Advanced Proteome Therapeutics this week said it is looking to forge partnerships with companies that can help it develop a technology designed to boost the efficacy of protein therapeutics without making them toxic.
Earlier this month, the company said it has developed methods to attach molecules to human growth hormone on a site-selective manner, a “milestone” that suggests a general method for protein modification and site-specific labeling, potentially resulting in improved protein therapeutics.
Targeting a protein-diagnostic and -therapeutic market that APT estimates will reach $50 billion by 2010, the company hopes its technology, called protein-site targeting, will be used to improve existing protein therapeutics as well as those in development.
Although several protein therapeutics are on the market, they are “suboptimal” in vivo in terms of the length of their biological activity, solubility, and other properties, APT CEO Alexander Krantz told ProteoMonitor this week.
With an eye to improving these drugs, researchers have created a number of methods to modify the proteins, including crosslinking them, fusing them to other proteins, and especially linking proteins to a polymer such as polyethylene glycol, a process known as PEGylation, that has been shown to be effective in improving the potency, in vivo half-life, and patient tolerance.
However, Krantz, who is also the founder and president of APT, said that most of these techniques mutate the protein and result in heterogeneous mixtures that would not be approved by the US Food and Drug Administration.
“In some exceptional instances by exploiting certain types of chemical principle, you can get something site-specifically labeled. But generally, there’s really no generic technology to do this,” Krantz said.
Krantz, who has been working in site-specific labeling for 30 years, said that the technology he has developed allows molecules to bind to proteins without changing the protein’s sequence, eliminating the danger of potential toxicity and other side effects from the modified therapeutic.
ATP’s technology consists of ensembles of proprietary molecules and novel assays. The molecules in the ensembles are of different shapes attached to a constant reactive component. Each ensemble is made up of molecules containing an inert affinity group and a labeling affinity.
According to Krantz, “It is the affinity group which gives each particle its distinctive shape and serves as a homing device for complementary sites on the protein surface,” while the labeling affinity functions as the glue to attach the desired group to the protein surface.
“We’re a redevelopment company even more so than a development company because our goals are really on protein therapies that are established products but are suboptimal, and we want to make them much better.”
“The notion is that we would make up this collection of shapes,” Krantz said. “And we would mix the protein, or contact the protein with them, and then we would look for signals that signify that essentially these things have landed. And … we basically do it by kinetic measurement or rate measurement.”
Because the technology is a general method that allows researchers to attach molecules to proteins without mutating the protein, “you can attach lots of things by our technology. You can attach anything, in principle,” Krantz said.
APT has tested the ability of its technology to bind to proteins on chemicals such as polyethylene glycol, polymers, and “things that are known to increase binding to human serum albumin.”
Earlier this month, the company said that its technology had reached a milestone when it successfully applied it to a group of proteins that have proven especially tricky for drug makers to work with — proteins that bind preferentially to other proteins and large molecules.
“In the pharmaceutical industry it’s been exceedingly difficult to make small molecule-linked drugs toward these proteins,” Krantz said. “If you give [the protein target] something small, you don’t see very high affinity.
“There really are no small molecules known for some of these things that will bind with affinity to them. Yet we were able to discover things that are small enough that you can almost mimic with small-molecule drugs in a development program,” he said.
The company has not published its data, but is preparing to do so, Krantz said. The firm has also filed applications for the technology with the US Patent and Trademark Office and the World Intellectual Property Organization.
Next, Protein Biochips
Founded in 2003, APT is headquartered in Vancouver, British Columbia, though all its R&D is done out of its Boston site, where Krantz is based. The company, which has four employees, trades on the Canadian Stock Exchange under the ticker symbol APC.
According to documents filed with Canadian regulators, APT posted revenues of $34,061 for its fiscal second quarter, which ended Jan. 31, up 54 percent from $22,089 recorded in the year-ago period. Net loss during the quarter totaled $359,236, a 217-percent increase from $113,252 year over year. The company said it had $2.9 million in cash and cash equivalents as of Jan. 31.
APT said it is now seeking collaborations with therapeutics firms. In November, it inked an R&D deal with Atreus Pharmaceuticals to develop novel protein in vivo imaging agents with the aim of viewing the earliest changes associated with rheumatoid arthritis.
Atreus has the exclusive rights to commercialize jointly developed agents, while APT would receive payments in return. Atreus is providing technical, clinical, market expertise, and intellectual properties to the deal. Financial terms of the deal were not disclosed
The technology can be used for new protein-therapeutics development, but APT said it is more interested in improving therapies already on the market.
“We’re very, very eager to get our hands on proteins that people are excited to modify and show that we can do that effectively,” Krantz said. “We’re a redevelopment company even more so than a development company because our goals are really on protein therapies that are established products but are suboptimal, and we want to make them much better.”
The company is also in the early stages of developing protein biochips. While gene biochips are standard tools in genomic research, protein chips have only been around since 2000 when a team of Purdue University researchers spotted proteins onto silicon chips.
But creating protein chips remains a difficult process because “you don’t want the protein in a lot of orientations, because you really don’t know what it’s doing when it’s in different shapes and orientations,” Krantz said.
While various protein-chip technologies exist, attaching protein mixtures to single points of attachment remains a technical challenge, Krantz said.
In preliminary work, APT has developed a chemical system that Krantz said allows “a large number of proteins selectively at one point of the attachment, which would usually be the N-terminal.”
The company is in the process of optimizing the technology, he said.