EMERYVILLE, CA, United States
EMERYVILLE, CA, United States
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Patent
Crystal Bioscience, Inc. | Date: 2016-12-13

A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.


Patent
Crystal Bioscience, Inc. | Date: 2016-05-27

A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immunoglobulin gene is provided, as well as cells and targeting vectors for making the same.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.81M | Year: 2012

DESCRIPTION (provided by applicant): Approximately 25% of the products being developed by the biotechnology industry are antibodies and many of these antibodies are directed to epitopes on human cells and tissues. We are proposing a novel concept for the production of antibodies with therapeutic potential that is based on recent advances in protein-protein interactions and recent developments in transgenic technology. Execution of this concept will obviate many of the expensive and time consuming modifications that are frequently required after potentially therapeutic monoclonal antibodies are identified in order to optimize their pharmacological properties and to make them amenable to large scale production. By combining recent data derived from in vitro studies with the nascent understanding of genomics, we will extend the range of epitopes that can be accessed and, therefore, extend the range of potentially therapeutic antibodies. PUBLIC HEALTH RELEVANCE: During the past 15 years, more than 20 therapeutic antibodies have been developed to treat human disease, particularly in the fields of autoimmunity and cancer. We have proposed a novel method to obtain potentially therapeutic antibodies that will recognize targets that cannot be obtained from conventional sources. In addition, the technology will engineer antibodies that have improved pharmacological attributes and better manufacturing properties. This technology will provide a cost-effective route to increasing the range of therapeutic candidatesfor the treatment of human disease.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 194.78K | Year: 2012

DESCRIPTION (provided by applicant): We seek to capitalize on a substantial body of work has characterized the immune responses of HIV+ individuals with very slow disease progression (LTNP), and HIV- individuals who do not seroconvert despite repeated HIVexposure (ESN). A fraction of people in these groups produce natural anti-CCR5 antibodies that are associated with their disease-free status (in longitudinal studies loss of these antibodies results in disease progression). These antibodies are unique in that they bind a rare CCR5 epitope, induce a long term downregulation of CCR5 on the surface of cells, and can inhibit transcytosis of HIV across mucosal membranes. Experimentally raised polyclonal chicken antibodies to this epitope are even more potent than their human-derived counterparts with respect to these biological activities, and represent an opportunity to develop a unique product offering in the HIV/AIDS arena. We will use our proprietary technology to raise a panel of chicken monoclonal antibodies to this CCR5 epitope and humanize the most active members of this panel for further development. PUBLIC HEALTH RELEVANCE: An estimated 33.4 million people worldwide are now living with HIV, and 2.7 million are newly infected every year, with a higher prevalence among women, as women are biologically more vulnerable to HIV than men. Anti-viral drugs have proven effective in allowing HIV+ individuals to live longer disease-free lives. However, this success has done little to reduce the spread of HIV/AIDS worldwide, since it does not address HIV transmission between individuals. In principle, vaccines can solve this problem, although many years of intense effort have not yielded a product. The difficulty is to some extent due to the ability of HIV, more so than other viruses, to rapidly evolve and therefore evade a vaccine-centric immune response that is restricted by the physical structure of the vaccine itself. Furthermore, it is well known that HIV+ individuals produce antibodies to viral proteins,but generally these antibodies do not slow the progression of disease. For these reasons, a new strategy has emerged: to identify blocking antibodies against the HIV receptors or co-receptors, such as CCR5, rather than the virus itself. The receptors/co-receptors are native human proteins that HIV requires, but does not genetically control. However, since receptors are self proteins, it is unlikely that a vaccine approach will reliably generate a vigorous response in humans. The alternative is to develop potent antibodies independently in other species, and use humanized versions of them in the modality of passive immunotherapy. Antibodies that block HIV infection could potentially be used therapeutically in HIV+ individuals to reduce viral load and disease progression, and could also be used prophylactic ally to reduce transmission between individuals if present in the appropriate mucosal tissues. An innovative approach using a humanized chicken monoclonal antibody to a cryptic epitope on the HIV co- receptor CCR5 is anticipated to yield a candidate that is superior to other CCR5 antibodies in preclinical or clinicl development.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 216.90K | Year: 2016

DESCRIPTION provided by applicant We seek to capitalize on a substantial body of work that has characterized the immune responses of HIV individuals with very slow disease progression LTNP and HIV individuals who do not seroconvert despite repeated HIV exposure ESN A fraction of people in these groups produce natural anti CCR antibodies that are associated with their disease free status in longitudinal studies loss of these antibodies results in disease progression These antibodies are unique in that they bind rare CCR epitopes induce a long term downregulation of CCR on the surface of cells and can inhibit transcytosis of HIV across mucosal membranes Experimentally raised polyclonal chicken antibodies to these epitopes are even more potent than their human derived counterparts with respect to these biological activities and represent an opportunity to develop a unique product offering in the HIV AIDS arena We will use our proprietary technology to raise a panel of chicken monoclonal antibodies to these CCR epitopes and humanize the most active members of this panel for further development PUBLIC HEALTH RELEVANCE An estimated million people worldwide are now living with HIV and million are newly infected every year with a higher prevalence among women in developing countries Anti viral drugs have proven effective in allowing HIV individuals to live longer disease free lives However this success has done little to reduce the spread of HIV AIDS worldwide since it does not address HIV transmission between individuals In principle vaccines can solve this problem although many years of intense effort have not yielded a product The difficulty is to some extent due to the ability of HIV more so than other viruses to rapidly evolve and therefore evade a vaccine centric immune response that is restricted by the physical structure of the vaccine itself Furthermore it is well known that HIV individuals produce antibodies to viral proteins but generally these antibodies do not slow the progression of disease For these reasons a new strategy has emerged to identify blocking antibodies against the HIV receptors or co receptors such as CCR rather than the virus itself The receptors co receptors are native human proteins that HIV requires but does not genetically control However since receptors are andquot selfandquot proteins it is unlikely that a vaccine approach will reliably generate a vigorous response in humans The alternative is to develop potent antibodies independently in other species and use humanized versions of them in the modality of passive immunotherapy Antibodies that block HIV infection could potentially be used therapeutically in HIV individuals to reduce viral load and disease progression and could also be used prophylactically to reduce transmission between individuals if present in the appropriate mucosal tissues An innovative approach using a humanized chicken monoclonal antibody to a cryptic epitope on the HIV co receptor CCR is anticipated to yield a candidate that is superior to other CCR antibodies in preclinical or clinical development


Patent
Crystal Bioscience, Inc. | Date: 2012-05-23

A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immuno -well as globulin gene is provided, as we cells and targeting vectors for making the same.


Patent
Crystal Bioscience, Inc. | Date: 2014-09-16

A sustained culture of isolated avian gonocytes is provided, as well as a method of making and using the same. A chimeric avian containing an isolated gonocyte and a transgenic avian produced using the chimeric avian are also provided. The cell and method may be employed to make, among other things, transgenic avian that produce a heterologous protein, e.g., a therapeutic protein.


Patent
Crystal Bioscience, Inc. | Date: 2016-06-21

A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.


Patent
Crystal Bioscience, Inc. | Date: 2016-06-08

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.


Patent
Crystal Bioscience, Inc. | Date: 2013-10-18

A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.

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