About
Experienced executive with a demonstrated history of leading successful teams in the…
Articles by Christopher
-
VC-backed Zymeworks strikes optional merger deal with Kairos
VC-backed Zymeworks strikes optional merger deal with Kairos
By Christopher Bond
Activity
-
Friends, I am thrilled to have completed the Timmerman Traverse this year with an all star team of talented and adventurous executives and investors…
Friends, I am thrilled to have completed the Timmerman Traverse this year with an all star team of talented and adventurous executives and investors…
Liked by Christopher Bond
-
Was a great pleasure to attend Posit PBC conf this year. Humbled to be selected to speak and it was great representing ConcertAI. Had a lot of fun…
Was a great pleasure to attend Posit PBC conf this year. Humbled to be selected to speak and it was great representing ConcertAI. Had a lot of fun…
Liked by Christopher Bond
-
Super happy to read the recent Cancer Cell paper from Katy Rezvani lab at MDACC led by Mayra Shanley, PhD "Interleukin-21 engineering enhances NK…
Super happy to read the recent Cancer Cell paper from Katy Rezvani lab at MDACC led by Mayra Shanley, PhD "Interleukin-21 engineering enhances NK…
Liked by Christopher Bond
Experience
Education
Publications
-
A structure-based database of antibody variable domain diversity.
J Mol Biol. 2005 May 6;348(3):699-709.
The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an in vitro-evolved autonomous heavy chain variable domain (V(H)H-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V(H)H-RIG domain at 1.9A resolution and used it to…
The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an in vitro-evolved autonomous heavy chain variable domain (V(H)H-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V(H)H-RIG domain at 1.9A resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through in vitro evolution.
-
AbTrap: Display and Selection of Large Diversity Antibody Libraries in Mammalian Cells
PEGS Boston 2012
In vitro display of antibody libraries has largely relied on display of antibody fragments on phage or fragments and full length antibodies on yeast. Due to limitations of transfection and cell numbers display of large complexity libraries has been limited in eukaryotic hosts. We’ve developed an antibody capture format for display of full length antibodies on mammalian cells. Based on this method we are able to display 1E5-1E6 full length IgG’s per cell. Large diverse collections of antibodies…
In vitro display of antibody libraries has largely relied on display of antibody fragments on phage or fragments and full length antibodies on yeast. Due to limitations of transfection and cell numbers display of large complexity libraries has been limited in eukaryotic hosts. We’ve developed an antibody capture format for display of full length antibodies on mammalian cells. Based on this method we are able to display 1E5-1E6 full length IgG’s per cell. Large diverse collections of antibodies can be displayed in this manner as essentially polyclonal pools. To select and identify individual antibodies within these pools we have developed a protocol encompassing iterative steps of; selection, amplification and deconvolution. In several test examples this process has resulted in the identification of full length IgG clones with affinities in the range of 100pM-10nM.
We’ve developed an antibody capture format for display of full length antibodies on mammalian cells. Based on this method we are able to display 1E5-1E6 full length IgG’s per cell. Large diverse collections of antibodies can be displayed in this manner as essentially polyclonal pools. To select and identify individual antibodies within these pools we have developed a protocol encompassing iterative steps of; selection, amplification and deconvolution. In several test examples this process has resulted in the identification of full length IgG clones with affinities in the range of 100pM-10nM. -
Characterization of residual structure in the thermally denatured state of barnase by simulation and experiment: description of the folding pathway.
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13409-13.
Residual structure in the denatured state of a protein may contain clues about the early events in folding. We have simulated by molecular dynamics the denatured state of barnase, which has been studied by NMR spectroscopy. An ensemble of 10(4) structures was generated after 2 ns of unfolding and following for a further 2 ns. The ensemble was heterogeneous, but there was nonrandom, residual structure with persistent interactions. Helical structure in the C-terminal portion of helix alpha1…
Residual structure in the denatured state of a protein may contain clues about the early events in folding. We have simulated by molecular dynamics the denatured state of barnase, which has been studied by NMR spectroscopy. An ensemble of 10(4) structures was generated after 2 ns of unfolding and following for a further 2 ns. The ensemble was heterogeneous, but there was nonrandom, residual structure with persistent interactions. Helical structure in the C-terminal portion of helix alpha1 (residues 13-17) and in helix alpha2 as well as a turn and nonnative hydrophobic clustering between beta3 and beta4 were observed, consistent with NMR data. In addition, there were tertiary contacts between residues in alpha1 and the C-terminal portion of the beta-sheet. The simulated structures allow the rudimentary NMR data to be fleshed out. The consistency between simulation and experiment inspires confidence in the methods. A description of the folding pathway of barnase from the denatured to the native state can be constructed by combining the simulation with experimental data from phi value analysis and NMR.
-
Cloning, sequence and crystallographic structure of recombinant iron superoxide dismutase from Pseudomonas ovalis.
Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1359-66.
The gene encoding the iron-dependent superoxide dismutase from Pseudomonas ovalis was cloned from a genomic library and sequenced. The ORF differs from the previously published protein sequence, which was used for the original structure determination, at 16 positions. The differences include three additional inserted residues, one deleted residue and 12 point substitutions. The gene was subcloned and the recombinant protein overexpressed, purified and crystallized in a trigonal space group. The…
The gene encoding the iron-dependent superoxide dismutase from Pseudomonas ovalis was cloned from a genomic library and sequenced. The ORF differs from the previously published protein sequence, which was used for the original structure determination, at 16 positions. The differences include three additional inserted residues, one deleted residue and 12 point substitutions. The gene was subcloned and the recombinant protein overexpressed, purified and crystallized in a trigonal space group. The structure was determined by molecular replacement and was refined to 2.1 A resolution.
-
Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains.
J Biol Chem. 2008 Feb 8;283(6):3639-54
We report a comprehensive analysis of sequence features that allow for the production of autonomous human heavy chain variable (V(H)) domains that are stable and soluble in the absence of a light chain partner. Using combinatorial phage-displayed libraries and conventional biophysical methods, we analyzed the entire former light chain interface and the third complementarity determining region (CDR3). Unlike the monomeric variable domains of camelid heavy chain antibodies (V(H)H domains), in…
We report a comprehensive analysis of sequence features that allow for the production of autonomous human heavy chain variable (V(H)) domains that are stable and soluble in the absence of a light chain partner. Using combinatorial phage-displayed libraries and conventional biophysical methods, we analyzed the entire former light chain interface and the third complementarity determining region (CDR3). Unlike the monomeric variable domains of camelid heavy chain antibodies (V(H)H domains), in which autonomous behavior depends on interactions between the hydrophobic former light chain interface and CDR3, we find that the stability of many in vitro evolved V(H) domains is essentially independent of the CDR3 sequence and instead derives from mutations that increase the hydrophilicity of the former light chain interface by replacing exposed hydrophobic residues with structurally compatible hydrophilic substitutions. The engineered domains can be expressed recombinantly at high yield, are predominantly monomeric at high concentrations, unfold reversibly, and are even more thermostable than typical camelid V(H)H domains. Many of the stabilizing mutations are rare in natural V(H) and V(H)H domains and thus could not be predicted by studying natural sequences and structures. The results demonstrate that autonomous V(H) domains with structural properties beyond the scope of natural frameworks can be derived by using non-natural mutations, which differ from those found in camelid V(H)H domains. These findings should enable the development of libraries of synthetic V(H) domains with CDR3 diversities unconstrained by structural demands.
-
Contributions of CDR3 to V H H domain stability and the design of monobody scaffolds for naive antibody libraries.
J Mol Biol. 2003 Sep 19;332(3):643-55.
Camelids produce functional antibodies devoid of light chains. Autonomous heavy chain variable (V(H)H) domains in these molecules have adapted to the absence of the light chain in the following ways: bulky hydrophobic residues replace small aliphatic residues in the former light chain interface, and residues from the third complementarity-determining region (CDR3) pack against the framework and stabilize the global V(H)H domain fold. To determine the specific roles of CDR3 residues in framework…
Camelids produce functional antibodies devoid of light chains. Autonomous heavy chain variable (V(H)H) domains in these molecules have adapted to the absence of the light chain in the following ways: bulky hydrophobic residues replace small aliphatic residues in the former light chain interface, and residues from the third complementarity-determining region (CDR3) pack against the framework and stabilize the global V(H)H domain fold. To determine the specific roles of CDR3 residues in framework stabilization, we used nai;ve phage-displayed libraries, combinatorial alanine-scanning mutagenesis and biophysical characterization of purified proteins. Our results indicate that in the most stable scaffolds, the structural residues in CDR3 reside near the boundaries of the loop and pack against the framework to form a small hydrophobic core. These results allow us to differentiate between structural CDR3 residues that should remain fixed, and CDR3 residues that are tolerant to substitution and can therefore be varied to generate functional diversity within phage-displayed libraries. These methods and insights can be applied to the rapid design of heavy chain scaffolds for the identification of novel ligands using synthetic, antibody-phage libraries. In addition, they shed light on the relationships between CDR3 sequence diversity and the structural stability of the V(H)H domain fold.
-
Determinants of allosteric activation of yeast pyruvate kinase and identification of novel effectors using computational screening.
Biochemistry. 2000 Dec 19;39(50):15333-43.
We have analyzed the structural determinants of the allosteric activation of yeast pyruvate kinase (YPK) by mutational and kinetic analysis and initiated a structure-based design project to identify novel effectors that modulate its allosteric response by binding to the allosteric site for fructose-1,6-bisphosphate (FBP). The wild-type enzyme is strongly activated by fructose-1,6-bisphosphate and weakly activated by both fructose-1-phosphate and fructose-6-phosphate; the strength of the…
We have analyzed the structural determinants of the allosteric activation of yeast pyruvate kinase (YPK) by mutational and kinetic analysis and initiated a structure-based design project to identify novel effectors that modulate its allosteric response by binding to the allosteric site for fructose-1,6-bisphosphate (FBP). The wild-type enzyme is strongly activated by fructose-1,6-bisphosphate and weakly activated by both fructose-1-phosphate and fructose-6-phosphate; the strength of the activation response is proportional to the affinity of the allosteric effector. A point mutation within the 6'-phosphate binding loop of the allosteric site (T403E) abolishes activation of the enzyme by fructose-1, 6-bisphosphate. The mutant enzyme is also not activated by F1P or F6P. The mutation alone (which incorporates a glutamic acid that is strictly conserved in mammalian M1 isozymes) slightly reduces cooperativity of substrate binding. Three novel compounds were identified that effect the allosteric regulation of YPK by FBP and/or act as novel allosteric activators of the enzyme. One is a physiologically important diphospho sugar, while the other two are hydrophobic compounds that are dissimilar to the natural effector. These results demonstrate that novel allosteric effectors may be identified using structure-based screening and are indicative of the potential of this strategy for drug discovery. Regulatory sites are generally more divergent than catalytic sites and therefore offer excellent opportunities for discrimination and specificity between different organisms or between different tissue types.
-
Development of a novel Wnt pathway antagonist antibody, OMP-18R5, that reduces tumor initiating cell frequency in breast cancer
Cancer Research: April 15, 2012; Volume 72, Issue 8, Supplement 1
The Wnt/beta-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several co-receptors, is known to play a critical role in several major cancer types. Mutations in the signalling pathway occur in most cases of human colon cancer, and activation of Wnt signalling through various mechanisms has been reported in multiple major tumor types. We have developed a novel Wnt pathway antagonist antibody, OMP-18R5 which was initially identified by binding to Frizzled7, and…
The Wnt/beta-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several co-receptors, is known to play a critical role in several major cancer types. Mutations in the signalling pathway occur in most cases of human colon cancer, and activation of Wnt signalling through various mechanisms has been reported in multiple major tumor types. We have developed a novel Wnt pathway antagonist antibody, OMP-18R5 which was initially identified by binding to Frizzled7, and subsequently found to also bind several other human FZDs through a conserved epitope within the extracellular domain. OMP-18R5 blocks Wnt binding and canonical signalling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, OMP-18R5 inhibited the growth of a broad range of tumor types and has been found to be particularly active in breast cancer.
-
In vivo evaluation of anti-tumor activity by an anti-VEGF and anti-DLL4 bispecific antibody in a humanized model of skin graft
AACR Annual Meeting 2013
Both Notch/Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) pathways play a critical role in angiogenesis and tumor growth. Due to differential regulatory effects of VEGF and DLL4 on the vasculature, blockage of DLL4 or VEGF inhibits tumor growth by distinct mechanisms: anti-DLL4 treatment induces an abnormal increase of poorly perfused blood vessels, which results in a nonproductive angiogenesis unable to support tumor growth, whereas the anti-VEGF therapy significantly…
Both Notch/Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) pathways play a critical role in angiogenesis and tumor growth. Due to differential regulatory effects of VEGF and DLL4 on the vasculature, blockage of DLL4 or VEGF inhibits tumor growth by distinct mechanisms: anti-DLL4 treatment induces an abnormal increase of poorly perfused blood vessels, which results in a nonproductive angiogenesis unable to support tumor growth, whereas the anti-VEGF therapy significantly decreases vasculature reducing the blood supply to tumors. In our study, we have developed a bispecific monoclonal antibody that targets both human DLL4 (hDLL4) and human VEGF (hVEGF).
-
Phage-display as a tool for quantifying protein stability determinants
Eur J Biochem. 2004 May;271(9):1623-9.
To address questions of protein stability, researchers have increasingly turned to combinatorial approaches that permit the rapid analysis of libraries of protein variants. Phage-display has proved to be a powerful tool for analyzing protein stability due to the large library size and the robustness of the phage particle to a variety of denaturing conditions. With the B1 domain of protein G (GB1) and a camelid heavy chain antibody as model systems, we are using phage-display libraries to…
To address questions of protein stability, researchers have increasingly turned to combinatorial approaches that permit the rapid analysis of libraries of protein variants. Phage-display has proved to be a powerful tool for analyzing protein stability due to the large library size and the robustness of the phage particle to a variety of denaturing conditions. With the B1 domain of protein G (GB1) and a camelid heavy chain antibody as model systems, we are using phage-display libraries to experimentally address questions that have generally been addressed in silico, either through computational studies or statistical analysis of known protein structures. One effort has focused on identifying novel solutions to repacking the hydrophobic core of GB1, while maintaining stability comparable to the wild type protein. In a second study, a small set of substitutions in complimentarity-determining region 3 was found to stabilize the framework of the camelid antibody. Another major focus has been to obtain quantitative data on beta-sheet stability determinants. We have successfully adapted a phage-display method for quantitating affinities of protein variants (shotgun alanine scanning) to analysis of GB1 stability. Using this method, we have analyzed the energetic contributions of cross-strand side chain-side chain interactions. Finally, we discuss parameters to consider in using phage-display to discriminate subtle stability differences among fully folded variants. Overall, this method provides a fast approach for quantitatively addressing biophysical questions.
-
R-Spondin (RSPO) signaling drives the growth of multiple human tumor types
AACR Annual Meeting 2013
The R-spondin-LGR signaling axis is a recently appreciated pathway that promotes beta-catenin signaling in normal stem cell populations. Beta-catenin signaling had long been considered synonymous with Wnt signaling. We conducted a reporter-based screen for secreted beta-catenin signaling activities produced by a panel of human tumors. This exercise and further molecular characterization efforts discovered RSPO activity produced by numerous human tumors of multiple tumor types including ovarian,…
The R-spondin-LGR signaling axis is a recently appreciated pathway that promotes beta-catenin signaling in normal stem cell populations. Beta-catenin signaling had long been considered synonymous with Wnt signaling. We conducted a reporter-based screen for secreted beta-catenin signaling activities produced by a panel of human tumors. This exercise and further molecular characterization efforts discovered RSPO activity produced by numerous human tumors of multiple tumor types including ovarian, pancreatic, colon, breast and non-small cell lung cancer. Specific antibody antagonists of RSPO family members were developed. In minimally passaged human tumor xenograft models, anti-RSPO treatment markedly inhibited tumor growth in several tumor types. Moreover, RPSO blockade promoted tumor differentiation and reduced the frequency of tumor initiating cells. These data highlight the potential for therapeutic intervention with this newly appreciated signaling axis.
-
Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.
Nat Immunol. 2007 Sep;8(9):975-83.
All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable beta-chain 8.2 (V(beta)8.2), each bound to the MHC class II molecule I-A(u), and did energetic mapping of…
All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable beta-chain 8.2 (V(beta)8.2), each bound to the MHC class II molecule I-A(u), and did energetic mapping of V(alpha) and V(beta) contacts with I-A(u). Together with two previously solved structures of V(beta)8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V(beta) loops and the I-A alpha-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.
-
The effects of disulfide bonds on the denatured state of barnase.
Protein Sci. 2000 Dec;9(12):2394-404.
The effects of engineered disulfide bonds on protein stability are poorly understood because they can influence the structure, dynamics, and energetics of both the native and denatured states. To explore the effects of two engineered disulfide bonds on the stability of barnase, we have conducted a combined molecular dynamics and NMR study of the denatured state of the two mutants. As expected, the disulfide bonds constrain the denatured state. However, specific extended beta-sheet structure can…
The effects of engineered disulfide bonds on protein stability are poorly understood because they can influence the structure, dynamics, and energetics of both the native and denatured states. To explore the effects of two engineered disulfide bonds on the stability of barnase, we have conducted a combined molecular dynamics and NMR study of the denatured state of the two mutants. As expected, the disulfide bonds constrain the denatured state. However, specific extended beta-sheet structure can also be detected in one of the mutant proteins. This mutant is also more stable than would be predicted. Our study suggests a possible cause of the very high stability conferred by this disulfide bond: the wild-type denatured ensemble is stabilized by a nonnative hydrophobic cluster, which is constrained from occurring in the mutant due to the formation of secondary structure.
-
Towards a complete description of the structural and dynamic properties of the denatured state of barnase and the role of residual structure in folding.
J Mol Biol. 2000 Mar 10;296(5):1257-82.
The detailed characterization of denatured proteins remains elusive due to their mobility and conformational heterogeneity. NMR studies are beginning to provide clues regarding residual structure in the denatured state but the resulting data are too sparse to be transformed into molecular models using conventional techniques. Molecular dynamics simulations can complement NMR by providing detailed structural information for components of the denatured ensemble. Here, we describe three…
The detailed characterization of denatured proteins remains elusive due to their mobility and conformational heterogeneity. NMR studies are beginning to provide clues regarding residual structure in the denatured state but the resulting data are too sparse to be transformed into molecular models using conventional techniques. Molecular dynamics simulations can complement NMR by providing detailed structural information for components of the denatured ensemble. Here, we describe three independent 4 ns high-temperature molecular dynamics simulations of barnase in water. The simulated denatured state was conformationally heterogeneous with respect to the conformations populated both within a single simulation and between simulations. Nonetheless, there were some persistent interactions that occurred to varying degrees in all simulations and primarily involved the formation of fluid hydrophobic clusters with participating residues changing over time. The region of the beta(3-4) hairpin contained a particularly high degree of such side-chain interactions but it lacked beta-structure in two of the three denatured ensembles: beta(3-4) was the only portion of the beta-structure to contain significant residual structure in the denatured state. The two principal alpha-helices (alpha1 and alpha2) adopted dynamic helical structure.
-
Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors.
Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11717-22
The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft…
The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.
Patents
-
Anti-podocalyxin antibodies and methods of using the same
Filed US WO2017054089 A1
-
VEGF/DLL4 BINDING AGENTS AND USES THEREOF
Issued EU WO2013044215A1
The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are…
The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer
-
Methods for Identifying and Isolating Cells Expressing a Polypeptide
Issued US US20110287979A1
The invention relates to novel polypeptides and cells comprising the polypeptides. The polypeptides and cells are used in methods to identify and/or isolate cells producing a protein with specific biological functions. In particular, the methods may be used for identifying, selecting, and isolating cells producing antigen-specific monoclonal antibodies
-
Variable domain library and uses
Issued US US7785903B2
The invention provides polypeptides comprising a variant heavy chain variable framework domain (VFR). In some embodiments, the amino acids defining the VFR form a loop of an antigen binding pocket. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR. The polypeptide may optionally comprise one or more complementary determining regions (CDRs) of antibody variable domains. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant…
The invention provides polypeptides comprising a variant heavy chain variable framework domain (VFR). In some embodiments, the amino acids defining the VFR form a loop of an antigen binding pocket. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR. The polypeptide may optionally comprise one or more complementary determining regions (CDRs) of antibody variable domains. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR and one or more variant CDRs. Libraries of polypeptides that include a plurality of different antibody variable domains generated by creating diversity in a VFR, and optionally, one or more CDRs are provided and may be used as a source for identifying novel antigen binding polypeptides that can be used therapeutically or as reagents. The invention also provides fusion polypeptides, compositions, and methods for generating and using the polypeptides and libraries
-
Synthetic antibody phage libraries
Issued US US20050079574A1
The invention provides immunoglobulin polypeptides comprising variant amino acids in CDRs of antibody variable domains. In one embodiment, the polypeptide is a variable domain of a monobody and has a variant CDRH3 region. These polypeptides provide a source of great sequence diversity that can be used as a source for identifying novel antigen binding polypeptides. The invention also provides these polypeptides as fusion polypeptides to heterologous polypeptides such as at least a portion of…
The invention provides immunoglobulin polypeptides comprising variant amino acids in CDRs of antibody variable domains. In one embodiment, the polypeptide is a variable domain of a monobody and has a variant CDRH3 region. These polypeptides provide a source of great sequence diversity that can be used as a source for identifying novel antigen binding polypeptides. The invention also provides these polypeptides as fusion polypeptides to heterologous polypeptides such as at least a portion of phage or viral coat proteins, tags and linkers. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided.
-
Met-binding agents and uses thereof
US US 20140286951 A1
The present invention relates to binding agents that specifically bind human MET, binding agents that specifically bind one or more components of the WNT pathway, bispecific agents that bind both human MET and one or more components of the WNT pathway, and methods of using the agents for treating diseases such as cancer.
Other inventors -
RSPO3 Binding Agents and Uses Thereof
US US20140017253 A1
More activity by Christopher
-
Notch created our Top Notch Awards program to support and strengthen Notch Values by recognizing and rewarding employees for outstanding…
Notch created our Top Notch Awards program to support and strengthen Notch Values by recognizing and rewarding employees for outstanding…
Liked by Christopher Bond
-
Congratulations to the investigators at Stanford for the publication of Phase 1 results of autologous CAR22 in Lancet! Lymphoma patients who fail to…
Congratulations to the investigators at Stanford for the publication of Phase 1 results of autologous CAR22 in Lancet! Lymphoma patients who fail to…
Liked by Christopher Bond
-
Pride month is a time to both celebrate individuality and recognize the hurdles that still exist for our #LGBTQIA+ family. ArsenalBio is committed…
Pride month is a time to both celebrate individuality and recognize the hurdles that still exist for our #LGBTQIA+ family. ArsenalBio is committed…
Liked by Christopher Bond
-
We’re embracing and celebrating Pride across our offices always, and especially this summer. There are many upcoming events in our local LGBTQ2S+…
We’re embracing and celebrating Pride across our offices always, and especially this summer. There are many upcoming events in our local LGBTQ2S+…
Liked by Christopher Bond
-
🎉🎉🎉 https://lnkd.in/gS4mmuaE
🎉🎉🎉 https://lnkd.in/gS4mmuaE
Liked by Christopher Bond
-
Honored to be invited third year in a row to talk about the Science of Horror Films at Crypticon Seattle this weekend. https://lnkd.in/ggSZwr-9
Honored to be invited third year in a row to talk about the Science of Horror Films at Crypticon Seattle this weekend. https://lnkd.in/ggSZwr-9
Liked by Christopher Bond
-
From lead TCR discovery to 1st patient dosed in record time. TScan Therapeutics customized multiplex TCR-T therapy for the treatment of solid tumors…
From lead TCR discovery to 1st patient dosed in record time. TScan Therapeutics customized multiplex TCR-T therapy for the treatment of solid tumors…
Liked by Christopher Bond
-
Arsenal Biosciences Announces First Patient Dosed in Clinical Trial for a Treatment for Clear-cell Renal Cell Carcinoma! We at Innovation Ventures…
Arsenal Biosciences Announces First Patient Dosed in Clinical Trial for a Treatment for Clear-cell Renal Cell Carcinoma! We at Innovation Ventures…
Liked by Christopher Bond
-
Happy ASGCT meeting to all attendees. This year I am skipping due to conflicts. But, below is a pic from a talk I gave yesterday talking about…
Happy ASGCT meeting to all attendees. This year I am skipping due to conflicts. But, below is a pic from a talk I gave yesterday talking about…
Liked by Christopher Bond
-
Last week, the entire CARGO team came together to celebrate the opening of our new headquarters in San Carlos, CA! This important milestone signifies…
Last week, the entire CARGO team came together to celebrate the opening of our new headquarters in San Carlos, CA! This important milestone signifies…
Liked by Christopher Bond
Other similar profiles
Explore collaborative articles
We’re unlocking community knowledge in a new way. Experts add insights directly into each article, started with the help of AI.
Explore MoreOthers named Christopher Bond in United States
-
Christopher Bond
-
Christopher Bond
-
Christopher Bond
-
Christopher Bond
PhD Candidate - Johns Hopkins University | NSF I-Corps Entrepreneurial Lead | Organic Electronic Devices
309 others named Christopher Bond in United States are on LinkedIn
See others named Christopher Bond