[Disclosure: AgFunderNews’ parent company AgFunder is an investor in Alpine Bio.]
Nobell Foods—a molecular farming startup engineering plants to produce animal proteins in what it claims is a more sustainable and ultimately more efficient manner—has secured its 10th US patent* and rebranded as Alpine Bio.
Founded by Magi Richani in 2016 as Alpine Roads, the San Francisco-based company still plans to launch cheeses featuring its animal-free casein under the Nobell Foods brand, but says it now has a far broader remit, with work progressing on up to 15 proteins that can be expressed in a variety of plants.
“We ended up building a massive database and IP portfolio covering ways to produce recombinant proteins in plants, and while Nobell Foods makes sense as a consumer brand, it is not enough to convey the power of our platform,” said Richani, a civil engineer who built a career at oil giant Shell in project management before setting up her own business.
“In the short term,” she told AgFunderNews, “our focus is on bringing cheese to market through the Nobell brand, but at the end of the day, the goal is to have the biggest impact, which means making plant-derived casein accessible to everybody [as Alpine Bio].”
Molecular farming vs precision fermentation
Microbes can be engineered to produce casein protein via prevision fermentation. However, a molecular farming approach can be scaled at a fraction of the cost thanks to lower CapEx and operational costs and the ability to tap into existing infrastructure, claimed Richani, who says most plant-based cheeses miss the mark because of how challenging it is to replicate the qualities of casein, the dairy protein that makes cheese melt and stretch.
And while microbes can only make individual casein proteins (there are four types: alpha S-1, alpha S-2, beta, and kappa), plants can be engineered to make two or more at a time, she noted.
In simple terms, Alpine Bio is genetically engineering soybeans—which already have the capability to produce large amounts of protein—to produce casein proteins by inserting DNA sequences originally from cows into the genome of the plant.
However, because there are proteases (enzymes) in the plant that break down casein, it has also had to develop techniques to prevent this from happening, explained Richani.
“We tried all these strategies over the years to increase the accumulation of the casein proteins in the plant, but also to shield it from these proteases with other proteins, as if you express more than one casein protein or express casein and a whey protein like beta lactoglobulin in the same plant, they seem to protect each other.”
IP: ‘Our claims are pretty broad’
While Alpine Bio can produce soybeans containing all four casein proteins (in cow’s milk, they fold up into a spherical ‘micelle’ structure in which the proteins are suspended in a solution along with calcium and other minerals) this is not strictly necessary, said Richani.
“There’s no technical limitation on making all of them at once; the question is, does that get you the best product? We have done a lot of work on isolating individual caseins, understanding their functionalities independently and in different combinations, and we’re currently looking at producing two of them together.”
The firm’s latest patent covers “not just making these proteins, but their use in food formulations,” she said. “So we have claims that cover not just how we make the proteins, but how we use them, so that if for whatever reason someone gets around the production piece, we have really robust composition claims.”
She added: “We have been developing this technology since 2016 and we have accumulated a lot of IP, so our portfolio is very robust, meaning anyone making these proteins in plants is going to have to deal with our IP portfolio at some point. And we’re not just talking about soybeans, but any plant system producing casein, so our claims are pretty broad.”
Which plants make the most sense as casein production vehicles?
So why pick soybeans?
“At the end of the day, we chose soy because we believe it gives us the best chances of competing on economics with commodity priced animal proteins,” said Richani.
“Soy is a commodity crop that has been optimized for maximizing protein with on average 35% protein by weight, plus there are about 90 million acres grown per year in the US, so that’s a lot of farmers we can work with plus a huge infrastructure for processing soybeans, both for removing the oil and processing the [solid matter] into purified ingredients like protein isolates.”
While it may be easier to extract protein from lettuce or potatoes, she said, they don’t produce as much protein.
What level of purity is needed?
Oil from the modified beans is highly refined, and will not have traces of dairy protein, but the soy protein stream from Alpine’s beans will have small amounts of dairy, while the casein protein stream will have small amounts of soy, said Richani.
“We could completely purify it, but it defeats our purpose; the higher the purity the higher the costs. We can still make highly functional cheeses with a combination of casein and soy protein, and [as for selling casein proteins as a b2b supplier down the road] you’d be surprised at how many products from pizza to nutrition bars contain dairy and soy, so we don’t see it limiting our market.
“For the soy protein stream, we’re looking at areas such as pet foods, where companies we’ve talked to are not concerned about having some dairy in there. What matters is will this taste good and function the way I need it at the right price?”
Allergen management
Asked about allergen management, about which the FDA recently issued a warning to companies in the molecular farming space, she said: “Building a supply chain where you are controlling for allergens has been a big focus for us in the last few years. You can get all the science right but if you mess up your supply chain, that’s taking the whole industry backwards and we can’t afford to do that.”
Funding molecular farming
As for funding, “There’s no denying that the markets are very different today,” said Richani, who raised a $75 million series B round in summer 2021, “But I don’t think it’s necessarily bad. It brings more discipline, which in the long term, I think helps the space.
“And actually there has been more interest in the molecular farming category lately, so we’ve been getting inbound inquiries from investors as there is an acknowledgement that this technology [vs precision fermentation] has the potential to get us to price parity [with dairy produced from cows].”
She added: “Put it this way, when I started this company, I spoke to a lot of investors that said, ‘Why would anybody produce casein in plants when you can easily do it via fermentation?’ The same people are now coming back and saying , ‘Actually what you’re doing makes a lot of sense.’”
The timetable
Right now, Alpine has “USDA permits, plants in the ground, and internal pilot capabilities, so we can process and optimize our purification processes,” said Richani, who is going through the self-GRAS process for Alpine’s ingredients and then plans to submit a GRAS determination to the FDA.
“We’re doing tastings [for Nobell Foods cheese] mostly internally this year, and then next year we’re planning to do our first public tastings.”
On the processing side, she said, “Maybe 90% of the process and the infrastructure and the equipment needed is already in place, so we might need maybe to add one unit of operation at the most.”
What is molecular farming?
There are varying definitions, but companies deploying plant molecular farming are typically genetically engineering plants to make them produce something they wouldn’t typically make (think vaccines made in tobacco, growth factors made in barley, dairy proteins in potatoes, chymosin made in safflower).
Rather than modifying the plant to confer a beneficial agronomic property such as disease resistance, stress tolerance, increased yields, or improved nutrition (eg. purple tomatoes); molecular farming companies use plants like bioreactors in order to produce specific high-value ingredients.
In recent years, multiple players have emerged producing so-called ‘animal-free’ proteins through molecular farming, which they argue is more sustainable, ethical, and potentially more efficient than industrialized animal agriculture.
Techniques vary, with some players such as Iceland’s ORF Genetics developing transgenic crops where foreign DNA that codes for the target protein is inserted into the plant’s genome such that its ability to produce the target protein (in this case, growth factors, costly signaling proteins used in cell culture) is passed along to the next generation.
Other players such as US-based Forte Protein use transient or temporary expression systems whereby the gene of interest is introduced into the plant cells such that they express the target protein (Forte is working on proteins including lactoferrin and bovine serum albumin), but the plant’s genetic makeup remains unchanged.
Other players to watch in the molecular farming space include:
- Dairy proteins: Mozza, Miruku (New Zealand), IngredientWerks (USA), Veloz Bio (Spain), Pigmentum and Finally Foods (Israel)
- Growth factors: Bright Biotech (UK), ORF Genetics (Iceland), BioBetter (Israel), Tiamat Sciences (USA), Core Biogenesis (France)
- Meat proteins: Moolec Science (registered in UK), IngredientWerks (USA), Kyomei (UK)
- Egg proteins: PoLoPo (Israel), Veloz Bio (Spain)
- Misc – incl sweet proteins, Mogroside V, enzymes, albumin: GreenLab (USA), Elo Life Systems (USA), Forte Protein (USA)
- Vaccines, therapeutics: Baiya Phytopharm (Thailand), Protalix Therapeutics (Israel), Bio Applications (Korea), KBio (USA), Eleva (Germany), InVitria (USA), Agrenvec (Spain) Diamante (Italy)
*US patent 111,952,606 B2: ‘Recombinant Milk Proteins and Food Compositions Comprising the Same.’ April 9, 2024.
