Forum: Pharming » Lactoferrine

[verwijderd] 15 januari 2008 20:00

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www.innovations-report.com/html/repor...

First transgenic kids with the human lactoferrin gene

17.12.2007

Human beings consume lactoferrin with breast milk since the very birth. Lactoferrin protects the baby from bacteria and viruses until the infant’s own immunological protection mechanism is formed. Since not all mothers have milk nowadays, human lactoferrin addition into the artificial feeding mixtures will assist in health care of new-born children. Their enteric infection death-rate will decrease by several times. Besides, lactoferrin possesses multiple other extremely useful properties, including the ability to suppress anticancer activity.

Unfortunately, a woman’s organism produces only 4-5 grams of lactoferrin per liter of milk, besides, donor milk can be infected by HIV or other dangerous viruses. So, it is impossible to fully rely on female donor milk. As the researchers failed to get lactoferrin with the help of transgenic microorganisms (the main manner of production of multiple protein drugs), there is an opportunity to make a transgenic animal which produces human lactoferrin with its own milk.

“The idea of getting lactoferrin from the milk of transgenic animals awoke our interest about ten years ago. We started our experiments with genetic construction, made great progress, after which we received transgenic mice. As a result of lengthy and laborious efforts with more than 5,000 transgenic mice, it was ascertained that the transgene was inherited by posterity, and the lactoferrin concentration is several times higher than that in the feminine breast milk. The “record-holder” mice produced up to 40 grams of human lactoferrin per liter of their milk. At that, human lactoferrin obtained from the mouse milk has turned out to be absolutely identical to the natural protein of feminine milk. Drugs and medical cosmetics based on human lactoferrin will be developed jointly with colleagues from other organizations,” says the initiator of the work I.L. Goldman, Director of Transgenebank, Institute of Biology of Gene, Russian Academy of Sciences.

Human lactoferrin industrial production is planned to be based on transgenic she-goats. A good she-goat produces as much milk as a bad cow – 1,000 liters per lactation. That is why successful efforts on creation of transgenic goats are being undertaken all over the world, their milk containing certain useful proteins. “Experiments on she-goats are limited by three circumstances: the goat is a seasonal animal in terms of the type of reproduction, the pregnancy period lasts for almost half a year. Besides, dairy goat-faming in Russia and Belarus is absent as a stock-raising branch,” says E.R.Sadchikova, Head of Transgenosis Laboratory, Institute of Biology of Gene, Russian Academy of Sciences.

The researchers from the Institute of Biology of Gene, Russian Academy of Sciences, have for the long time strived to obtain funding of this work from the Government of the Russian Federation, however, they failed. Instead, they have managed to establish a special BelRosTransgene program of the Federal State of Russia and Belarus. In 2003, the Biotechnological Center was set up in the scope of this program at the farm of the Scientific and Practical Center of the National Academy of Sciences for stock-raising in the town of Zhodino. Within four years of operation, the Belarus and Russian researchers jointly carried out a large number of experiments on creation of transgenic she-goats via “implantation” of the human lactoferrin gene into them. In the beginning, a lot of failures occurred. Finally, in late autumn of 2007, first transgenic kids were born at the biotechnological farm in the town of Zhodino, the lids were called Luck 1 and Luck 2.

“Unfortunately, since January 1, 2007, when the term of BelRosTransgene program funding expired, the Scientific and Practical Center for stock-raising of the National Academy of Sciences of Belarus had to undertake further financing of work to support the goat flock. It is assumed that when he-goats come into the “virile strength”, the first posterity will be received from them,” says Alexander Budevich, head of laboratory of the Center.

Now, the researchers are preparing a new BelRosTransgene-2 program of the Federal State of Russia and Belarus to ensure financial support for the work in the next ten years. The goats should be fed, kept warm, guarded, and the lactoferrin drugs should be developed and tested, their patents should be protected. Only after these obstacles have been overcome, it can be assumed that she-goats, which provide milk with the unique human protein, will be able to start earning their living, and that the next break-through of the native science will also turn out to be the break-through in high-technologies business of the 21st century.

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quote:
schreef:
As the researchers failed to get lactoferrin with the help of transgenic microorganisms (the main manner of production of multiple protein drugs), there is an opportunity to make a transgenic animal which produces human lactoferrin with its own milk.
[/quote]

en waar is Pharming mee bezig?

[quote]Lactoferrin (human) purified from bovine milk

www.cfsan.fda.gov/~rdb/opa-gn06.html

[verwijderd] 15 januari 2008 20:06

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www.scoop.co.nz/stories/SC0712/S00018...

New Site for GE Cows Ignores Biosecurity Questions
Monday, 10 December 2007, 9:18 am
Press Release: GE Free NZ

There is concern that a new application by AgResearch to move transgenic cows to a new site will be approved by ERMA, despite the lack of data on impacts on soil environments.

AgResearch has previously farmed on 100 acres deemed 'in containment', but the latest application opens up a whole new stage of transgenic cattle expansion around the country and any approval of the plan is tantamount to a 'conditional release'.

ERMA have been complicit in allowing amendments under the HSNO Act that have gradually eroded the stringent approach, like allowing experimental GE cattle carrying different types of human transgenes to graze together.

ERMA has allowed through non public approvals for AgResearch to carry on breeding cows, but there have been no studies on the adverse effects that the animals have on the soil or ecosystem, only the offal pits where high levels of antibiotic resistant genes were found in the surrounding soil.

The need to research and study such data has been deliberately ignored as a key element of understanding GE biosecurity risk management, even though these animals have been continuously farmed in field development conditions for seven years.

The original approval for development trials was to see if transgenic products could be pharmed from milk, and to establish if the gene was stably passed to the first generation of calves. This was not successful in cows engineered with a gene to express myelin basic protein (MBP). Only four out of sixty calves were born. The process to produce lactogobulin was unviable. Cows carrying an extra casein gene were more productive. However when AgResearch was given permission by ERMA to import embryo's containing human lactoferrin they broke the law by using transgenic cows to carry the embryo's. Despite this breach, nothing ever came of it but a 'warning'.

"This kind of deliberate disregard shows that ERMA has no will to follow the correct procedures that the Act prescribes and the public expect," says Claire Bleakley of GE Free (NZ) in food and environment. "ERMA now see GE approvals as part of their 'bread and butter' income stream, and are side stepping sound science to enable GE expansion. It is just unbelievable that ERMA would accept an application relating to a new facility without any proof from existing trials that horizontal gene transfer, or adverse effects on humans or the environmental have not occurred.

“We fear that yet again the New Zealand public is at the mercy of big business and bureaucrats willing to ignore scientific rigour to promote certain interests, and that their mistakes will leave the taxpayer and our children to clean up the contaminated sites".

"We are alarmed that yet again ERMA looks set to go through the pretence of listening to the public and to independent scientific calls for comprehensive testing for effects in GE field studies, but in reality taking not one bit of notice and instead finding ways to discount any concerns in order to approve the application," said Mrs. Bleakley.

"When in future an adverse effect shows up they will feign astonishment and pass the buck to MAF".

REFERENCES:

AgResearch application to amend controls under s67A, GMF 98009 part I &II (2007)

ERMA s67A amendment to allow the import of lactoferrin embryos www.ermanz.govt.nz

ERMA GMD 02028 Annual reports 2004-2006 www.ermanz.govt.nz

ERMA GMF 98009 Annual reports 2001 -2006 www.ermanz.govt.nz

Background Note
To date no transgenic drug from milk has been approved for oral ingestion. Most such milk-derived products have failed because of immune system reactions and deterioration in the conditions being treated. The most famous reaction to a genetically engineered drug was during the trial of an arthritis drug that caused severe immune reaction permanently impairing the health of the subjects.

[verwijderd] 15 januari 2008 22:36

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Zakcentje wat ik hoofdzakelijk uit die twee postings haal is dat het effe snel een Lacto fabriek opzetten onmogelijk is en DAT de processen omtrent Lacto productie effe snel goed gekeurd gaan worden en dat dit voor Pharming ook een hele kluif gaat worden.

Met name de footnote van het laatste artikel trok mijn aandacht:

Background Note
To date no transgenic drug from milk has been approved for oral ingestion. Most such milk-derived products have failed because of immune system reactions and deterioration in the conditions being treated. The most famous reaction to a genetically engineered drug was during the trial of an arthritis drug that caused severe immune reaction permanently impairing the health of the subjects.

[verwijderd] 18 januari 2008 07:48

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Agennix Receives Special Protocol Assessment Approval from FDA for the Pivotal Trial of Talactoferrin Alfa in First-Line Non-Small Cell Lung Cancer Trial

1/17/2008

HOUSTON, Jan. 17 /PRNewswire/ -- Agennix Incorporated announced today that the U.S. Food and Drug Administration (FDA) has approved the design of a single, pivotal, Phase 3 trial evaluating its lead molecule, talactoferrin alfa, in combination with chemotherapy as first-line treatment in patients with non-small cell lung cancer (NSCLC) under the Special Protocol Assessment (SPA) process. Separately, Agennix received Scientific Advice from the European Medicines Agency (EMEA) indicating that this single trial will also support a Marketing Authorization Application (MAA) in the European Union. Agennix had previously received Fast Track designation from the FDA for this indication.

"The Special Protocol Assessment agreement with the FDA is an important step for advancing the investigation of talactoferrin in NSCLC," said Dr. Roman Perez-Soler, Director, Division of Medical Oncology, Albert Einstein College of Medicine, New York City. "The Phase 2 data from the two separate randomized, double-blind, placebo-controlled NSCLC trials are very promising. I look forward to participating in the Phase 3 talactoferrin trials for both NSCLC indications -- first-line in combination with chemotherapy, and talactoferrin monotherapy in patients who have failed two or more previous therapies."

In the randomized, double-blind, placebo-controlled Phase 2 NSCLC trials, talactoferrin (or placebo) was administered either in combination with chemotherapy in chemo-naive patients, or as monotherapy in patients who had failed previous chemotherapy. Both trials met their prospectively defined primary endpoints -- improvement in response rate (first-line combination trial) and improvement in survival (monotherapy trial), with supporting trends on secondary efficacy endpoints. Both trials also showed statistically significant reductions in total adverse events and in significant (grade 3 or higher) adverse events in the talactoferrin arms.

Agennix is preparing to initiate Phase 3 trials in both NSCLC indications (talactoferrin in combination with chemotherapy in previously untreated patients and talactoferrin monotherapy in patients who have failed two or more previous therapies).

"Talactoferrin has the potential to be an important advance in the treatment of NSCLC," said Dr. Waun Ki Hong, head of the Division of Cancer Medicine at M.D. Anderson Cancer Center and member of Agennix's Scientific Advisory Board. "The activity and safety profile seen in the talactoferrin trials to date are very exciting and provide hope for improved treatment of this disease. I look forward to confirmation of the Phase 2 results in the Phase 3 trials."

www.biospace.com/news_story.aspx?News...

quote:
schreef:
Talactoferrin, a novel dendritic cell activator (DCA), is a unique recombinant form of human lactoferrin, an important immunomodulatory protein.

In 1988, Dr. Bert O'Malley, chair of molecular and cellular biology at Baylor College of Medicine, Houston, Texas, discovered a way to produce this protein in the laboratory, thus paving the way for testing its potential to help fight serious diseases that cause enormous suffering worldwide. "Baylor views this as exciting news, not only for the important research being done at this medical school but also for the historic battle being conducted to find effective treatments for the most lethal forms of cancer," said Dr. Peter Traber, President of Baylor College of Medicine. "It is our sincere hope that the Phase 3 trials will be successful and this drug can be eventually used globally."

[verwijderd] 30 januari 2008 14:41

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Omega-3 formulation issues need fast resolution: study
By Stephen Daniells

30/01/2008 - The increasing formulation and fortification of foods with different types of omega-3 polyunsaturated fatty acids (PUFAs) could be further enhanced by better understanding of how to protect them from oxidation, states a new review.

Writing in the journal Trends in Food Science & Technology, researchers from the Technical University of Denmark and the University of Massachusetts stated that, although omega-3-containing food is one of the fastest growing categories in Europe and the US, several challenges and gaps in the knowledge exist.

The key, states lead author Charlotte Jacobsen, is a better understanding of antioxidants and their ability to protect the fatty acids from oxidation.

"The aim is to provide a better base for predicting the protective effects of antioxidants and other antioxidative measures in food emulsions in general and in functional food systems enriched with omega-3 PUFA in particular," wrote Jacobsen.

According to market researcher Packaged Facts omega-3 enriched foods make up the strongest sector of the functional foods market in the US - and there is still room there for significant growth. The market for these goods has grown from approximately $100m to more than $2bn in four years. The firm predicts this category will reach $7bn in sales by 2011.

However, fish oil is notoriously difficult to incorporate into formulations since it is highly susceptible to oxidation. The result is a fishy taste and smell which can be off-putting for consumers.

On the other hand, the nutritional properties of fish oil have been much in the spotlight in recent years, especially omega-3, of which fish is recognized as the best source. In order to help people consume omega-3 in their diet - and especially those who have an aversion to fish - formulators have sought to overcome the stability issues and deliver food products that are untainted by sensory issues.

Jacobsen and co-workers note that the type of food matrix greatly influences the efficacy of select antioxidants to slow or stop oxidation of the fatty acids.

"Until now, selection of the most efficient antioxidants, and determination of other workable principles to retard oxidation in different n-3 PUFA enriched food emulsion systems have been encircled by systematic experimental work," they state.

The principal antioxidants employed to date include EDTA, tocopherols (vitamin E), ascorbic acid (vitamin C), lactoferrin (a milk glycoprotein), gallic acid, and some plant extracts, with the majority used in mayonnaise, salad dressings, and milk products.

However, this trial-and-error approach could be replaced by mathematical and kinetic descriptions, which are currently "clearly lacking".

"Notably, there is a scarcity of knowledge on the movement and redox changes of transition metal ions in heterophasic (many phase) systems such as food emulsions.

"In addition, an estimate of the rates of lipid peroxide diffusion and antioxidant reactivities in different phases of emulsions is missing.

"Provision of a better quantitative understanding of oxidation events and notably of antioxidant reactions in heterophasic food emulsions would allow a much better prediction of effects of antioxidants in foods.

"This knowledge is indispensable for fast, rational design and successful development of functional food products containing non-oxidized n-3 PUFA that are efficiently protected against oxidation," they concluded.

Previously, this website has reported on the potential of a range of antioxidants, predominantly natural, to retard the oxidation of omega-3 fatty acids. These included oregano and rosemary extracts, and chardonnay grape and raspberry extracts.

Source: Trends in Food Science & Technology
February 2008, Volume 19, Issue 2, Pages 76-93
"Antioxidant strategies for preventing oxidative flavour deterioration of foods enriched with n-3 polyunsaturated lipids: a comparative evaluation"
Authors: C. Jacobsen, M.B. Let, N. Skall Nielsen, A.S. Meyer

[verwijderd] 29 februari 2008 18:46

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Breast milk compound could fight cancer

George Joseph in New York

in.rediff.com/news/2008/feb/26breast.ht

February 26, 2008 17:18 IST

Children are born with underdeveloped immune systems; lactoferrin, a compound found in mother's milk, helps them develop it.

A slight variation of lactoferrin, known as talactoferrin alfa, helps fight lung cancer, according to research by Dr Atul Varadhachary, president and chief operating officer of the Houston-based Agennix.

The researcher is now in the final stages of fashioning a drug based on his discovery.

The Food and Drug Administration has approved the design of a single, pivotal, Phase 3 trial to see if talactoferrin alfa can indeed fight the most common form of lung cancer in combination with chemotherapy, as a first line of treatment.

The European Medicines Agency also said that this single trial would support a marketing authorisation application in the European Union for the drug.

The new drug could be in the market by 2010, said Varadhachary, a physician who went on to become a businessman and social activist.

Agennix has already spent $101million to develop the drug, and Varadhachary expects to spend another $100 million before it reaches the market.

The treatment of this form of lung cancer (called nonsmall cell lung cancer) is a $4 billion-a-year industry in the US alone, making the prospects bright for the company.

After breast cancer in women and prostate cancer in men, lung cancer is the most common type of cancer.

But it is more damaging than other forms of cancer because it kills more Americans than breast, prostate and colorectal cancers combined -- more than 160,000 people last year.

Another 300,000 are diagnosed as having the cancer annually in Europe, and 520,000 are diagnosed annually in the rest of the world.

For patients diagnosed with advanced NSCLC, the expected survival is only about 8.5 months, even after multiple doses of toxic chemotherapy.

Varadhachary says he is hopeful that talactoferrin will prove to be an important tool in the treatment of this cancer, pointing out that lung cancer is usually detected only when it is in very advanced stage.

Talactoferrin alfa comes in liquid form, and is to be taken in two 15-milliliter doses a day.

It can be used by any patient as it has almost no toxicity, he claimed.

"Half the patient population can't take some of the recently approved drugs because of their toxicity. Ours would apply to the entire population," he said.

The Phase 3 trial will be conducted at more than 200 sites around the world and will involve several thousand patients, Dr Varadhachary said.

If no new public health concerns surface in relation to the drug, then the FDA could grant marketing approval.

The discovery of talactoferrin occurred in 1988 when Baylor College of Medicine scientist Dr Bert O'Malley produced the protein in his laboratory from a fungus called Aspergillus niger.

Structurally, it is almost identical to human lactoferrin, which is found in mother's milk.

Breast-fed babies fight infections better, in part, because of lactoferrin, Dr Varadhachary said.

"It helps in our gut. We started looking at it and wondered if it would be helpful to stimulate the immune system... and thus fight cancer," he said.

Lactoferrin, the most abundant non-whey protein in milk, is an important part of breast milk's magic.

Babies are born with an underdeveloped immune system, and lactoferrin found in milk helps strengthen their immunity.

But strengthening the immune system can be important in cancer patients as well.

Talactoferrin has been tested in several cancer trials, with promising results.

Two of the larger trials -- placebo controlled trials in patients with lung cancer -- were conducted at 11 major cancer centers in India, including sites in Bangalore, Chennai, Delhi, Hyderabad, Mumbai, and Pune.

These trials suggested that talactoferrin could fight cancer.

In fact, in both trials, the patients receiving talactoferrin had fewer severe adverse events than those receiving the placebo, Dr Varadhachary said.

Agennix has a contract with Capua, Italy, to produce Talactoferrin on a commercial scale.

A Netherlands company is already producing it in a large quantity for the trial. The company is also trying to see if the drug can fight diabetes and other forms of cancer, too.

Dr Varadhachary, who studied medicine in Mumbai, joined Agennix in 2001, and helped refocus the company, among other things pushing it into the fight against cancer.

Excitement at Agennix has increased steadily over the last six years after they saw encouraging anti-cancer results, first in animal experiments, then in early patient trials and finally in larger Phase II trials, Dr Varadhachary said.

"Talactoferrin has the potential to be an important advance in the treatment of NSCLC," said Dr Waun Ki Hong, head of the Division of Cancer Medicine at M D Anderson Cancer Center and a member of Agennix's Scientific Advisory Board.

Dr Varadhachary who came to the US in 1987, earned a PhD in physiology and did a postdoctoral fellowship in biochemistry at the Johns Hopkins University School of Medicine in Baltimore.

While at Hopkins, he was also the founding president of the Johns Hopkins Postdoctoral Association. Soon he joined the global management consulting firm, McKinsey & Co.

His wife Gauri is an associate professor at MD Anderson Cancer Center in Houston.

In 1998-99, while on leave from McKinsey, he worked for a year with Pratham, in Mumbai.

Atul and Gauri started Pratham Health, a preventive health and micronutrient program that reaches over 50,000 pre-school children each year.

Their work was honoured by Children's Hope India, which presented them with a 'Making a Difference' award in 2001.

Pratham Health was later spun out as a separate organisation -- the Niramaya Health Foundation.

Dr Varadachary serves as the president of the Indo-American Chamber of Commerce of Greater Houston.

His academic affiliations include adjunct professorships at the Baylor College of Medicine and at the Jesse Jones School of Management at Rice University, where he teaches a course on entrepreneurship in biotechnology.

Agennix, a privately held company, was founded in 1993 based on technology from the Baylor College of Medicine in Houston.

Starting in 2001, the company changed its focus to its current lead indications, including the treatment of cancer.

Aandeel Pharming Group AEX:PHARM.NL, NL0010391025

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