FT. LAUDERDALE, Fla. _ Transgenic goats, sheep, pigs and cowsare competing on both sides of the Atlantic to secrete high-valuehuman proteins in their milk. Two of the top companies in thisemerging pharmaceutical field, Genzyme Transgenics Inc. (GTI), ofFramingham, Mass., and PPL Therapeutics Ltd., of EdinburghScotland, presented on the last two days of the 28th MiamiBiotechnology Winter Symposium.

On Wednesday afternoon, GTIs' director of sales and marketing,Steve Parkinson, told about his company's policies and progress incommercializing marketable proteins from goats' milk.

He told BioWorld Today, "In terms of sales, I actually brought in$750,000 in new contract business for the company in 1994. Thatcould go as high as $5 or $6 million in contract business this year."

Contract Customers Already Signed Up

As Parkinson reported to the symposium, GTI is preparing toproduce for a large (but anonymous) Japanese pharmaceuticalcompany a monoclonal antibody against a colon cancer tumormarker. "The protein has only got as far as the mouse stage at themoment," Parkinson said. "We have gotten the antibody expressed inthe mouse cell, and we do have transgenic goats with the heavy andlight chains for that antibody, but we don't have milk from themyet."

Parkinson listed among GTI's other contract customers:

* Two projects ongoing for BehringWerke, of Germany. Oneis for human anti-thrombin III, to prevent blood clots, and treatgenetic disease.

* An antibody contracted for with NeoRx Corp., of Seattle.

* Porcine liver esterase for Burroughs Wellcome Co., toresolve racemic mixtures, in which one isomer is bioactive, the othernot. This is in mice at the moment.

* Two projects for Pharmacia AB, of Stockholm, Sweden, areceptor protein and Apolipoprotein A, for which they have a modelin rabbits.

* A plasma product for COR Therapeutics Inc., in South SanFrancisco.

Parkinson said that the anti-thrombin III is closest to market. "Weare looking forward to going to the FDA with an investigational newdrug application toward the end of this year," he predicted, butadded, "Some antibodies showing very exciting results in tumorregression are likely to come to market sooner than other products."

GTI, which bases its operation on 500 pure-bred, virus-free goatsimported from New Zealand, is offering its proteins from milk as acontract manufacturing service. "What we're trying to do,"Parkinson explained, "is sign up biotech and pharmaceuticalcompanies to give us their genes, and let us make the transgenicanimal with that DNA, instead of having them do it through cellculture." Under this collaborative supply agreement with thatcompany, he added, "we would produce transgenic animals, analyzetheir milk for presence and expression level of protein, and providemilk and/or animals to the customer."

The time lag between contract signing and delivered product, hesaid, "is where nature takes over completely. We're totallyconstrained by gestation times and maturity times.

"After microinjection of transgene into egg, and putting it back in arecipient, it goes through five months of gestation before the goat'skid is born. Then it takes this transgenic kid between seven and eightmonths to develop full sexual maturity.

"At that point, it can be mated and becomes pregnant, after which itgoes through its own gestation period of five months. When theresulting transgenic nanny goat gets its first offspring, it makes itsfirst milk. This is the milk that has the human protein in it. Thewhole process takes about 18 months."

Parkinson likens this elapsed time to building a production factory."Because after 18 months we're getting large amounts of milk, andlarge volumes of protein kilogram quantities from a single goat." Atfive grams yield per liter, he told his audience," 100 kilograms ofprotein would require 31 goats."

Big Place In Market For Transgenics

Engineering a caprine mammary gland to give milk rich in a humanprotein, he explained, involves "taking a promoter sequence from thegoat's gene that codes for a milk protein, beta-casein, which is thehighest-level natural protein secreted in milk.

"We take the whole beta-casein sequence, cut out the section thatcodes for the structural protein, retain the flanking regulatorysequences. In place of the beta-casein segment, we put in a segmentthat codes for a structural human protein."

Parkinson concludes that "this technology definitely has a marketalongside cell-culture products, and alongside products derived frombacterial and yeast cells. Certainly, no one technology is likely to bethe answer to all the proteins that have to be made. But I think thereis a very big place in that market for transgenics. For complex, high-value proteins in particular, this is certain to be seen as thetechnology that is most effective."

For transgenic Anti-Thrombin III, at 5 grams per liter of goat's milk,he quotes a pre-production cost of $2 per gram, compared with $200for cell culture.

In an abstract titled "The transgenic mammary gland as a bioreactor:expectations and realizations," Alan Colman, of PPL Therapeutics,reviewed positive and negative results obtained by his company, andbriefly, by GTI as well. Using the ovine beta-lactoglobulin gene, rather than GTI's caprine beta-casein one, PPLhas successfully expressed in sheep the human genes for alpha-1-antitrypsin, Protein C and fibrinogen.

Colman did not arrive at the symposium to present his full paper. n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.