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NIH Funds Antibody Discovery for Difficult Protein Targets

Chicken on a wooden floor

(A. Kotok, Flickr.

6 Oct. 2023. A biotechnology company is receiving NIH support for discovering antibodies that address the vast majority of proteins coded by the human genome, passed-up so far by drug makers. Integral Molecular in Philadelphia is receiving nearly $900,00 from National Institute of General Medical Sciences or NIGMS, part of National Institutes of Health, for the two-year project.

Integral Molecular discovers and designs monoclonal antibodies, synthetic proteins with immune system properties, as therapies for disease-causing proteins residing on cell membranes, particularly targets considered difficult to reach by conventional means. The company says it specializes in targeting suspected membrane proteins with complex chemistries or well hidden binding sites, called epitopes, and those with rare properties. Integral Molecular offers its antibody discovery technology as a service, and has a pipeline of several antibody candidates in preclinical stages.

The company says it produces monoclonal antibodies by starting with antigen proteins designed to invoke specific responses in protein chemistries. Integral Molecular says it employs virus-like particles and messenger RNA or mRNA in its antigens that create native-like immune responses from cell-membrane proteins. To generate new antibodies, the company says it uses genetically diverse yet humanized engineered chickens as host organisms, whose cells produce varied, but humanized antibody protein responses. Integral Molecular says engineered antibodies from genetically modified chickens are compatible with lab animals for preclinical study as well as humans.

90 percent of proteins not targeted

The award supports NIH’s Illuminating the Druggable Genome initiative, research across multiple NIH institutes and centers to gain a better understanding of the estimated 90 percent of some 4,000 human proteins not targeted by approved drugs. The project focuses on a few collections of these difficult proteins, including G-protein-coupled receptors or GPCRs and ion channels. GPCRs are a large and diverse set of receptor proteins found on cell membranes that play a variety of key functions in the body, with as many as half of all current drugs binding to GPCRs. Ion channel receptors are also evident on some cell membranes, but perform more specialized functions, allowing ion channel pores in the membranes to open or close in response to chemical or mechanical signals. Ion channels are found on excitable cells, such as neurons and in muscles and sensory cells.

To support this initiative, Integral Molecular is discovering engineered monoclonal antibodies addressing 230 GPCRs and ion channels. In a company statement, Ross Chambers, the company’s vice-president for antibody discovery and lead investigator on the project says, with Integral Molecular’s “experience studying complex proteins and an antibody success rate exceeding 95 percent, we are confident in delivering the desired molecules.” Chambers adds, “Our isolation of antibodies reactive with diverse species will help reduce the use of non-human primates in research.”

The award is a Small Business Innovation Research or SBIR grant made under NIH’s small business programs that set aside a part of the agency’s research funding for U.S.-based and owned companies. Most SBIR grants are made in two parts: a first phase to determine technical and commercial feasibility, and a second phase to develop and test a working prototype or prepare for clinical trials. NIH says it allocates $1.3 billion for its small business programs.

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