Biopharmaceuticals are medical drugs (see pharmacology) produced using biotechnology. They are proteins (including antibodies), nucleic acids (DNA, RNA or antisense oligonucleotides) used for therapeutic or in vivo diagnostic purposes, and are produced by means other than direct extraction from a native (non-engineered) biological source. [1] Plant-Made Pharmaceuticals (PMPs), also referred to as rHI, under the trade name Humulin, was developed by Genentech, but licensed to Eli Lilly and Company, who manufactured and marketed the product starting in 1982. Expression in the milk of a mammal, such as a cow, sheep, or goat, is a common application, as milk production is plentiful and purification from milk is relatively easy. Hamsters and Rabbits have also been used in preliminary studies because of their faster breeding. When a biopharmaceutical is developed, the company will typically apply for a patent, with the European requirements are perceived as more difficult to satisfy. The total number of patents granted for biopharmaceuticals has risen significantly since the 1970s. In 1978 the total patents granted was 30. This had climbed to 15,600 in 1995, and by 2001 there were 34,527 patent applications. One approach to this technology is the creation of a transgenic mammal that can produce the biopharmaceutical in its milk (or blood or urine). Once an animal is produced, typically using the pronuclear microinjection method, it becomes efficacious to use cloning technology to create additional offspring that carry the favorable modified.