Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1994-05-10
1999-03-23
Eisenschenk, Frank C.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
5303871, 5303881, 53038822, 435 697, 435328, 536 2353, 4241301, 4241331, 4241351, 4241341, C07K 1646, A61K 39395, C07H 2104
Patent
active
058861521
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a humanized antibody specific to a human IL-2 receptor. More particularly, it relates to a humanized antibody obtained by transplantation of the complementarity- determining region (hereinafter, referred to as CDR) of a mouse monoclonal antibody B-B10 specific to a human IL-2 receptor into a human antibody, and a composition comprising said antibody as an active ingredient.
BACKGROUND OF THE INVENTION
The structure and function of the antibody related to the present invention will be first explained. Namely, such structure and function are described in details in Kabat et al.: Sequences of proteins of immunological interest, 4th Ed., 1989, NIH, U.S.A. as well as Roitt et al.: Immunology, 2nd Ed., 1989, Gower Medical Publishing, U.S.A. & U.K.
The antibody (immunoglobulin) is an antigen-specific glycoprotein as produced by B lymphocytes when a subject is sensitized with an antigen which is a foreign substance to the subject. As the human immunoglobulin, there are known 5 classes, i.e., IgG, IMP, IgA, IgD and IgE. In case of IgG, it has two light chains (L chains) of polypeptide having a molecular weight of about 25,000 and two heavy chains (H chains) of polypeptide having a molecular weight of about 51,000. Between H-L chains and between H-H chains, there is usually present a disulfide bond connecting two chains. An amino acid sequence consisting of about 100 amino acids at N terminal of each of the H and L chains is antigen-specific and represents an antigen-binding site. This part is called a variable (V) region. Subsequent amino acid sequence consisting of 400 amino acids in H chain or 150 amino acids in L chain is called a constant (C) region which is identical among all immunoglobulins belonging to a Ig Class such as IgG or IgM Class, or those belonging to a subclass such as igG.sub.1 or IgG.sub.2. It is known that human IgG may have C.kappa. or C.lambda. in L chain and C.gamma.1, C.gamma.2, C.gamma.3 or C.gamma.4 in H chain. L and H chains having one of these identified partial structures are called .kappa., .lambda., .gamma.1, .gamma.2, .gamma.3 and .gamma.4 chain, respectively.
H and L chain contain "domain structures". For instance, H chain is composed of VH, CH1, CH2, CH3 domains and hinge regions connecting CH1 and CH2 domains.
The variable region comprises four framework regions in which relatively conservative amino acid sequences are retained among various antibodies and three CDRs which are relatively variable in the amino acid sequence among different antibodies. In one molecule of an antibody which comprises two H chains and two L chains, there ar present six CDRs originated from VH and VL regions, which take steric configurations closely approached one another to form an antigen binding site.
The summary of the structure and function of the antibody is as above.
The monoclonal antibody (hereinafter, referred to as "MAb") is widely used for diagnosis and therapy in the medical field and as reagents, affinity column materials, etc. in the industrial field. The mouse MAb is readily obtained by the mouse/mouse hybridoma method.
For preparation of a human MAb which is more valuable for human therapy that a mouse MAb, various improvements have been proposed but any reliable method for establishing a producible cell line with good reproducibility and high efficiency has not been established. Because of this reason, human MAb as clinically usable is quite restricted. Also, the production of a human antibody to an antigen originated from a human being is generally impossible except any special case.
In case of a mouse, MAb specific to various antigens including antigens of human origin can be easily obtained but on administration to a human being, a problem of antigenicity occurs. Some attempts have been made to produce an antibody lowered in antigenicity to a human body from mouse MAb. Specifically, attempts are directed to the production of a humanized antibody wherein only a CDR, which is said to form an antigen-binding site, in the vari
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Gomi Hideyuki
Nakatani Tomoyuki
Noguchi Hiroshi
Wijdenes John
Biotest Pharma GbmH
Diaclone
Eisenschenk Frank C.
Sumitomo Pharmaceuticals Company Limited
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