National Research Council of Canada

Other

University of Windsor

Jamshid Tanha

Saran A Narang

Greg Hussack

Roger MacKenzie

Danica Stanimirovic

Arumugam Muruganandam

Christine M Szymanski

Dae Young Kim

Mehdi Arbabi Ghahroudi

Ali Riazi

Traian Sulea

Wah Yau Wong

Joycelyn Entwistle

Mehdi Arbabi-Ghahroudi

Baomin Tian

Marni Diane Uger

Lakshmi Krishnan

Michael D Dan

Heman Lap Man Chao

Colin Roger Mackenzie

Kevin Henry

Gregory Hussack

Siyaram Pandey

Howard Kaplan

Deyzi Gueorguieva

Ginette Dubuc

Roger Mackenzie

Polypeptides with biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human heavy and light chain variable domains (Vs and Vs), are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human Vs and Vs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human Vs and Vs are also identified. The Vs and Vs identified may be used to create further libraries for identifying additional polypeptides. Further, the Vs and Vs may be subjected to DNA shuffling to select for improved biophysical properties.

Method for isolation of soluble polypeptides

The present document describes an antibody or an antigen-binding fragment that bind to serum albumin comprising three complementarity determining regions (CDR1, CDR2 and CDR3), for half-life extension of biologics. The present invention also relates to pharmaceutical compositions, nucleic acid vectors, cells comprising the nucleic acid vectors, and methods of removing molecules from serum.

Serum albumin binding antibodies for tuneable half-life extension of biologics

A chimeric antigen receptor (CAR) that binds to CEACAM6, an epitope or fragment thereof, or a variant thereof.

CEACAM6 CAR immune cells to treat cancers

Polypeptides with biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human heavy and light chain variable domains (Vs and Vs), are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human Vs and Vs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human Vs and Vs are also identified. The Vs and Vs identified may be used to create further libraries for identifying additional polypeptides. Further, the VS and Vs may be subjected to DNA shuffling to select for improved biophysical properties.

The present invention provides a single domain antibody (sdAb) scaffold comprising one or more than one non-canonical disulfide bond in the framework region (FR). The one or more than one non-canonical disulfide bond may be formed between cysteines introduced by mutations in FR2 and FR3. In the case where the sdAb scaffold is a V, the Cys may be introduced at any one of positions 47-49 and any one of positions 67-71, based on Kabat numbering; in one example, the Cys may be introduced at positions 49 and 69, based on Kabat numbering. In the case where the sdAb scaffold is a V, the Cys residues may be introduced at any one of positions 46-49 and any one of positions 62-66, based on Kabat numbering; in one example, the Cys residues may be introduced at positions 48 and 64, based on Kabat numbering.

Engineering of immunoglobulin domains

is a leading cause of bacterial food-borne diseases in humans, ranging from acute diarrheal disease to neurological disorders. An isolated or purified antibody or fragment thereof specific tois described. The antibody or fragment thereof binds to a flagellar protein and reduces motility of. The antibody or fragment thereof is derived from a heavy chain IgG variable domain fragment (VH) of a camelid animal immunized withflagellar protein. A multivalent form, as well as a phage format, of the antibody or fragment thereof is described. Methods of reducing presence ofin an animal or an animal environment, methods and formulations for treatinginfection, and method of detectingare also described.

Anti-campylobacter jejuni antibodies and uses therefor

Polypeptides with desirable biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human Vs and Vs, are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human Vs and Vs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human Vs and Vs are also identified. The Vs and Vs identified may be used to create further libraries for identifying additional polypeptides. Further, the Vs and Vs may be subjected to DNA shuffling to select for improved biophysical properties.

The present invention is directed totoxin-specific antibodies, compositions, and uses thereof. The anti-toxin antibodies may be specific for either TcdA or TcdB. The invention also includes methods of treating ainfection, methods of capturingtoxins, and methods of detectingtoxins.

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The present invention provides a single domain antibody (sdAb) scaffold comprising one or more than one non-canonical disulfide bond in the framework region (FR). The one or more than one non-canonical disulfide bond may be formed between cysteines introduced by mutations in FR2 and FR3. In the case where the sdAb scaffold is a V, the Cys may be introduced at any one of positions (47-49) and any one of positions (67-71), based on Kabat numbering; in one example, the Cys may be introduced at positions (49) and (69), based on Kabat numbering. In the case where the sdAb scaffold is a V, the Cys residues may be introduced at any one of positions 46-49 and any one of positions (62-66), based on Kabat numbering; in one example, the Cys residues may be introduced at positions (48 and 64), based on Kabat numbering.

A phage-displayed library of llama single heavy domain antibodies (sdAbs) was enriched for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). From the enriched library, two sdAbs were selected, sequenced, subcloned, and expressed as fusion proteins with c-myc-Histags (Hisis SEQ ID NO:101). Similarly as phage-displayed sdAbs, these soluble tagged sdAbs were shown to selectively bind to HCEC and to transmigrate across in vitro human blood-brain barrier (BBB) model. In contrast to an unrelated llama sdAb, these sdAbs were also detected in the brain after i.v. injection into mice. These small (&#x2dc;13 kDa) antibody fragments have essential characteristics of brain-specific delivery vectors and can be used to facilitate drug transport across the BBB.

Single domain brain-targeting antibody fragments derived from llama antibodies

Phage display libraries are taught in which the recombinant phage population displays a plurality of potential binding fragments having preferred characteristics of solubility and/or intermolecular interaction. Also taught are methods of biasing display libraries to produce variants which more closely approximate the preferred characteristics of the parental binding fragment.

Single-domain anti-bodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the active of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and/or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins.

Anti-apoptotic protein antibodies

Polypeptides with desirable biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human VHs and VLs, are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human VHs and VLs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human VHs and VLs are also identified. The VHs and VLs identified may be used to create further libraries for identifying additional polypeptides. Further, the VHs and VLs may be subjected to DNA shuffling to select for improved biophysical properties.

Growing community of inventors

Ottawa, Canada

Jamshid Tanha