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The Institute for Protein Innovation (IPI) opened its doors last month on the campus of Harvard Medical School.

Founded by Timothy Springer, Ph.D., Latham Family Professor at Harvard Medical School and Boston Children’s Hospital along with Andrew C. Kruse, Ph.D., Assistant Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, the IPI hopes to bridge the gap between genomes and therapeutics.

The institute’s goals include training the next generation of protein scientists and entrepreneurs, building a large catalog of validated monoclonal antibodies targeting every extracellular protein in humans, making therapeutic leads that can be developed into new drugs, and spawning the formation of new companies. 

In an interview with Drug Discovery & Development, Springer explains what inspired the creation of the Institute for Protein Innovation and his vision for it going forward.

Timothy Springer, Ph.D., Institute for Protein Innovation

DD&D: Why did you choose to focus on protein science?

Springer: Proteins are the targets of all drugs and 50 percent of drugs are actually proteins themselves, and yet, relative to genomics, work on proteins has been remarkably underfunded. In the pharmaceutical industry and biotech there is a huge need for people with experience with proteins but the tools with genomics are so powerful now with DNA and RNA that most biomedical scientists are just DNA jockeys. Proteins are really the next step with genomics and we’re taking the next step with the institute. That’s why I created it.

DD&D: What is the open-source antibody initiative?

Springer: Our antibodies are open source. That means that we are providing the sequences of those antibodies publicly. No company will do that—unless they have to because it’s required in their patent. A huge number of antibodies are sold as research reagents. But companies won’t disclose their sequence because they know if they do other companies will copycat them. It’s our mission to be open source because we think that it’s important for reproducibility and for really being authentic.

DD&D: Why did you make the initiative open source?

Springer: There are two issues we want to address. One is the reproducibility crisis in biological sciences. For example, many antibodies are made by immunizing animals. Each time you immunize an animal you get somewhat different results. Scientists want to use these antibodies in their research but they may not be the same from batch to batch, or worse, they may not have the reactivity that is advertised. So these companies sell these antibodies and list them in their catalogs as being specific for such-and-such protein, but often, they haven’t really validated them—all they’ve done is immunize an animal against a particular peptide but they don’t know if the antibody reacts with that. It’s up to the investigator in many cases to validate that for the company.

Now, the way to make your antibodies totally reproducible is to publish the sequence. That sequence in a public database identifies what that antibody is and uniquely identifies it. There’s the problem nowadays that different antibody providers want to have a complete catalog so many of the antibodies they sell are not made by them. They may change the name of that antibody in their catalog. So if an investigator wants to validate the antibody they’re using, they might buy antibodies from two different manufacturers and get the same result with them. But those two antibodies that have totally different names and identifiers might turn out to actually be the same antibody—and there is no way of tracing that back unless the provider makes the sequence of the antibody known. 

The other reason to be open source is to enable improvement. That concept, in part, stems from computer programming. For example, Linux made their code open source and that means other people can improve on it. So people might actually take our antibody sequences and use them and then make a variation of that sequence and find a higher affinity antibody or an antibody with different or altered specificity. We would then make that available.

DDD: How has the Institute for Protein Innovation evolved since its opening on May 8?

Springer: Initially, we wanted to focus on making antibodies to all extracellular and cell surface proteins and since then we’ve expanded to making the proteins themselves. Andrew Kruse and I are very good at making proteins. That’s the secret sauce. The sequences of all proteins are already known so we will also sell proteins as reagents. That will be a good thing for us to do business wise. We are also adding some new platforms that we weren’t envisioning at first.

DD&D: Why did you choose an academic-entrepreneurial model for the organization?

Springer: I think the academic-entrepreneurial model is really empowering. A nonprofit is friendly with everybody so you can do business with everybody. Plus, we want to be training the next generation of entrepreneurial academics.

The non-profit model is also really good for innovation. For example, there are many companies now that have grant outreach programs to academic institutions—they give some money and help develop the drug in return for a preset royalty amount. But what companies like this are finding is that they don’t get the best stuff. The academics who really know what they’re doing want to start their own company because there’s much more upside for them and much more freedom in the development of their drug.

DD&D: How will Institute for Protein Innovation be a catalyst for training and education?

Springer: “One of the most important and enduring components of the IPI is our commitment to education.  The IPI will create an unparalleled environment for training and teaching the next generation of innovators and entrepreneurs, and will serve as a cross-disciplinary organization to forge productive relationships between academic and industry investigators—which is critical as public funding for scientific education comes under increasing pressure. Neither basic research nor clinical development can exist without the other, and the IPI is building a new model of sustainable collaboration between the non-profit and commercial worlds.”

DD&D: How will commercial industry benefit from this collaboration?

Springer: “Even though we are a nonprofit and through that model can maintain the freedom of an academic enterprise, the IPI will also be a big win for industry. A major focus of our efforts is target discovery. For example, we have a robust platform to "de-orphan" receptors. These are protein receptors whose binding partners are not known. Our technologies will discover those partners. Then, we will make antibodies to them. The result will be a whole new class of drugs that work much more selectively to treat a whole range of diseases with far fewer side effects.”

DD&D: The Institute received initial funding of $5 million from the Massachusetts Life Sciences Center and you donated a $10 million gift. How will the research institute be funded in the future?

Springer: I gave this initial $10 million gift and in 2019 I will put in an additional $15 million dollars. So this $25 million from me plus the $5 million from Massachusetts Life Sciences Center will get us a commitment of $30 million for the first five years. That’s like maybe like a series A plus a Series B for a biotech—that’s pretty good for a startup package. There will be milestones that the institute should achieve after five years, and if those are achieved I will put in more money.

Beyond that, we will be open to philanthropy, and we expect to get grants from institutions like the National Institutes of Health and another grant from Massachusetts Life Sciences Center for other kinds of platforms. We also expect that pharmaceutical and biotech companies will give us money to develop lead therapeutics or tool antibodies for them.

DD&D: What’s next for the Institute of Protein Innovation?

Springer: Let me say one thing about what inspired me to do this in the first place: I trained with César Milstein for my postdoc. He was the inventor of monoclonal antibodies. Despite the promise of genomics, many more drugs have come out of César Milstein’s invention of monoclonal antibodies than have come out of genomics. I’ve spent much of my career working on antibodies and I know the limitations of these species-specific antibodies. There’s a new type of antibody now, a synthetic antibody, that has none of the limitations of species-specific antibodies, and I want to make this available to academic institutions and researchers. I think synthetic antibodies will do for a new generation of researchers what monoclonal antibodies did for me.

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