Transgenic animals

Got Rabbits? Their Milk May Treat Inhibitors Someday

PEN has printed in the past articles about coming products, like long lasting and human-cell line products. We’ve also mentioned transgenic animals—which express proteins in their milk that can be used for human treatment of certain disorders. Hemophilia is one of the therapies being researched to create products from transgenic animals.

Charlton [Massachusetts] farm to raise rabbits for medicine


A French biotechnology company that turns milk from genetically engineered goats into medicine plans to expand operations at its farm in Charlton by raising rabbits that produce a blood-clotting agent for patients with hemophilia.
LFB SA and its Framingham-based subsidiary rEVO Biologics plan to build a colony of 1,000 to 1,200 rabbits making a protein called Factor VIIa at the farm, said Dr. William Gavin, a veterinarian and senior vice president of operations for rEVO.

“We’re going to have the first shovel in the ground in August,” Dr. Gavin said. “About one year later we will be producing milk here from the rabbits that produce the Factor VII in their mammary glands.”

The plan represents the first potential product expansion at rEVO, previously known as GTC Biotherapeutics, since it launched a clot-busting drug called ATryn in 2009. ATryn was the world’s first drug made in the milk of genetically altered animals.

LFB has been producing limited amounts of Factor VIIa in the milk of rabbits in France while also testing the protein in humans. The company said Monday it expects to launch the third and final phase of human studies this year.

If approved, LFB would market its Factor VIIa product as a treatment for hemophilia A and B patients who have developed inhibitors, or antibodies, to other clotting proteins known as Factor VIII or Factor IX.

The global market for blood disorders, including hemophilia, is estimated to reach nearly $64.7 billion by 2017, according to analyst Usha Nagavarapu in a market research report published last year by BCC Research of Wellesley.

NovoSeven, a Factor VIIa product sold by Novo Nordisk of Denmark, posted worldwide sales of 8.9 billion kroners in 2012, or about $1.6 billion in current dollars.

Founded in 1993 as part of Genzyme Corp., rEVO has offices and laboratories in Framingham. The company developed transgenic animals as an alternative to traditional biologics manufacturing.

Transgenic animal production generally starts in a laboratory, where scientists inject human genes into an early animal embryo. The embryo then gets implanted in the womb of a surrogate mother. If the procedure is successful, the animal born will carry code for a human protein in its genes. Then the animal can be bred normally to produce offspring with the human code.

That is how rEVO built its herd of goats on its 383-acre Charlton farm. Transgenic females in the herd produce milk carrying antithrombin III, a protein involved in blood clotting. The company processes the milk to a sterile powder form of antithrombin III for sale.

Dr. Gavin said rEVO plans to bring transgenic New Zealand White rabbits from France to build a new Charlton colony. The company chose rabbits rather than goats to produce Factor VIIa because rabbits can produce the key protein with certain sugars needed for the best therapeutic results.

Rabbits can also produce 200 milliliters of milk per day, or nearly 7 ounces, and they lactate for about three weeks.

Contact Lisa Eckelbecker at Follow her on Twitter @LisaEckelbecker.

So I just saw this in the newswires… and go here to read about my visit to this farm a few years ago, and to see pictures of the goats mentioned in the articles.
You can also learn more here:
Great Book I Just Read
Bonk: The Curious Coupling of Science and Sex [Kindle]
by Mary Roach
This best selling author examines the history of the scientific study of
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From Humble Farm Animals

I’ve been to a lot of places recently, and one of the most interesting ones was the GTC Biotherapeutics farm in Charlton, Massachusetts, on Friday, May 21, to see transgenic goats.

We wrote about transgenic animals in the February issue of PEN, when I discussed hemophilia products that are being developed now. Factor produced through transgenic animals may one day become a source of factor concentrate. And if production proceeds as hoped, transgenic animals may represent a high volume and thus low-cost way to produce factor and other proteins.

What are transgenic animals? These are animals that have been genetically modified to express human therapeutic proteins in their milk. In other words, human factor can be collected by milking these animals. The source material is raw milk. And once the proteins are collected and purified, they can be used to treat diseases and genetic or metabolic disorders in humans.

Now, the goats located on the 167 acres that bridge the towns of Charlton and Spencer, Massachusetts, are not being raised to create factor, although factor IX is being produced by transgenic pigs in Virginia, and factor VII is being made by transgenic rabbits in France. The goats we visited express the protein used in ATryn®, a recombinant form of human antithrombin. Atryn® is the first transgenically produced therapeutic protein to receive FDA approval and the first recombinant antithrombin approved in the U.S. So as wild as this all sounds, GTC already has an FDA-approved, transgenically produced therapeutic in the marketplace. And GTC is hoping to initiate a clinical trial for their factor VIIa product later this year.

I requested a tour, and was enthusiastically greeted by Ashley Lawton, Vice President, Business Development. Before I entered the building, I had to dip my shoes into a disinfectant solution, to kill any microbes. Of course, I was wearing sandals!

Safety was stressed at every part of the two-hour tour.

Ashley told us that the goats originated from New Zealand, because this is one of the few countries free of scrapie, a fatal and degenerative disease in sheep and goats. Why use goats and not cows? Goats produce more milk and their milk has a high protein content; they also have a four-month gestation period. And they are relatively easy to breed and maintain.

GTC is a pioneer in the field of transgenic technology, and because it involves making human therapeutic proteins, regulatory agencies want extensive documentation. Everything done to the animals, from having their hoofs cleaned to operations, is documented fully.
Dr. Bill Gavin, General Manager of Operations and chief veterinarian, joined our tour and told me, “Because we were a new technology… we were held to an even higher level of safety.”

We toured the labs where the genes are spliced into the embryos. We traveled to the barns where the goats are penned. Somehow I expected sterile, see-through cubes with goats hooked up to machines. Instead, we saw adorable goats comfy in stalls, much like you’d see on any farm. The “kids” were cuddled together. Young adults were able to mingle and hang together; they even had toys to play with like bouncing balls. Goats love to climb, and these had cubes to scale.

Goats are fascinating. They are curious, sociable and always hungry! They’ll nibble on anything and eat just about anything. I couldn’t go too near them but got close enough to see these are probably the best cared for goats on earth.

I’ve been invited to view the pigs in Virginia that are being researched currently to produce factor IX; after this trip I think I need to go check it out.

Actually seeing the goats and the technology made this seem more than just a pipedream. Perhaps the biggest revelation is that we would not “drink” the treatment, which I actually believed! Once the protein is purified from the milk, it will be freeze-dried and prepared as an injectible, biological product, very much like the factor concentrates available on the market today.

I know there are those in our community who might think this is unfeasible. But for me, this is a ray of hope. Transgenic animals might be particularly attractive as a way to treat hemophilia in developing countries, where there is great need for a low cost product, and plenty of it. Do you know which countries are the top five in population?

In order: China, India, US, Indonesia, Brazil. Four of the five most populated countries on earth are developing countries. So it stands to reason that a huge population of people with hemophilia are underserved and in need. This wonderful tour on a warm spring day left me hopeful that plentiful help for them might someday come from this fascinating new technology from humble farm animals.

Interesting Book I Just Read
The Seven Powers of Questions
By Dorothy Leeds

This book asks questions, actually: why do we talk so much and not listen? How can we better focus and learn? What are effective ways to ask questions? Leeds covers a lot of ground about how we communicate, mistakes we make in trying to form relationships (whether business or personal), and how to be a better listener. Asking questions makes us better listeners, helps us to focus, diffuse defensiveness in others, calms situations. She notes the things that make us poor listeners: having preconceived ideas, jumping to conclusions, being emotionally charged. Questions help break down those barriers, and make us more open to listen, and then to think. This book got off to a very weak start (I think it was opening with a not-so-good quote from the 1960s Star Trek TV show [and I consider myself a fan]) with a plethora of cliché quotations from oft-referenced works (Ask a better question to get a better answer: how many times have I heard that?) and also had a weak ending, by evolving into a “Where is your entire life going and how will you get motivated to be an empowered person and make your dreams come true…” But overall there is material that is vital to know and this book will be welcome to read if you are new to self-help books or any book on communication. Two stars.

Hatching a New Factor Therapy

Here’s a new post I read in the news wires: biotech start-up company Genavia Therapeutics wants to produce a blood clotting protein from chicken eggs.

Just when you think you’ve heard everything.

You may have read in my newsletter PEN about pigs that may be able to express factor through their milk glands. These are called transgenic animals. Another company here in Massachusetts wants to do this with goats.

Well, Genavia will do it with chicken eggs. It plans to use technology developed by Californian company Origen Therapeutics to produce human factor VIII. The technology involves injecting a human gene into chickens and extracting the protein from the whites of their eggs. Omelets, anyone?

Genavia chief operating officer Peter Bradley has said that this “avian transgenic technology” could cut the cost of treatment to as little as 20% of the current price. “We plan to not only take market share from the current players but to actually grow the market,” Bradley said as reported in the Waikato Times.* Now that would be something to crow about.

Stay tuned as we watch developments in this research and production; we hope to provide more information as it becomes available.

*”Start-up gets boost” by ANDREW JANES – Waikato Times, 10/03/2009

Great Book I Just Read
Beautiful Boy by David Sheff.
Heartbreaking, gutsy, honest, scary and hopeful, Sheff recounts the harrowing and bleak downward spiral of his “beautiful boy,” his teen son Nic, into a nightmarish world of drugs and addiction. This was a child who seemed to have it all: intelligence, charm, opportunities, and two caring parents. Sheff’s account is a damning testament to the devastating threat of meth to our youth, the lure drugs have to teen boys, the helplessness and anguish of families, and the sliver of hope that some teens can survive addiction. ALL parents of teens and preteens MUST read this book. Teens should read it too; it should be required reading in all grades. All of us can see ourselves on its pages: the denial (“My son wouldn’t…”), the suspicion (“Could he possibly…”) and the blame (“Where did we go wrong?”). Sheff’s skilled storytelling allows all parents to journey with him through hell and back. It’s the best book you will read all year, and the most important. Four stars.

Factor From Goats?

A persistent question we are always asked is “What ever happened to gene therapy?” We used to write extensively about this subject when gene therapy was hot, but since the deaths of two young people in gene therapy trials unrelated to hemophilia, all gene therapy seems to have taken a slow and extremely cautious route. There instead seems to be great interest in creating new and less expensive ways to manufacture factor. We recently heard of a new biotech company in California, founded by a parent of a child with hemophilia, that is developing all therapies, which hints that these products one day will be lower in cost.

And the newswires announced this last week: GTC Biotherapeutics, a Massachusetts-based biotech company, held a webcast this morning from Monaco; the webcast will be available tomorrow through the company’s website. This company “develops, produces, and commercializes therapeutic proteins through transgenic animal technology.” This means literally milking animals for the desired protein that is developed through gene therapy and then expressed through the animal’s milk.

Like many, I feel a bit skeptical but according to GTC, in August 2006 its recombinant form of human antithrombin was approved by the European Commission for use in patients with hereditary antithrombin deficiency undergoing surgical procedures. This was the first approval anywhere in the world of a therapeutic protein produced from a transgenic animal. GTC has developed goats that have the human antithrombin gene linked to a milk-protein promoting gene so that they express this protein in their milk.

In 2006, GTC was granted a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. And GTC has established a strategic collaboration with LFB Biotechnologies of France to jointly develop recombinant human factor VIIa as a potential treatment for hemophilia inhibitor hemophilia patients. This would be a direct competitor to NovoSeven, apparently. Although the article doesn’t directly state this, it implies that this recombinant FVIIa would be expressed by animals?

It bears watching, and we hope to bring more information about this through PEN and through HemaBlog. Watch the webcast yourself tomorrow at the GTC web site,

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