Proyecto Apperitivo

Hoy en día, si uno desea piqueos artesanales debe prepararlos uno mismo o comprarlos de manera independiente en proveedores distintos, lo que resulta en un proceso largo y tedioso. Asimismo, para aquellas empresas que venden piqueos, que en su mayoría son pequeñas, se evidencia una dificultad para hacer crecer y expandir su negocio, pues invertir en un local es costoso e ingresar a aplicaciones de delivery reconocidas representa un gasto elevado. Es así como surge Apperitivo, una aplicación en la cual las personas pueden encontrar una gran variedad de piqueos de distintos proveedores en una sola plataforma y por delivery. Las empresas de piqueos, por su parte, se pueden unir a cambio del pago de una comisión sobre la venta. Para poder validar el modelo de negocio propuesto, se realizaron diferentes experimentos, que abarcaron desde el diseño de prototipos de la app, entrevistas con expertos, programadores, empresas de piqueos, consumidores potenciales, entre otros; así como se empleó el método concierge, para la validación de la fuente de ingresos a través de la venta en redes sociales. Esto permitió validar la factibilidad y atractivo de la aplicación. Además, se elaboró el plan de negocios de Apperitivo, incluyendo aspectos importantes relacionados al marketing, operaciones, recursos humanos, RSE y finanzas, lo que permitió proyectar el negocio, determinar su escalabilidad y rentabilidad. Finalmente, todo lo anterior apunta a que Apperitivo es un negocio viable, atractivo e innovador, que responde a una necesidad real.Nowadays, if a person wants artisanal snacks, he has to prepare them himself or buy them independently from different suppliers, which results in a long and tedious process. Likewise, for those companies that sell snacks, which are mostly small, it is difficult to grow and expand their business, since investing in a store is expensive, and entering recognized delivery applications represents a high expense. This is how Apperitivo arises, an application in which people can find a wide variety of snacks from different providers on a single platform and by delivery. In addition, snacks companies can join the app in exchange for the payment of a commission on the sale. To validate the proposed business model, different experiments were carried out, ranging from the design of application prototypes to interviews with experts, programmers, snack companies, potential consumers, among others; as well as the concierge method was used to validate the source of income through the sale on social networks. This succeeded in validating the feasibility and attractiveness of the application. Besides, Apperitivo's business plan was prepared, including important aspects related to marketing, operations, human resources, CSR and finances, which made it possible to project the business, and determine its scalability and profitability. Finally, all the analysis done indicates that Apperitivo is a viable, attractive, and innovative business that responds to a real need.Trabajo de investigació

Protective anti‐prion antibodies in human immunoglobulin repertoires

Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified > 6,000 PrP‐binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage‐derived antibodies. When expressed recombinantly, these antibodies exhibited anti‐PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti‐PrP IgGs and found 21 high‐titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti‐PrP autoimmunity is innocuous. The existence of anti‐prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease‐associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations

Antibody complementarity determining region design using high-capacity machine learning

MOTIVATION: The precise targeting of antibodies and other protein therapeutics is required for their proper function and the elimination of deleterious off-target effects. Often the molecular structure of a therapeutic target is unknown and randomized methods are used to design antibodies without a model that relates antibody sequence to desired properties. RESULTS: Here, we present Ens-Grad, a machine learning method that can design complementarity determining regions of human Immunoglobulin G antibodies with target affinities that are superior to candidates derived from phage display panning experiments. We also demonstrate that machine learning can improve target specificity by the modular composition of models from different experimental campaigns, enabling a new integrative approach to improving target specificity. Our results suggest a new path for the discovery of therapeutic molecules by demonstrating that predictive and differentiable models of antibody binding can be learned from high-throughput experimental data without the need for target structural data. AVAILABILITY AND IMPLEMENTATION: Sequencing data of the phage panning experiment are deposited at NIH's Sequence Read Archive (SRA) under the accession number SRP158510. We make our code available at https://github.com/gifford-lab/antibody-2019. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Protective anti‐prion antibodies in human immunoglobulin repertoires

Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified > 6,000 PrP‐binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage‐derived antibodies. When expressed recombinantly, these antibodies exhibited anti‐PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti‐PrP IgGs and found 21 high‐titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti‐PrP autoimmunity is innocuous. The existence of anti‐prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease‐associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations

Protective anti‐prion antibodies in human immunoglobulin repertoires

Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified > 6,000 PrP‐binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage‐derived antibodies. When expressed recombinantly, these antibodies exhibited anti‐PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti‐PrP IgGs and found 21 high‐titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti‐PrP autoimmunity is innocuous. The existence of anti‐prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease‐associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations

MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans

A large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. We generated a fully human antibody (MAA868) that binds the catalytic domain of both FXI (zymogen) and activated FXI. Our structural studies show that MAA868 traps FXI and activated FXI in an inactive, zymogen-like conformation, explaining its equally high binding affinity for both forms of the enzyme. This binding mode allows the enzyme to be neutralized before entering the coagulation process, revealing a particularly attractive anticoagulant profile of the antibody. MAA868 exhibited favorable anticoagulant activity in mice with a dose-dependent protection from carotid occlusion in a ferric chloride-induced thrombosis model. MAA868 also caused robust and sustained anticoagulant activity in cynomolgus monkeys as assessed by activated partial thromboplastin time without any evidence of bleeding. Based on these preclinical findings, we conducted a first-in-human study in healthy subjects and showed that single subcutaneous doses of MAA868 were safe and well tolerated. MAA868 resulted in dose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time and FXI suppression for up to 4 weeks or longer, supporting further clinical investigation as a potential once-monthly subcutaneous anticoagulant therapy