containing the DNA for a human antibody variant. The strategy may also employ synthesis of linear DNA fragments based on the reading of CDR sequences. The process requires computer-modelling software to determine which of the antibody's amino acids can be changed from murine-sequence to human-sequence without the changes compromising the conformation of the binding site. In the United States, this software was developed, patented, and demonstrated, by Protein Design Labs, Inc. in Mountain View, California, in the 1980s and 1990s. Alemtuzumab is an early example of an antibody whose humanization did not include a chimeric intermediate. In this case, a monoclonal dubbed "Campath-1" was developed to bind CD52 using a mouse system. The hypervariable loops of Campath-1 (that contain its CDRs and thereby impart its ability to bind CD52) were then extracted and inserted into a human antibody framework. Alemtuzumab is approved for treatment of B-cell chronic lymphocytic leukemia and is currently in clinical trials for a variety of other conditions including multiple sclerosis. Derivation from sources other than mice There are technologies that completely avoid the use of mice or other non-human mammals in the process of discovering antibodies for human therapy. Examples of such systems include various "display" methods (primarily phage display) as well as methods that exploit the elevated B-cell levels that occur during a human immune response. Display methods These employ the selective principles of specific antibody production but exploit micro-organisms (as in phage display) or even cell free extracts (as in ribosome display). These systems rely on the creation of antibody gene "libraries" which can be wholly derived from human RNA isolated from peripheral blood. The immediate products of these systems are antibody fragments, normally Fab or scFv. This means that, although antibody fragments created using display methods are of fully human sequence, they are not full antibodies. Therefore, processes in essence identical to humanization are used to incorporate and express the derived affinities within a full antibody. Adalimumab (Humira) is an example of an antibody approved for human therapy that was created through phage display. Antibodies from human patients or vaccine recipients It is possible to exploit human immune reaction in the discovery of monoclonal antibodies. Simply put, human immune response works in the same way as that in a mouse or other non-human mammal. Therefore, persons experiencing a challenge to their immune system, such as an infectious disease, cancer or a vaccination are