Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1992-10-01
1993-11-02
Lacey, David L.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
5303873, 424 858, 435 696, 435 697, 4351723, 4353201, 536 234, 536 2353, 935 47, C07K 1500, C12N 1509, C12P 2100
Patent
active
052584984
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to novel compositions of matter, hereinafter called targeted multifunctional proteins, useful, for example, in specific binding assays, affinity purification, biocatalysis, drug targeting, imaging, immunological treatment of various oncogenic and infectious diseases, and in other contexts. More specifically, this invention relates to biosynthetic proteins expressed from recombinant DNA as a single polypeptide chain comprising plural regions, one of which has a structure similar to an antibody binding site, and an affinity for a preselected antigenic determinant, and another of which has a separate function, and may be biologically active, designed to binds to ions, or designed to facilitate immobilization of the protein. This invention also relates to the binding proteins per se, and methods for their construction.
There are five classes of human antibodies. Each has the same basic structure (see FIG. 1), or multiple thereof, consisting of two identical polypeptides called heavy (H) chains (molecularly weight approximately 50,000 d) and two identical light (L) chains (molecular weight approximately 25,000 d). Each of the five antibody classes has a similar set of light chains and a distinct set of heavy chains. A light chain is composed of one variable and one constant domain, while a heavy chain is composed of one variable and three or more constant domains. The combined variable domains of a paired light and heavy chain are known as the Fv region, or simply "Fv". The Fv determines the specificity of the immunoglobulin, the constant regions have other functions.
Amino acid sequence data indicate that each variable domain comprises three hypervariable regions or loops, sometimes called complementarity determining regions or "CDRs" flanked by four relatively conserved framework regions or "FRs" (Kabat et. al., Sequences of Proteins of Immunological Interest [U.S. Department of Health and Human Services, third edition, 1983, fourth edition, 1987]). The hypervariable regions have been assumed to be responsible for the binding specificity of individual antibodies and to account for the diversity of binding of antibodies as a protein class.
Monoclonal antibodies have been used both as diagnostic and therapeutic agents. They are routinely produced according to established procedures by hybridomas generated by fusion of mouse lymphoid cells with an appropriate mouse myeloma cell line.
The literature contains a host of references to the concept of targeting bioactive substances such as drugs, toxins, and enzymes to specific points in the body to destroy or locate malignant cells or to induce a localized drug or enzymatic effect. It has been proposed to achieve this effect by conjugating the bioactive substance to monoclonal antibodies (see, e.g., Vogel, Immunoconjugates, Antibody Conjugates in Radioimaging and Therapy of Cancer, 1987, N.Y., Oxford University Press; and Ghose et al. (1978) J. Natl. Cancer Inst. 61:657-676, ). However, non-human antibodies induce an immune response when injected into humans. Human monoclonal antibodies may alleviate this problem, but they are difficult to produce by cell fusion techniques since, among other problems, human hybridomas are notably unstable, and removal of immunized spleen cells from humans is not feasible.
Chimeric antibodies composed of human and non-human amino acid sequences potentially have improved therapeutic value as they presumably would elicit less circulating human antibody against the non-human immunoglobulin sequences. Accordingly, hybrid antibody molecules have been proposed which consist of amino acid sequences from different mammalian sources. The chimeric antibodies designed thus far comprise variable regions from one mammalian source, and constant regions from human or another mammalian source (Morrison et al. (1984) Proc. Natl. Acad. Sci. U.S.A., 81:5851-6855; Neuberger et al. (1984) Nature 312:604-608; Sahagan et al. (1986) J. Immunol. 137:1066-1074; EPO application Nos. 84302368.0, Genentech; 8510
REFERENCES:
patent: 4355023 (1982-10-01), Ehrlich et al.
patent: 4474893 (1984-10-01), Reading
patent: 4642334 (1987-02-01), Moore et al.
patent: 4666837 (1987-05-01), Harford et al.
patent: 4704692 (1987-11-01), Ladner
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5091513 (1992-02-01), Huston et al.
Thiesen (1987) Chemical Abstracts 106(13), p. 37, Ab. No. 95759y.
Richardson (1987) Chemical Abstracts 107(5), p. 330, Ab. No. 35697n.
Williams et al., Gene 43 (1986) 319-324.
Sun et al., Jan. 1987, Proc. Natl. Acad. Sci., USA, vol. 84, pp. 214-218.
Liu, et al., (1987) Gene, 54:33-40.
Tan et al., (1985), J. Immunol., 135:3564-3567.
Takeda et al., (1985) Nature, 314:452-454.
Baer et al., (1985), Cell 43:705-713.
Boulianne et al., (1987) Mol. Biol. Med., 4: 37-49.
Brown et al., (1987) Cancer Research 47:3577-3583.
Gascoigne et al., (May 1987), 84:2936-2940.
Liu et al., (May 1987), Proc. Natl. Acad. Sci. USA, vol. 84, pp. 3439-3443.
Chothia et al., J. Mol Biol. (1987), 196:901-917.
Sharon et al., (1976), Biochemistry 15:1591-4.
Sahagan et al., (1986), J. Immunol. 137:1066-74.
Dammacco et al. (1972) J. Immunol. 109:565-569.
Huston et al. (1972) Biochem. 11:4256-4262.
Inbar et al. (1972) PNAS (USA) 69:2659-2662.
Hockman et al (1973) Biochemistry 12:1130-1138.
Sharon and Givol (1976) Biochemistry 19:4091-4096.
Rosemblatt and Haber (1978) Biochemistry 17:3877-3882.
Itakura et al (1979) Science 198:1056-1063.
Kabat et al (1979) PNAS (USA) 75:2429.
Ehrlich et al (1980) Biochemistry 19:4091-4096.
Wetzel et al (1981) Gene 16:63-71.
Rice and Baltimore (1982) PNAS (USA) 79:7862-7865.
Haber (1983) Biochem. Pharmacol. 32:1967-1977.
Boulianne et al (1984) Nature 312-543-646.
Cabilly et al (1984) PNAS (USA) 81:3273.
Morrison et al (1984) Science (WDC) 229:1202.
Neuberger et al (1984) Nature 312:604-608.
Abstract A: Blue Sheets 5:s5 (Jul. 3, 1985).
Haber and Norotny (1985) Hybridoma Technology in the Biosciences and Medicine, Plenum Publishing Corp. pp. 57-76.
Marx (1985) Science 229:455-456.
Ohno et al (1985) PNAS 82:2945-2949.
Abstract B (Jan. 27, 1986) SBIR Phase I.
Arnon (1986) Chem Abstr. vol. 105 No. 5 p. 1.
Greenberg (1986) G.E. News (Dec.).
Jones et al. (1986) Nature 321:522-525.
Klausner (1986) Biotechnol. 4:1041-1043.
Neuberger (1986) Chem. Abstr. vol. 105 No. 11 p. 475.
Newsmatch (1986) "Genex makes a miniturized monoclonal antibody" Monday, Oct. 20, 1986 p. 5.
Pollack et al (1986) Science 234:1570-1573.
Sahagan et al. (1986) J. Immunol. 109:565-569.
Sun et al (1986) Hybridoma vol. 5 Suppl. 1:17-20.
Tramontano et al (1986) Science 234:1566-1570.
Van Brunt (1986) Biotechnology 4:277-283.
Corvalan and Smith (1987) Caner Immuno. Immunother. 24:127-132.
Coravalen et al (1987) Cancer Immunol. Immunother. 24:133-137.
Richardson et al (1987) Chem Abstr. vol. 107 No. 5 p
The United States Government has rights in this application pursuant to small business innovation research grant numbers SSS-4 R43 CA39870-01 and SSS-4 2 R44 CA39870-02.
Huston James S.
Oppermann Hermann
Budens Robert D.
Creative BioMolecules, Inc.
Lacey David L.
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