteins further characterized in its ability to stabilize a transgene contained in a virus that expresses the altered movement protein. The present invention also provides viral vectors expressing the altered movement protein, cells transformed with the vectors, and host plants infected by the viral vectors.

The present invention relates to a method for using viral vectors to bear populations of sequence variants and using plant hosts to select the sequences that exhibit the desired traits.

Method for expressing a library of nucleic acid sequence variants and selecting desired traits

This invention is directed to a plus strand RNA viral vector for transformation of a host organism with a foreign RNA, and expression of said foreign RNA. The foreign RNA is inserted into an infective RNA viral segment containing cis-acting viral replication elements, and allowed to infect the host organism. The RNA vector is modified to obtain infectivity by including an intervening sequence between the cap and the 5&prime; end. The modified RNA is able to tolerate the exogeneous RNA segment without disrupting the replication of the modified RNA, in the absence of a trans-acting viral replication element in a single component plant virus host cell.

RNA transformation vectors derived from a single-component RNA virus and contain an intervening sequence between the cap and the 5&prime; end

Growing community of inventors

Vacaville, CA, United States of America

Gregory P Pogue