Hybrid immunoglobulins

Details Hybrid immunoglobulins Hybrid immunoglobulins

1997-08-05

2002-06-18

Ulm, John (Department: 1646)

Drug, bio-affecting and body treating compositions

Conjugate or complex of monoclonal or polyclonal antibody,...

C435S069700, C514S002600, C530S350000, C536S023400

Reexamination Certificate

active

06406697

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates to novel ligand binding molecules and receptors, and to compositions and methods for improving the circulating plasma half-life of ligand binding molecules. In particular, this invention also relates to hybrid immunoglobulin molecules, to methods for making and using these immunoglobulins, and to nucleic acids encoding them.
Immunoglobulins are molecules containing polypeptide chains held together by disulfide bonds, typically having two light chains and two heavy chains. In each chain, one domain (V) has a variable amino acid sequence depending on the antibody specificity of the molecule. The other domains (C) have a rather constant sequence common among molecules of the same class. The domains are numbered in sequence from the amino-terminal end.
The immunoglobulin gene superfamily consists of molecules with immunoglobulin-like domains. Members of this family include class I and class II major histocompatibility antigens, immunoglobulins, T-cell receptor &agr;, &bgr;, &ggr; and &dgr; chains, CD1, CD2, CD4, CD8, CD28, the &ggr;, &dgr; and &egr; chains of CD3, OX-2, Thy-1, the intercellular or neural cell adhesion molecules (I-CAM or N-CAM), lymphocyte function associated antigen-3 (LFA-3), neurocytoplasmic protein (NCP-3), poly-Ig receptor, myelin-associated glycoprotein (MAG), high affinity IgE receptor, the major glycoprotein of peripheral myelin (Po), platelet derived growth factor receptor, colony stimulating factor-1 receptor, macrophage Fc receptor, Fc gamma receptors and carcinoembryonic antigen.
It is known that one can substitute variable domains (including hypervariable regions) of one immunoglobulin for another, and from one species to another. See, for example, EP 0 173 494; EP 0 125 023; Munro, Nature 312: (Dec. 13, 1984); Neuberger et al., Nature 312: (Dec. 13, 1984); Sharon et al., Nature 309: (May 24, 1984); Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984); Morrison et al. Science 229:1202-1207 (1985); and Boulianne et al., Nature 312:643-646 (Dec. 13, 1984).
Morrisson et al., Science 22:1202-1207 (1985) teaches the preparation of an immunoglobulin chimera having a variable region from one species fused to an immunoglobulin constant region from another species. This reference suggests molecules having immunoglobulin sequences fused with non-immunoglobulin sequences (for example enzyme sequences), however the references teaches only immunoglobulin variable domains attached to the non-immunoglobulin sequence. Morrison et al., EP 0 173 494 teaches a similar chimera. While the term “receptor” is used by the authors, and the background section refers to “receptors such as immunoglobulins, enzymes and membrane proteins”, the stated “receptors of interest” include “B-cell and T-cell receptors, more particularly, immunoglobulins, such as IgM, IgG, IgA, IgD and IgE, as well as the various subtypes of the individual groups” (page 3 lines 10-13). The disclosure of this reference is specific to immunoglobulin chimeras (see for example page 3, lines 21-30).
It has also been shown that it is possible to substitute immunoglobulin variable-like domains from two members of the immunoglobulin gene superfamily—CD4 and the T cell receptor—for a variable domain in an immunoglobulin; see e.g. Capon et al.,
Nature
337:525-531, 1989, Traunecker et al., Nature 339:68-70, 1989, Gascoigne et al.,
Proc. Nat. Acad. Sci.
84:2936-2940, 1987, and published European application EPO 0 325 224 A2.
A large number of proteinaceous substances are known to function by binding specifically to target molecules. These target molecules are generally, but need not be, proteins. The substances which bind to target molecules or ligands are referred to herein as ligand binding partners, and include receptors and carrier proteins, as well as hormones, cellular adhesive proteins, tissue-specific adhesion factors, lectin binding molecules, growth factors, enzymes, nutrient substances and the like.
Lymphocytes are examples of cells which are targeted to specific tissues. Lymphocytes are mediators of normal tissue inflammation as well as pathologic tissue damage such as occurs in rheumatoid arthritis and other autoimmune diseases. Vertebrates have evolved a mechanism for distributing lymphocytes with diverse antigenic specificities to spatially distinct regions of the organism (Butcher, E. C.,
Curr. Top. Micro. Immunol.
128, 85 (1986); Gallatin, W. M., et al.,
Cell
44, 673 (1986); Woodruff, J. J., et al.,
Ann. Rev. Immunol.
5, 201 (1987); Duijvestijn, A., et al.,
Immunol. Today
10, 23 (1989); Yednock, T. A., et al.,
Adv. Immunol
(in press) (1989)).
This mechanism involves the continuous recirculation of the lymphocytes between the blood and the lymphoid organs. The migration of lymphocytes between the blood, where the cells have the greatest degree of mobility, and the lymphoid organs, where the lymphocytes encounter sequestered and processed antigen, is initiated by an adhesive interaction between receptors on the surface of the lymphocytes and ligands on the endothelial cells of specialized postcapillary venules, e.g., high endothelial venules (HEV) and the HEV-like vessels induced in chronically inflamed synovium.
The lymphocyte adhesion molecules have been specifically termed homing receptors, since they allow these cells to localize in or “home” to particular secondary lymphoid organs.
Candidates for the lymphocyte homing receptor have been identified in mouse, rat and human (Gallatin, W. M., et al.,
Nature
303, 30 (1983) Rasmussen, R. A., et al.,
J. Immunol.
135, 19 (1985); Chin, Y. H., et al.,
J. Immunol.
136, 2556 (1986); Jalkanen, S., et al.,
Eur. J. Immunol.
10, 1195 (1986)). The following literature describes work which has been done in this area through the use of a monoclonal antibody, termed Mel 14, directed against a purported murine form of a lymphocyte surface protein (Gallatin, W. M., et al., supra; (Mountz, J. D., et al.,
J. Immunol.
140, 2943 (1988); (Lewinsohn, D. M., et al.,
J. Immunol.
138, 4313 (1987); Siegelman, M., et al.,
Science
231, 823 (1986); St. John, T., et al.,
Science
231, 845 (1986)).
Immunoprecipitation experiments have shown that this antibody recognizes a diffuse, ~90,000 dalton cell surface protein on lymphocytes (Gallatin, W. M., et al., supra) and a ~100,000 dalton protein on neutrophils (Lewinsohn, D. M., et al., supra).
A partial sequence—13 residues—for a purported lymphocyte homing receptor identified by radioactively labeled amino acid sequencing of a Mel-14 antibody-defined glycoprotein was disclosed by Siegelman et al. (Siegelman, M., et al.,
Science
231, 823 (1986)).
Lectins are proteins with a carbohydrate-binding domain found in a variety of animals, including humans as well as the acorn barnacle and the flesh fly. The concept of lectins functioning in cell adhesion is exemplified by the interaction of certain viruses and bacteria with eucaryotic host cells (Paulson, J. C.,
The Receptors
Vol. 2 P. M. Conn, Eds. (Academic Press, NY, 1985), pp. 131; Sharon, N.,
FEBS Lett.
217, 145 (1987)). In eucaryotic cell-cell interactions, adhesive functions have been inferred for endogenous lectins in a variety of systems (Grabel, L., et al.,
Cell
17, 477 (1979); Fenderson, B., et al.,
J. Exp. Med.
160, 1591 (1984); Kunemund, V.,
J. Cell Biol.
106, 213 (1988); Bischoff, R.,
J. Cell Biol.
102, 2273 (1986); Crocker, P. R., et al.,
J. Exp. Med.
164, 1862 (1986); including invertebrate (Glabe, C. G., et al.,
J. Cell. Biol.
94, 123 (1982); DeAngelis, P., et al.,
J. Biol. Chem.
262, 13946 (1987)) and vertebrate fertilization (Bleil, J. D., et al.,
Proc, Natl. Acad. Sci., U.S.A.
85, 6778 (1988); Lopez, L. C., et al.,
J. Cell Biol.
101, 1501 (1985)). The use of protein-sugar interactions as a means of achieving specific cell recognition appears to be well known.
The literature suggests that a lectin may be involved in the adhesive interaction between the lymphocytes and their ligands (Rosen, S. D., et al.,
Science
228, 1005 (1985); Rosen, S. D., et al.,
J. Imm

Affiliated with

Also associated with

Rating

Hybrid immunoglobulins does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Hybrid immunoglobulins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Hybrid immunoglobulins will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2972028