CHR

IQ Therapeutics has developed a novel proprietary platform technology named “Cloning the Human Response” (CHR) enabling generation of fully human monoclonal antibodies. The starting point is the immune response from patients or volunteers, an effective immune response against a target of interest either based on vaccination or on contraction of a disease. From blood from these donors relevant B-cells are selected and cloned into human cells to produce identical copies of the original human monoclonal antibodies. With suitable assays and donors in place, IQ is able to generate sets of specific fully human antibodies in just a few months time, which can be further screened for efficacy in assays and/or animal models. These antibodies are believed to have optimal properties to fight diseases.

IQ holds worldwide patent families on the CHR technology and on the resulting antibodies.

Antibodies

Antibodies are proteins that help fight bacteria, viruses and cancer. Antibodies can identify and bind to specific pathogens and neutralize them or mark them for attack by the immune system. Thanks to mechanisms developed throughout the course of evolution, the human body is able to generate antibodies against a virtually infinite number of targets. Once a pathogen enters our body, the immune system conducts a high-throughput screen of all the antibodies it can generate (around 10 billion different antibodies), selects a few and improves the target affinity of the selected ones by a process of gene rearrangement and mutation; affinity maturation. After the appropriate antibodies are selected, the B lymphocytes making these selected antibodies turn into production-dedicated plasma cells which secrete large amounts of the selected antibodies into the blood stream "in search" of their specific target. The combination of diversity on the one hand and specificity combined to functionality on the other, makes antibodies a crucial component of our defense mechanism. This combination also makes antibodies a popular platform among scientists and drug companies, which has resulted in a variety of different methods to generate antibodies and especially monoclonal antibodies - antibodies of one particular specificity.

From the human body to the human body

There are many ways, using different methodologies and source materials, to generate monoclonal antibodies. However, it is IQ Therapeutics’ philosophy that the optimal and most physiological entity for the generation, selection and development of antibodies to be used to protect or cure the human body from diseases, is the human body itself. And therefore IQ has focused on developing a technology that utilizes an important part of the human immune response as a physical basis and starting point. IQ has termed this technology "Cloning the Human Response" as it is essentially cloning the antibody-based part of the human immune response.

IQ's Cloning the Human Response technology

The starting point in question consists of affinity matured antibody-producing human B lymphocytes which are derived from blood of well immunized volunteers. The blood is drawn by trained experts under the supervision of a medical practitioner and according to approved Medical Ethics Committee protocol. The human B lymphocytes are separated from the blood and processed according to IQ's technology. At the end, the resulting antibody-producing cells will produce fully human monoclonal antibodies and form an indefinite source. As the antibodies can be used as passive immunity providers which will be effective immediately, "Instant Immunity" can be provided.

Advantages of Instant Immunity antibodies

A major advantage of the CHR technology is that the antibodies resulting from it are fully human. In contrast to humanization techniques, the antibodies will have 100% human sequences, which will permit the development of drug products with a favorable safety profile. Consequently, these antibodies will have reduced immunogenicity as compared to chimeric and humanized antibodies, which reduces the chance of immunologic reactions against the drug products and reduces the chance on adverse reactions. It is likely that these properties also reduce the frequency and amount of dosing. In addition, due to the fact that the antibodies were originally generated inside the human body, the chances that they cross-react with human tissues is reduced. Also, the antibodies have a human glycosylation profile, which is instrumental for optimal efficacy and will limit immunogenicity and adverse reactions. Effector functions of antibodies such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) strongly depend on the carbohydrate moiety (glycosylation) linked to the constant region (fragment crystallizable region = Fc region) of the antibody (see figure 1) and will benefit from the fact that this moiety has a human make-up. Furthermore, in contrast to chimeric and humanized antibodies, IQ’s Instant Immunity antibodies have been selected from the full human potential antibody repertoire and are the result of the human body’s natural affinity maturation process, which is a physiological selection and trial and error system over time leading to antibodies with higher affinities for their targets. This human affinity maturation system generates antibodies with 100 – 1,000 times higher affinity than currently approved chimeric and humanized antibodies. In addition, due to having been generated in the human body and consequently possessing physiological pharmacokinetic and pharmacodynamic properties suitable for the human body, the Instant Immunity antibodies will – upon injection - essentially behave like they originally would have inside the human body.

Figure 1. Schematic representation of antibody.

Therefore, the antibodies originating from IQ’s technology will be of optimal specificity and affinity (typically 10M or better), combined with the best suitable functional and pharmacological properties for the purpose they were generated for in the human body and for the purpose IQ will select them for. In both cases this is a physiological and custom-made protection of the human body against diseases. Another major advantage of providing passive immunity with antibodies is that application will likely be effective in most stages of disease and will also work in most people with reduced immunity (small infants, elderly, and people who are immunocompromised due to disease, immunosuppressive medication, substance abuse etc.). Backed up by molecular cloning techniques to express the genes encoding the antibodies in question in a human production platform of choice, IQ’s Cloning the Human Response human hybridoma technology is a very powerful tool for the development of fully human antibodies.