Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1997-09-10
1999-11-23
Hutzell, Paula K.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
530326, 530350, 5303911, 5303915, 530402, 536 231, A61K 3800, C07K 100, C07K 1600, C07H 2102
Patent
active
059902752
ABSTRACT:
The invention is directed to a novel peptide linker useful for connecting polypeptide constituents into a novel linked fusion polypeptide. The peptide linker of the invention provides greater stability and is less susceptible to aggregation than previously known peptide linkers. The peptide linker of the invention may be up to about 50 amino acids in length and contains at least one occurrence of a charged amino acid followed by a proline. When used for making a single chain Fv (sFv), the peptide linker is preferably from 18 to about 30 amino acids in length. A preferred embodiment of the peptide linker of the invention comprises the sequence:
REFERENCES:
patent: 4085443 (1978-04-01), Dubois et al.
patent: 4266253 (1981-05-01), Matherat
patent: 4355023 (1982-10-01), Ehrlich et al.
patent: 4414629 (1983-11-01), Waite
patent: 4434156 (1984-02-01), Trowbridge
patent: 4444878 (1984-04-01), Paulus
patent: 4470925 (1984-09-01), Auditore-Hargreaves
patent: 4479895 (1984-10-01), Auditore-Hargreaves
patent: 4642334 (1987-02-01), Moore et al.
patent: 4704692 (1987-11-01), Ladner
patent: 4816397 (1989-03-01), Boss et al.
patent: 4816567 (1989-03-01), Cabilly et al.
patent: 4853871 (1989-08-01), Pantoliano et al.
patent: 4881175 (1989-11-01), Ladner
patent: 4908773 (1990-03-01), Pantoliano et al.
patent: 4939666 (1990-07-01), Hardman
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5091513 (1992-02-01), Huston et al.
patent: 5132405 (1992-07-01), Huston et al.
patent: 5160723 (1992-11-01), Welt et al.
patent: 5258498 (1993-11-01), Huston et al.
patent: 5260203 (1993-11-01), Ladner et al.
patent: 5476786 (1995-12-01), Huston
patent: 5534254 (1996-07-01), Huston et al.
patent: 5591828 (1997-01-01), Bosslet et al.
Batra et al., "Anti-Tac (FV)-PE40, a Single Chain Antibody Pseudomonas Fusion Protein Directed at Interleukin 2 Receptor Bearing Cells," J. Biol. Chem. 265 (25) :15198-15202 (1990).
Bedzyk et al., "Immunological and Structural Characterization of a High Affinity Anti-fluorescein Single-Chain Antibody," J. Biol Chem. 265 (30):18615-18620 (1990).
Bird et al., "Single-Chain Antigen-Binding Proteins," Science 242:423-426 (1988).
Breitling et al., "A Surface Expression Vector for Antibody Screening," Gene 104:147-153 (Aug. 1991).
Chaudhary et al., "A Recombinant Immunotoxin Consisting of Two Antibody Variable Domains Fused to Pseudomonas Exotoxin," Nature 339:394-397 (1989).
Clements, J., "Construction of a Nontoxic Fusion Peptide for Immunization against E. coli Strains That Produce Heat-Labile and Heat-Stable Enterotoxins," Infection and Immunity 58(5):1159-1166 (1990).
Colcher et al., "In Vivo Tumor Targeting of a Recombinant Single-Chain Antigen-Binding Protein," J. National Cancer Institute 82(14):1191-1197 (1990).
Condra et al., "Bacterial Expression of Antibody Fragments That Block Human Rhinovirus Infection of Cultured Cells," J. Biol. Chem. 265(4):2292-2295 (1990).
Essig et al., "Crystallization of Single-Chain Fv Proteins," J. Mol. Biol. 234:897-901 (Dec. 1993).
Fuchs et al., "Targeting Recombinant Antibodies To The Surface of E. coli: Fusion To A Peptidoglycan Associated Lipoprotein," Bio/Technol. 9:1369-1372 (Dec. 1991).
Harris and Emery, "Therapeutic Antibodies--The Coming of Age," TiBTech 11:42-44 (Feb. 1993).
Hird et al., "Immunotherapy with Monoclonal Antibodies" in: Genes and Cancer, eds. Carney et al., John Wiley & Sons Ltd., pp. 183-189 (1990).
Holvoet et al., "Characterization of a Chimeric Plasminogen Activator Consisting of a Single-Chain Fv Fragment Derived from a Fibrin Fragment D-Dimer-specific Antibody and a Truncated Single-Chain Urokinase," J. Biol. Chem. 266(29):19717-19724 (1991).
Huston et al., "Medical Applications of Single-Chain Antibodies," Int. Rev. Immunol 10(2-3):195-217 (1993).
Huston et al., "Protein Engineering of Single-Chain Fv Analogs and Fusion Proteins," Meth. in Enzymology 203:46-88 (1991).
Kim et al., "Redesigning a Sweet Protein: Increased Stability and Renaturability," Protein Eng. 2(8):571-575 (1989).
Laroche et al., "Characterization of a Recombinant Single-chain Molecule Comprising the Variable Domains of a Monoclonal Antibody Specific for Human Fibrin Fragment D-Dimer," J. Biol. Chem. 266(25):16343-16349 (Sep. 1991).
Lehninger, A.L., Principles of Biochemistry, Worth Publishers, Inc., NY, NY, pp. 150-155 (1982).
Milenic et al., "Construction, Binding Properties, Metabolism, and Tumor Targeting of a Single-Chain Fv Derived from the Pancarcinoma Monoclonal Antibody CC49," Cancer Research 51:6363-6371 (Dec. 1991).
Mottez et al., "A Single-Chain Murine Class I Major Transplantation Antigen," Eur. J. Immunol. 21:467-471 (Feb. 1991).
Novotny et al., "A Soluble, Single-Chain T-cell Receptor Fragment Endowed With Antigen-Combining Properties," Proc. Natl. Acad. Sci. USA 88:8646-8650 (Oct. 1991).
Pantoliano et al., "Conformational Stability, Folding, and Ligand-Binding Affinity of Single-Chain Fv Immunoglobulin Fragments Expressed in E. coli," Biochemistry 30(42):10117-10125 (Oct. 1991).
Schlom, J., "Monoclonal Antibodies: They're More and Less Than You Think" in: Molecular Foundations of Oncology, ed. S. Broder, Publ. Williams & Wilkins, Baltimore, MD, pp. 95-134 (1991).
Scientific Report--Ludwig Institute for Cancer Research--1991 Annual Scientific Report, Published Apr. 30, 1992.
Seehaus et al., "A Vector for the Removal of Deletion Mutants from Antibody Libraries," Gene 114:235-237 (May 1992).
Soo Hoo et al., "Characterization of a Single-Chain T-cell Receptor Expressed in E. coli," Proc. Natl. Acad. Sci. USA 89:4759-4763 (May 1992).
Takkinen et al., "An Active Single-Chain Antibody Containing a Cellulase Linker Domain Is Secreted by E. coli," Protein Eng. 4(7):837-841 (Oct. 1991).
Traunecker et al., "Bispecific Single-Chain Molecules (Janusins) Target Cytotoxic Lymphocytes on HIV Infected Cells," EMBO J. 10(12):3655-3659 (Dec. 1991).
Waldmann, T., "Monoclonal Antibodies in Diagnosis and Therapy," Science 252:1657-1661 (Jun. 1991).
Welt et al., "Quantitative Analysis of Antibody Localization in Human Metastatic Colon Cancer: A Phase I Study of Monoclonal Antibody A33," J. Clinical Oncology 8(11):1894-1906 (1990).
Whitlow et al., "An Improved Linker for Single-Chain Fv with Reduced Aggregation and Enhanced Proteolytic Stability," Protein Eng. 6(8):989-995 (Nov. 1993).
Whitlow, et al., "Single Chain Fvs," in: Tumor Immunology: A Practical Approach, Publ. by Oxford University Press, pp. 279-291 (1993).
Wootton et al., "The Q-Linker: A Class of Interdomain Sequences Found in Bacterial Multidomain Regulatory Proteins," Protein Eng. 2(7):535-543 (1989).
Yokota et al., "Rapid Tumor Penetration of a Single-Chain Fv and Comparison with Other Immunoglobulin Forms," Cancer Res. 52:3402-3408 (Jun. 1992).
Boulianne, et al., "Production of functional chimaeric mouse/human antibody," Nature 312:643-646 (1984).
Brennan, et al., "Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G.sub.1 Fragments," Science 229:81-83 (Jul. 1985).
Brewin-Wilson, D., "Cross-Linked Antibodies Turn Cytotoxic Cells against Cancer," Oncol. Biototech. News 3(6):7 (Jun. 1989).
Corvalan, J.R.F. and Smith, W., "Construction and characterisation of a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids," Cancer Immunol. Immunother. 24:127-132 (1988).
Corvalan, et al., "Tumour Therapy with Vinca Alkaloids Targeted by a Hybrid-Hybrid Monoclonal Antibody Recognising both CEA and Vinca Alkaloids," Intl. J. Cancer Supp. 2:22-25 (1988).
Cumber, et al., "Comparative Stabilities in Vitro and in Vivo of a Recombinant Mouse Antibody FvCys Fragment and A bisFvCys Conjugate," J. Immunol. 149(1):120-126 (Jul. 1992).
Davies, D.R. and Metzger, H., "Structural Basis of Antibody Function," Ann. Rev. Immunol. 1:87-177 (1983).
Field, et al., "Miniantibodies produced in E. coli--Fusion protein expression using dual origin vector," Dialog File 357: Biotechnology Abstracts, Accession No. 89-05519 (1989).
Field, et al., "Miniantibodies produced in E. coli--Hen egg lysozyme variable region monoclonal antibody gene
Filpula David R.
Whitlow Marc D.
Enzon Inc.
Hutzell Paula K.
Ungar Susan
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