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Patent

Recombinant immunoglobin preparations

08 Apr 1983-
TL;DR: In this paper, a mixture of altered and native immunoglobulins, including constant-variable region chimeras, are prepared in recombinant cell culture, which contain variable regions which are immunologically capable of binding predetermined antigens.
Abstract: Altered and native immunoglobulins, including constant-variable region chimeras, are prepared in recombinant cell culture. The immunoglobulins contain variable regions which are immunologically capable of binding predetermined antigens. Methods are provided for refolding directly expressed immunoglobulins into immunologically active form.
Citations
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Patent
02 Sep 1987
TL;DR: In this article, a single polypeptide chain binding molecule has been proposed which has binding specificity and affinity substantially similar to the binding specificity of the light and heavy chain aggregate variable region of an antibody.
Abstract: The invention pertains to a single polypeptide chain binding molecule which has binding specificity and affinity substantially similar to the binding specificity and affinity of the light and heavy chain aggregate variable region of an antibody, to genetic sequences coding therefor, and to recombinant DNA methods of producing such molecule and uses for such molecule.

3,290 citations

Patent
Leonard G. Presta1
14 Jan 2000
TL;DR: In this article, the present invention concerns polypeptides comprising a variant of the Fc region, which have altered effector function as a consequence of one or more amino acid modifications in the region thereof.
Abstract: The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

1,596 citations

Patent
07 Jun 1995
TL;DR: In this article, a method for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobalin and a framework region from an accepting human immunoglobin are provided.
Abstract: Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about about 3 Å as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

1,385 citations

Patent
20 Nov 1992
TL;DR: In this paper, genetic sequences coding for bivalent single-chain antigen-binding proteins are disclosed, including all those appropriate for monoclonal and polyclonal antibodies and fragments thereof, including use as a bispecific antigen binding molecule.
Abstract: Compositions of, genetic constructions coding for, and methods for producing multivalent antigen-binding proteins are described and claimed. The methods include purification of compositions containing both monomeric and multivalent forms of single polypeptide chain molecules, and production of multivalent proteins from purified monomers. Production of multivalent proteins may occur by a concentration-dependent association of monomeric proteins, or by rearrangement of regions involving dissociation followed by reassociation of different regions. Bivalent proteins, including homobivalent and heterobivalent proteins, are made in the present invention. Genetic sequences coding for bivalent single-chain antigen-binding proteins are disclosed. Uses include all those appropriate for monoclonal and polyclonal antibodies and fragments thereof, including use as a bispecific antigen-binding molecule.

1,307 citations

Patent
15 Jun 1992
TL;DR: In this article, the authors provide a detailed discussion of the use of humanized antibody polypeptides and methods for their preparation and use, along with consensus immunoglobulin sequences and structural models.
Abstract: Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

1,293 citations

References
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Journal ArticleDOI
19 Aug 1967-BMJ
TL;DR: The elderly, increasing in numbers year by year, are a group of people who do not fit into the materialistic plan of this present affluent society and from the politicians' point of view they must be seen as a group whoDo not constitute any form of pressure group.
Abstract: dedicated minority. To commence a series of disciplinary actions would aggravate the problem by making geriatrics even less attractive and driving the staff into closer defensive attitudes. What is required is an investigation into the causes of the inferior status of geriatrics so that these may be changed. Some of the special troubles include the desperate state of the buildings in which old people are nursed, the low level of medical and nurse staffing, the poor co-operation that so often exists between the hospitals and the welfare services, and the failure to separate mentally and physically ill old people and treat them in appropriate hospitals. These disorders, and others, are clearly described in the book, but the opportunity to present constructive reforms is not taken. Change will come about only if the public conscience is effectively aroused. Dr. M. D. Enoch, postgraduate clinical tutor at the University of Birmingham and consultant psychiatrist to the Shrewsbury Hospital Group, in the last chapter of the book, \" Ready for the Scrap Heap,\" summarizes the situation: \"The elderly, increasing in numbers year by year, are a group of people who do not fit into the materialistic plan of this present affluent society. From the politicians' point of view they must be seen as a group who do not constitute any form of pressure group. The greater number of them anyway would not be able to creep to the polling booths. A great number of them cannot even write an awkward letter of protest to the press or anybody else, and anyway they have their pride. It might be said that we have provided for them, but can we really expect them to choose the role of public beggars ? \" It is surely impossible for anyone who reads this book not to feel some personal responsibility for the sufferings of the defenceless which it describes. E. WOODFORD-WILLIAMS.

641 citations

Patent
18 Jun 1982
TL;DR: In this article, a trioma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a lymphocyte which produces a corresponding antibody with specific affinity to another desired antigen.
Abstract: Antibodies having binding affinity for two desired antigens, hereinafter "recombinant monoclonal antibodies"; recombinant monoclonal antibodies produced by a quadroma cell or a trioma cell; and methods for producing recombinant monoclonal antibodies by means of a quadroma cell or a trioma cell, wherein a quadroma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a hybridoma cell which produces an antibody having specific binding affinity for another desired antigen, and wherein a trioma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a lymphocyte which produces an antibody having specific binding affinity to another desired antigen.

573 citations

Patent
20 Dec 1983
TL;DR: Muteins of biologically active proteins such as IFN-β and IL-2 in which cysteine residues that are not essential to biological activity have been deleted or replaced with other amino acids to eliminate sites for intermolecular crosslinking or incorrect intramolecular disulfide bridge formation as mentioned in this paper.
Abstract: Muteins of biologically active proteins such as IFN-β and IL-2 in which cysteine residues that are not essential to biological activity have been deleted or replaced with other amino acids to eliminate sites for intermolecular crosslinking or incorrect intramolecular disulfide bridge formation. These muteins are made via bacterial expression of mutant genes that encode the muteins that have been synthesized from the genes for the parent proteins by oligonucleotide-directed mutagenesis.

330 citations

Patent
01 Jun 1984
TL;DR: In this article, a process for isolating and purifying a precipitated heterologous protein from a host cell culture is described, including treating the host cell cell culture with a buffered solution of ionic strength suitable to solubilize most of the host protein but in which refractile heterology is substantially insoluble, and disrupting the cells to form a supernatant and an insoluble fraction.
Abstract: A process for isolating and purifying a precipitated heterologous protein from a host cell culture, including treating the host cell culture with a buffered solution of ionic strength suitable to solubilize most of the host protein but in which refractile heterologous protein is substantially insoluble, and disrupting the cells to form a supernatant and an insoluble fraction; treating the insoluble fraction with a strongly denaturing solution to solubilize the refractile heterologous protein; and recovering renatured heterologous protein.

276 citations

Patent
05 Nov 1979
TL;DR: In this article, the authors describe methods of preparing synthetic structural genes coding for the expression of mammalian polypeptides in microbial cloning systems, including plasmids suited for the transformation of bacterial hosts.
Abstract: The Specification discloses: 1. Recombinant microbial cloning vehicles comprising heterologous DNA coding for the expression of mammalian hormone (e.g., somatostatin) and other polypeptides, including plasmids suited for the transformation of bacterial hosts. The latter incorporate a regulon homologous to the host in its untransformed state, in reading phase with the structural gene for the heterologous DNA; 2. Cloning vehicles coding for the microbial expression of a protein variously comprising (a) a polypeptide hapten and additional protein sufficient in size to confer immunogenicity on the product of expression, which may find use in raising antibodies to the hapten for assay use or in the manufacture of vaccines; and (b) a desired polypeptide product and additional protein from which the desired product may be cleaved; and 3. Methods of preparing synthetic structural genes coding for the expression of mammalian polypeptides in microbial cloning systems.

275 citations