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Process for selection of proteinaceous substances which mimic growth-inducing molecules

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Publication number
WO1989006694A1
WO1989006694A1 PCT/US1989/000138 US8900138W WO1989006694A1 WO 1989006694 A1 WO1989006694 A1 WO 1989006694A1 US 8900138 W US8900138 W US 8900138W WO 1989006694 A1 WO1989006694 A1 WO 1989006694A1
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WO
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Patent type
Prior art keywords
growth
cells
proteinaceous
inducing
molecule
Prior art date
Application number
PCT/US1989/000138
Other languages
French (fr)
Inventor
Stuart A. Kauffman
Original Assignee
Trustees Of The University Of Pennsylvania
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/64General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host

Abstract

A method of selecting proteinaceous substances produced by recombinant DNA technique which mimic an arbitrary growth-inducing molecule is disclosed. Also disclosed is a method of selecting cells which produce proteinaceous substances which mimic an arbitrary growth-inducing molecule. A process for selecting synthetic genes which codes for a proteinaceous substance which mimics a growth-inducing molecule is also provided. The proteinaceous substances produced by this method are believed to be useful as novel drugs, vaccines, diagnostic agents or similar purposes.

Description

Process For Selection Of Proteinaceous Substances Which Mimic Growth-Inducing Molecules

Field of the Invention

This invention is directed to methods of producing novel biologically active proteinaceous substances which can be used as drugs, vaccines, diagnostic agents or similar treatments. The invention is more particularly directed to methods of selecting novel biologically active proteinaceous substances produced by recombinant DNA technique which mimic growth-inducing molecules of interest. Background of the invention Contemporary recombinant DNA techni-ques give scientists the capacity to generate large numbers of novel DNA sequences, RNA sequences, peptides, polypeptides and proteins. Some of these novel molecules, by mimicing their natural counterparts, have practical, biologically active properties and can be used as the basis for novel drugs, novel vaccines, possible tailored treatments for autoimmune diseases and new diagnostic reagents as well as other uses. Although large numbers of novel DNA sequences, RNA sequences, peptides, polypeptides and proteins such as those generated by Ballivet and Kauffman, U.S. application 942,630 filed 6/17/85, which is specifically incorporated herein by reference, can be produced, not all novel molecules produced by recombinant DNA technique are biologically active. Consequently, there exists a need for processes for quickly and easily screening those cells which produce biologically active molecules.

SUBSTITUTE SHEEΓΓ Some types of tumors have been found to proliferate by means of an autocrine mechanism or growth stimulating feedback loop. With this mechanism, a cell which has a receptor for a growth-inducing molecule will b stimulated to grow and divide by producing and secreting that same growth-inducing molecule which then binds to the receptor on or in the same cell. For example, some neoplastic transformation of cells by oncogenes and carcinogens is believed to result in the production of growth factors. Some Of these growth factors are able to bind to the receptors on the cell that secretes them, and to induce behavior indicative of a transformed phenotype which grows and divides uncontrollably. These findings have demonstrated an autocrine mechanism of transformation whereby production and secretion of growth factors by the cell which then bind to its own receptors by that factor leads to uncontrolled stimulation of the cell's own growth

Stern et al. (Science 235: 321-324, 1987) constructed in a vector a novel oncogene which expressed human epidermal growth factor (EGF) . This expression vector was transformed into a population of cells which ha EGF receptors on their surfaces. The translation product of this novel oncogene was secreted from each transformed cell and induced focus formation by binding to the cell's own EGF receptor. Thus focus formation is the consequence of autocrine loop closure and chronic autocrine stimulation.

In view of the foregoing, it is desired to provide rapid, easy methods for selecting proteinaceous substances which mimic growth-inducing molecules, methods for selecting cells which produce proteinaceous substances which mimic growth-inducing molecules and methods for selecting synthetic genes which code for proteinaceous substances which mimic growth-inducing molecules. Summary of the Invention

This invention is directed to methods for selecting proteinaceous substances which mimic growth- inducing molecules. The proteinaceous substances can be peptides, polypeptides or proteins. The choice of growth- inducing molecule is arbitrary, since the method of the invention is not restricted to any particular type of growth-inducing molecule. Specific examples include epidermal growth factor (EGF), dexamethasone and antigens. Cells which require a growth-inducing molecule to stimulate cell growth and division and which have been transformed by recombinant DNA technique to secrete proteinaceous substances not normally secreted by the cells are supplied with a growth medium deficient in the growth-inducing molecule and the cells are then grown in the medium. The subset of cells which grow and divide are then collected and the proteinaceous substance produced by the subset of cells is then isolated. In preferred embodiments of the invention the proteinaceous substances are the translation products of the synthetic genes in the expression vector. Novel peptides, polypeptides or proteins which mimic the growth-inducing molecule will bind to the receptor for the molecule, thus closing the autocrine loop and stimulating cell growth and division. This process allows the rapid and easy detection of cells which secrete a peptide, polypeptide or protein with the desired growth- inducing property. Rapid, easy detection is essential when dealing with large numbers of molecules which potentially have growth-inducing activity. The invention is also directed to methods of selecting cells which produce a proteinaceous substance which mimics a growth-inducing molecule. Cells which require a growth-inducing molecule to stimulate cell growth and division and which cells have been transformed by recombinant DNA technique to produce proteinaceous substances not normally produced by the cells are supplied with a growth medium deficient in the growth-inducing molecule. The cells are then grown in the medium and the subset of cells which grow and divide are then isolated. In preferred embodiments of the invention the proteinaceous substances are the translation products of the synthetic genes in the expression vector. The invention further relates to processes for selecting synthetic genes which code for a proteinaceous substance which mimics a growth-inducing molecule. Expression vectors which contain synthetic genes which cod for a proteinaceous substance are used to transform cells which require a growthrinducing molecule to stimulate cell growth and division thereby causing the cells to produce a proteinaceous substance which is the translation product o the synthetic genes in the expression vector. The transformed cells are grown in a growth medium deficient i the growth-inducing molecule. The subset of cells which grow and divide are then isolated. The subset of cells containing an expression vector comprising synthetic genes which mimic the growth-inducing molecule of interest are generally the only cells which grow and divide and can be easily harvested.

Detailed Description of the Invention

The term synthetic genes refers to DNA sequences which are the result of manipulation by laboratory techniques. The term natural gene refers to DNA sequences as they are found in situ in a chromosome. Synthetic gene include stochastic (random) or partially stochastic DNA sequences as well as DNA sequences which are composed of parts of a natural DNA sequence and stochastic DNA sequences or particular nucleotides. The term synthetic gene also includes DNA sequences composed of a plurality o DNA sequences derived from natural genes.

The term recombinant DNA technique refers to the techniques of producing synthetic genes, inserting the DNA sequences into expression vectors, and transforming cells with expression vectors. Illustrations of the recombinant DNA technique used in the invention are set forth in detai below in the section entitled Recombinant DNA Technique which has two subsections, A.Production of Synthetic Genes and B. Transformation of Cells.

Recombinant DNA Technique Although a large number of methodologies may be employed in the practice of the invention, the following are illustrative of certain, preferred embodiments. A. Production of Synthetic Genes

Commercially available, prepared restriction enzyme linkers which can be ligated in random order and generate codons for all twenty amino acids without generating stop codons in any reading frame or in either orientation (e.g. octameric linkers purchased from New England Biolabs) are used in the invention. Examples of linkers suitable for use in the invention include Clal, Ndel, Hindlll, Sail, Pstl and EcoRI. Equimolar or other mixtures of the linkers are ligated together using T4-DNA ligase (Boehringer and Mannheim Biochemicals) using the procedure of Maniatis et al. , Molecular Cloning, A Laboratory Manual, (Cold Spring Harbor Laboratory, 1982), which is specifically incorporated herein by reference. After ligation is complete, the ligated linkers are partially digested with one or several of the restriction enzymes for any of the linkers used to make the sequences such as EcoRI enzyme (Boehringer and Mannheim Biochemicals) according to the manufacturer's instructions. The digested mixture is then separated on a gel such as a 0.7% agarose gel using a standard borate buffer system according to the method of Maniatis (see reference above) . The fragments of desired size range(s) of DNA sequences are cut from the gel and isolated according to the method of Maniatis et al. , (see above reference) . The isolated fragments are then cloned into a restriction enzyme cleavage site or sites of an expression vector that causes secretion from the cell of the peptide or protein which is the translation product of the synthetic genes which have been cloned into the expression vector.

For example, the expression vector pUCDS3 constructed according to the method in Stern et al. , Science 235: 231-235, (1987) which is specifically incorporated herein by reference, can be used in the invention. This expression vector is constructed by modifying pFBl which consists of a partial Sau 3A fragment containing the Moloney murine leukemia virus long terminal repeat (LTR) cloned into the Bam HI site of pUC13. This expression vector was constructed by J. Morgenstern and H. Land of the Whitehead Institute. The single Eco Rl site of pUCl was destroyed by cleaving with EcoRI, filling in, and religating to produce pFBl RI. The Nde I-Pst I fragment of immunoglobulin heavy chain complementary DNA clone 17.2.25 of Loh et al.. Cell 3_3_: 85, (1983), which is specifically incorporated herein by reference, which contains sequences endcoding the signal peptide, was modified by oligonucleotide-directed mutagenesis according to the method of Dalbadie-McFarland, et al. f Proc. Natl. Acad. Sci. U.S.A. 79.: 6409, (1982) which is specifically incorporated herein by reference, to create an Eco Rl site. The fragment excised by cleavage at the Ava II site upstream from the coding sequences and at the newly created Eco Rl site was joined to pFB RI cleaved with Sal I and Hind III by using Ava II-pseudo-Sal I and Eco Rl-Hind III adapters to yield pUCDS2. A chemically synthesized gene encoding human EGF, prepared according to the method of Hare et al.. J. Cell Biochem. Suppl. 8A: 87, (1984), which is specifically incorporated herein, was provided with an Eco Rl site and upstream sequences encoding the first three a ino acids of immunoglobulin 17.2.25 and subcloned into pUC8. The Hpa I-Bam HI fragment containing the SV40 polyadenylation site was provided with synthetic Hpa I-Sal I and Bam HI-Hind III adapters and cloned into pUC8 adjacent to the EGF gene. The Eco Rl-Hine III fragment containing the EGF gene and polyadenylation site was then cloned into pUCDS2 to produce pUCDS3. The expression vector is modified by removing the fragment containing the epidermal growth factor (EGF) gene using restriction enzymes Sail and EcoRI. The expression vector is then purified by methods known in the art. The ligated linkers are partially digested using Sail and EcoRI restriction enzymes and the fragments are purified and isolated as described above. The fragments are then ligated into the purified expression vector using T4-DNA ligase. Other expression vectors which cause the cell to secrete from the cell the peptide or protein coded by the synthetic gene are also useful in the invention. A signal peptide can be cloned into expression vectors without a signal peptide in a position adjacent to the synthetic genes coding for the peptides or proteins to cause the cell to secrete the peptides or proteins using methods known in the art. Signal peptides such as a mouse immunoglobulin heavy-chain signal peptide or the random sequences of Kaiser et al.. Science 235: 312-317, (1987) may be used in the invention.

The ligated linkers should be partially digested with the same restriction enzymes used in the expression vector to create the site for the synthetic genes so that the ends of the ligated linkers will fit the restriction enzyme sites. However, if the ligated linkers have not been partially digested in this way, the ends of the fragments can be modified using other cloning procedures known in the art for these and other synthetic genes such as blunt end ligation. The library of synthetic genes cloned into the expression vectors is then inserted into cells which lack a growth-inducing molecule. B. Transformation of Cells

Cells can be transfected by methods such as the calcium phosphate coprecipitation method of Wigler et al.. Cell jLl: 223-232 (1977) ; the polyethylene glycol 6000 calcium phosphate treatment method of Sutherland and Bennett, Cancer Research 44(7) : 2769-2772, (1984), or Sutherland et al.. Proc. Natl. Acad. Sci. USA 82(2) : 2399- 2403, (1985); or the electroporation method of Toneguzzo et al.. Mol. Cell Biol. 6(2) : 703-706, (1986) or Potter et al., Proc. Natl. Acad. Sci 8 7161-7165, (1984), all of which are specifically incorporated herein by reference. Cell Culture

Cells which need a growth-inducing molecule to stimulate cell growth and division are suitable for use in the invention. Human diploid fibroblast cells such as WI- 38, a cell line which requires the addition of exogenous growth factors to stimulate cell growth and division or B lymphocytes are exemplary for use in this invention. These cells are transformed with expression vector which includes synthetic genes as provided above. In the case of WI-38, the cells are then grown according to the method of

Phillips and Cristofalo, Experimental Cell Research 134: 297-302, (1981), except that the medium does not include the growth-inducing molecule which is being sought.

Cells which grow and divide in this medium are then presumed to be synthesizing a proteinaceous substance which mimics the growth-inducing molecule not included in the medium. This proteinaceous substance is the translation product of the synthetic genes which were inserted into the cell via the expression vector. These cells are isolated and the proteinaceous substance characterized using methods for identifying peptides, polypeptides and proteins known in the art. Methods used to identify the proteinaceous substance will vary accordin to the type of proteinaceous substance. It is within the scope of the invention to select proteinaceous substances which mimic arbitrary antigens, i.e. the selection method can be used to search for proteinaceous mimics of any antigen of interest. In this case, synthetic genes inserted into an expression vector, such as the system described above, are inserted into B lymphocytes, or other immune system cells, with antibody receptor molecules on their surface against the same external antigenic determinant. If a proteinaceous substance produced by a B lymphocyte which is the translation product of the synthetic genes mimics the antigen, this proteinaceous substance will bind to antibodies on that B lymphocyte which are functioning as receptors. This binding of the proteinaceous substance which mimics the antigen should stimulate the lymphocyte to divide.

The proteinaceous substances which mimic the growth-inducing molecule of interest are believed to be useful as drugs, vaccines, diagnostics or similar purposes. It is also within the scope of the invention to select novel genes which produce the proteinaceous substances which mimic the growth-inducing molecule of interest. After a proteinaceous substance has been found which mimics the growth-inducing molecule of interest, the expression vector which carries the genes for the proteinaceous substance is removed from the cells which produce the proteinaceous substance. Then the expression vector is analyzed by methods known in the art to determine the sequence of DNA bases which codes for the proteinaceous substance. Once the base sequence of the gene coding for the proteinaceous substance is known, the base sequence and, correspondingly, the proteinaceous substance can be altered by methods known in the art in order to improve the ability of the proteinaceous substance to mimic the growth-inducing molecule of interest or otherwise to improve the practice of the embodiments of this invention. In the first case, the altered gene is inserted into an expression vector which is then inserted into a cell which lacks a growth-inducing molecule necessary for cell growth and division. The selection procedure which has been previously described for selecting a proteinaceous substance which mimics a growth-inducing molecule is then followed.

Claims

I claim
1. A process for selecting a proteinaceous substance which mimics a growth-inducing molecule comprising the steps of: a. providing cells which require a growth- inducing molecule to stimulate cell growth and division and which have been transformed by recombinant DNA technique to secrete proteinaceous substances not normally secreted by said cells; b. supplying said cells with growth medium deficient in said growth inducing molecule; c. growing said cells in said medium; d. collecting a subset of said cells which grow and divide; and e. isolating said proteinaceous substance from said subset of said cells.
2. The process of claim 1 wherein said proteinaceous substance is the translation product of synthetic genes.
3. The process of claim 1 wherein said proteinaceous substance is a peptide.
4. The process of claim 1 wherein said proteinaceous substance is a protein.
5. The process of claim 1 wherein said growth- inducing molecule is epidermal growth factor.
6. The process of claim 1 wherein said growth- inducing molecule is dexamethasone.
7. The process of claim 1 wherein said growth- inducing molecule is an antigen.
8. The process of claim 1 wherein said cells are a human diploid fibroblast.
9. The process of claim 8 wherein said human diploid fibroblast is WI-38.
10. The process of claim 1 wherein said cells are immune system dells.
11. The process of claim 10 wherein said immune system cells are B lymphocytes.
12. A process of selecting cells which produce a proteinaceous substance which mimics a growth-inducing molecule, said proteinaceous substance being the translation product of synthetic genes introduced into said cells by a recombinant DNA technique, comprising the steps of: a. providing cells which require a growth- inducing molecule to stimulate cell growth and division and which cells have been transformed by recombinant DNA technique to produce proteinaceous substances not normally secreted by said cells; b. supplying said cells with a growth medium deficient in said growth-inducing molecule; c. growing said cells in said medium; and d. isolating a subset of said cells which grow and divide.
13. The process of claim 12 wherein said proteinaceous substance is the translation product of synthetic genes.
14. The method of claim 12 wherein said proteinaceous substance is a peptide.
15. The method of claim 12 wherein said proteinaceous substance is a protein.
16. The process of claim 12 wherein said growth- inducing molecule is epidermal growth factor.
17. The process of claim 12 wherein said growth- inducing molecule is dexamethasone.
18. The process of claim 12 wherein said growth- inducing molecule is an antigen.
19. The process of claim 12 wherein said cells are a human diploid fibroblast.
20. The process of claim 19 wherein said human diploid fibroblast is WI-38.
21. The process of claim 12 wherein said cells are immune system cells.
22. The process of claim 21 wherein said immune system cells are B lymphocytes.
23. A process for selecting synthetic genes which code for a proteinaceous substance which mimics a growth- inducing molecule comprising the following steps: (a) . providing expression vectors which contain synthetic genes which code for a proteinaceous substance; (b) . transforming cells which require a growth- inducing molecule to stimulate cell growth and division to include said expression vector thereby causing said cells to produce a proteinaceous substance which is the translation product of said synthetic genes in said expression vector; (c) . supplying said transformed cells with growth medium deficient in said growth-inducing molecule;
(d) . growing said transformed cells in said growth medium;
(d) . isolating a subset of said cells which grow and divide;
(e) . removing said expression vector from said subset of said cells which grow and divide; and
(f) . analyzing said synthetic genes in said expression vector.
24. The process of claim 23 wherein said proteinaceous substance is a peptide.
25. The process of claim 23 wherein said proteinaceous substance is a protein.
26. The process of claim 23 wherein said growth- inducing molecule is epidermal growth factor.
27. The process of claim 23 wherein said growth- inducing molecule is dexamethasone.
28. The process of claim 23 wherein said growth- inducing molecule is an antigen.
29. The process of claim 23 wherein said cells are a human diploid fibroblast.
30. The process of claim 29 wherein said human diploid fibroblast is WI-38.
31. The process of claim 23 wherein said cells are immune system cells.
32. The process of claim 31 wherein said immune system cells are B lymphocytes.
PCT/US1989/000138 1988-01-15 1989-01-13 Process for selection of proteinaceous substances which mimic growth-inducing molecules WO1989006694A1 (en)

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Cited By (129)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270163A (en) * 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands
US5397706A (en) * 1991-11-06 1995-03-14 Correa; Paulo N. Serum-free basal and culture medium for hematopoietic and leukemia cells
US5427908A (en) * 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
US5432018A (en) * 1990-06-20 1995-07-11 Affymax Technologies N.V. Peptide library and screening systems
US5498530A (en) * 1991-10-16 1996-03-12 Affymax Technologies, N.V. Peptide library and screening method
US5503978A (en) * 1990-06-11 1996-04-02 University Research Corporation Method for identification of high affinity DNA ligands of HIV-1 reverse transcriptase
US5527894A (en) * 1990-06-11 1996-06-18 Nexstar Pharmacueticals, Inc. Ligands of HIV-1 tat protein
US5543293A (en) * 1990-06-11 1996-08-06 Nexstar Pharmaceuticals, Inc. DNA ligands of thrombin
US5567588A (en) * 1990-06-11 1996-10-22 University Research Corporation Systematic evolution of ligands by exponential enrichment: Solution SELEX
US5580737A (en) * 1990-06-11 1996-12-03 Nexstar Pharmaceuticals, Inc. High-affinity nucleic acid ligands that discriminate between theophylline and caffeine
US5587468A (en) * 1990-06-11 1996-12-24 University Research Corporation High affinity nucleic acid ligands to HIV integrase
US5595877A (en) * 1990-06-11 1997-01-21 Nexstar Pharmaceuticals, Inc. Methods of producing nucleic acid ligands
US5629155A (en) * 1990-06-11 1997-05-13 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to immunoglobulin E (IgE)
US5635615A (en) * 1990-06-11 1997-06-03 Nexstar Pharmaceuticals, Inc. High affinity HIV nucleocapsid nucleic acid ligands
US5637682A (en) * 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to the tachykinin substance P
US5637459A (en) * 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chimeric selex
US5639868A (en) * 1990-06-11 1997-06-17 Nexstar Pharmaceuticals, Inc. High-affinity RNA ligands for basic fibroblast growth factor
US5641629A (en) * 1990-06-11 1997-06-24 Nexstar Pharmacueticals Inc Spectroscopically detectable nucleic acid ligands
US5648214A (en) * 1990-06-11 1997-07-15 University Research Corporation High-affinity oligonucleotide ligands to the tachykinin substance P
US5654151A (en) * 1990-06-11 1997-08-05 Nexstar Pharmaceuticals, Inc. High affinity HIV Nucleocapsid nucleic acid ligands
US5660985A (en) * 1990-06-11 1997-08-26 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands containing modified nucleotides
US5668264A (en) * 1990-06-11 1997-09-16 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US5670637A (en) * 1990-06-11 1997-09-23 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands
US5674685A (en) * 1990-06-11 1997-10-07 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US5683867A (en) * 1990-06-11 1997-11-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: blended SELEX
US5686592A (en) * 1990-06-11 1997-11-11 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to immunoglobulin E (IgE)
US5688935A (en) * 1990-06-11 1997-11-18 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US5693502A (en) * 1990-06-11 1997-12-02 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5705337A (en) * 1990-06-11 1998-01-06 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-SELEX
US5707796A (en) * 1990-06-11 1998-01-13 Nexstar Pharmaceuticals, Inc. Method for selecting nucleic acids on the basis of structure
US5712375A (en) * 1990-06-11 1998-01-27 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5719273A (en) * 1993-06-14 1998-02-17 Nexstar Pharmaceuticals, Inc. Palladium catalyzed nucleoside modifications methods using nucleophiles and carbon monoxide
US5723594A (en) * 1995-06-07 1998-03-03 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US5723289A (en) * 1990-06-11 1998-03-03 Nexstar Pharmaceuticals, Inc. Parallel selex
US5726017A (en) * 1990-06-11 1998-03-10 Nexstar Pharmaceuticals, Inc. High affinity HIV-1 gag nucleic acid ligands
US5731424A (en) * 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US5731144A (en) * 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands
US5734034A (en) * 1990-06-11 1998-03-31 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors of human neutrophil elastase
US5733731A (en) * 1991-10-16 1998-03-31 Affymax Technologies N.V. Peptide library and screening method
US5750342A (en) * 1990-06-11 1998-05-12 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US5756287A (en) * 1990-06-11 1998-05-26 Nexstar Pharmaceuticals, Inc. High affinity HIV integrase inhibitors
US5763173A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5763566A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue SELEX
US5763177A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex
US5766853A (en) * 1990-06-11 1998-06-16 Nexstar Pharmaceuticals, Inc. Method for identification of high affinity nucleic acid ligands to selectins
WO1998027230A1 (en) * 1996-12-18 1998-06-25 Maxygen, Inc. Methods and compositions for polypeptide engineering
US5780228A (en) * 1990-06-11 1998-07-14 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands to lectins
US5789163A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Enzyme linked oligonucleotide assays (ELONAS)
US5789157A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5795721A (en) * 1990-06-11 1998-08-18 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of ICP4
US5797870A (en) * 1995-06-07 1998-08-25 Indiana University Foundation Pericardial delivery of therapeutic and diagnostic agents
US5811533A (en) * 1990-06-11 1998-09-22 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US5837456A (en) * 1990-06-11 1998-11-17 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to chorionic gonadotropin hormone and related glycoprotein hormones
US5837834A (en) * 1990-06-11 1998-11-17 Nexstar Pharmaceuticals, Inc. High affinity HKGF nucleic acid ligands and inhibitors
US5843701A (en) * 1990-08-02 1998-12-01 Nexstar Pharmaceticals, Inc. Systematic polypeptide evolution by reverse translation
US5846713A (en) * 1990-06-11 1998-12-08 Nexstar Pharmaceuticals, Inc. High affinity HKGF nucleic acid ligands and inhibitors
US5849890A (en) * 1990-06-11 1998-12-15 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to chorionic gonadotropin hormone and related glycoprotein hormones
US5853984A (en) * 1990-06-11 1998-12-29 Nexstar Pharmaceuticals, Inc. Use of nucleic acid ligands in flow cytometry
US5859228A (en) * 1995-05-04 1999-01-12 Nexstar Pharmaceuticals, Inc. Vascular endothelial growth factor (VEGF) nucleic acid ligand complexes
US5861254A (en) * 1997-01-31 1999-01-19 Nexstar Pharmaceuticals, Inc. Flow cell SELEX
US5864026A (en) * 1990-06-11 1999-01-26 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5869641A (en) * 1990-06-11 1999-02-09 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of CD4
US5871924A (en) * 1997-01-27 1999-02-16 Nexstar Pharmaceuticals, Inc. Method for the production of ligands capable of facilitating aminoacyl-RNA synthesis
US5874557A (en) * 1990-06-11 1999-02-23 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5874218A (en) * 1990-06-11 1999-02-23 Nexstar Pharmaceuticals, Inc. Method for detecting a target compound in a substance using a nucleic acid ligand
US5962219A (en) * 1990-06-11 1999-10-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-selex
US5972599A (en) * 1990-06-11 1999-10-26 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of cytokines
US5989823A (en) * 1998-09-18 1999-11-23 Nexstar Pharmaceuticals, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US5998142A (en) * 1993-09-08 1999-12-07 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-SELEX
US6001988A (en) * 1990-06-11 1999-12-14 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands to lectins
US6001577A (en) * 1998-06-08 1999-12-14 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex
US6011020A (en) * 1990-06-11 2000-01-04 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand complexes
US6013443A (en) * 1995-05-03 2000-01-11 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue SELEX
US6020130A (en) * 1995-06-07 2000-02-01 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands that bind to and inhibit DNA polymerases
US6028186A (en) * 1991-06-10 2000-02-22 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of cytokines
US6030776A (en) * 1990-06-11 2000-02-29 Nexstar Pharmaceuticals, Inc. Parallel SELEX
US6048698A (en) * 1994-09-20 2000-04-11 Nexstar Pharmaceuticals, Inc. Parallel SELEX™
US6083696A (en) * 1990-06-11 2000-07-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands exponential enrichment: blended selex
US6100035A (en) * 1998-07-14 2000-08-08 Cistem Molecular Corporation Method of identifying cis acting nucleic acid elements
US6114120A (en) * 1995-05-03 2000-09-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US6124449A (en) * 1990-06-11 2000-09-26 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US6127119A (en) * 1990-06-11 2000-10-03 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US6140490A (en) * 1996-02-01 2000-10-31 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of complement system proteins
US6171795B1 (en) 1999-07-29 2001-01-09 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands to CD40ligand
US6177557B1 (en) 1990-06-11 2001-01-23 Nexstar Pharmaceuticals, Inc. High affinity ligands of basic fibroblast growth factor and thrombin
US6183967B1 (en) 1995-06-07 2001-02-06 Nexstar Pharmaceuticals Nucleic acid ligand inhibitors to DNA polymerases
US6207816B1 (en) 1995-06-02 2001-03-27 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to growth factors
US6229002B1 (en) 1995-06-07 2001-05-08 Nexstar Pharmaceuticlas, Inc. Platelet derived growth factor (PDGF) nucleic acid ligand complexes
US6232071B1 (en) 1990-06-11 2001-05-15 Gilead Sciences, Inc. Tenascin-C nucleic acid ligands
US6261783B1 (en) 1997-12-15 2001-07-17 Gilead Sciences, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US6261774B1 (en) 1990-06-11 2001-07-17 Gilead Sciences, Inc. Truncation selex method
US6280943B1 (en) 1999-06-17 2001-08-28 Gilead Sciences, Inc. 2′-fluoropyrimidine anti-calf intestinal phosphatase nucleic acid ligands
US6280932B1 (en) 1990-06-11 2001-08-28 Gilead Sciences, Inc. High affinity nucleic acid ligands to lectins
US6329145B1 (en) 1999-02-09 2001-12-11 Gilead Science, Inc. Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligand
US6331394B1 (en) 1991-06-10 2001-12-18 Gilead Sciences, Inc. Nucleic acid ligands to integrins
US6344321B1 (en) 1990-06-11 2002-02-05 Gilead Sciences, Inc. Nucleic acid ligands which bind to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor c-met
US6346611B1 (en) 1990-06-11 2002-02-12 Gilead Sciences, Inc. High affinity TGfβ nucleic acid ligands and inhibitors
US6376190B1 (en) 2000-09-22 2002-04-23 Somalogic, Inc. Modified SELEX processes without purified protein
US6387620B1 (en) 1999-07-28 2002-05-14 Gilead Sciences, Inc. Transcription-free selex
US6395888B1 (en) 1996-02-01 2002-05-28 Gilead Sciences, Inc. High affinity nucleic acid ligands of complement system proteins
US6458539B1 (en) 1993-09-17 2002-10-01 Somalogic, Inc. Photoselection of nucleic acid ligands
US6465188B1 (en) 1990-06-11 2002-10-15 Gilead Sciences, Inc. Nucleic acid ligand complexes
US6465189B1 (en) 1990-06-11 2002-10-15 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: blended selex
US6506887B1 (en) 1999-07-29 2003-01-14 Somalogic, Incorporated Conditional-selex
US6569620B1 (en) 1990-06-11 2003-05-27 Somalogic, Inc. Method for the automated generation of nucleic acid ligands
US6610841B1 (en) 1997-12-18 2003-08-26 Gilead Sciences, Inc. Nucleotide-based prodrugs
US6682886B1 (en) 1994-04-28 2004-01-27 Gilead Sciences, Inc. Bivalent binding molecules of 7 transmembrane G protein-coupled receptors
US6696252B2 (en) 1990-06-11 2004-02-24 Gilead Sciences, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US6699843B2 (en) 1995-06-07 2004-03-02 Gilead Sciences, Inc. Method for treatment of tumors using nucleic acid ligands to PDGF
US6716580B2 (en) 1990-06-11 2004-04-06 Somalogic, Inc. Method for the automated generation of nucleic acid ligands
US6759392B1 (en) 1990-06-11 2004-07-06 Gilead Sciences, Inc. High affinity RNA ligands of basic fibroblast growth factor
US6762290B1 (en) 1999-07-29 2004-07-13 Gilead Sciences, Inc. High affinity vascular endothelial growth factor (VEGF) receptor nucleic acid ligands and inhibitors
US6838238B1 (en) 1996-10-17 2005-01-04 Invitrogen Corporation Morphatides: novel shape and structure libraries
US6933114B2 (en) 2000-10-16 2005-08-23 Gilead Sciences, Inc. Nucleic acid ligands to the prostate specific membrane antigen
US7005260B1 (en) 2000-01-28 2006-02-28 Gilead Sciences, Inc. Tenascin-C nucleic acid ligands
US7153948B2 (en) 1994-04-25 2006-12-26 Gilead Sciences, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US7179907B2 (en) 2001-12-18 2007-02-20 Bruce Eaton Antibiotic compounds
US7538211B2 (en) 2004-02-12 2009-05-26 Archemix Corp. Aptamer therapeutics useful in the treatment of complement-related disorders
US7579450B2 (en) 2004-04-26 2009-08-25 Archemix Corp. Nucleic acid ligands specific to immunoglobulin E and their use as atopic disease therapeutics
US7803931B2 (en) 2004-02-12 2010-09-28 Archemix Corp. Aptamer therapeutics useful in the treatment of complement-related disorders
US7960102B2 (en) 2002-07-25 2011-06-14 Archemix Corp. Regulated aptamer therapeutics
US7964356B2 (en) 2007-01-16 2011-06-21 Somalogic, Inc. Method for generating aptamers with improved off-rates
US8071737B2 (en) 1995-05-04 2011-12-06 Glead Sciences, Inc. Nucleic acid ligand complexes
US8236773B2 (en) 2005-02-14 2012-08-07 Archemix Llc Aptamer therapeutics useful in the treatment of complement-related disorders
US8409795B2 (en) 2007-07-17 2013-04-02 Somalogic, Inc. Selex and photoSELEX
US8703416B2 (en) 2008-07-17 2014-04-22 Somalogic, Inc. Method for purification and identification of sperm cells
US8853376B2 (en) 2002-11-21 2014-10-07 Archemix Llc Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics
US8975026B2 (en) 2007-01-16 2015-03-10 Somalogic, Inc. Method for generating aptamers with improved off-rates
US9303262B2 (en) 2002-09-17 2016-04-05 Archemix Llc Methods for identifying aptamer regulators

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0171142A1 (en) * 1984-05-25 1986-02-12 ZymoGenetics, Inc. Methods for producing proteins and transformed cells, and DNA constructs for correcting host cell deficiencies and their preparation and use
JPS6328386A (en) * 1986-07-21 1988-02-06 Asahi Chem Ind Co Ltd Cell cultivation method
US4743679A (en) * 1986-02-24 1988-05-10 Creative Biomolecules, Inc. Process for producing human epidermal growth factor and analogs thereof
US4783412A (en) * 1983-07-05 1988-11-08 Chiron Corporation Hybrid DNA synthesis of epidermal growth factor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4783412A (en) * 1983-07-05 1988-11-08 Chiron Corporation Hybrid DNA synthesis of epidermal growth factor
EP0171142A1 (en) * 1984-05-25 1986-02-12 ZymoGenetics, Inc. Methods for producing proteins and transformed cells, and DNA constructs for correcting host cell deficiencies and their preparation and use
US4743679A (en) * 1986-02-24 1988-05-10 Creative Biomolecules, Inc. Process for producing human epidermal growth factor and analogs thereof
JPS6328386A (en) * 1986-07-21 1988-02-06 Asahi Chem Ind Co Ltd Cell cultivation method

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BIOLOGICAL ABSTRACTS, Volume 84, No. 5, issued 1 September 1987, (OVE et al.), "Isolation of an autocrine growth factor from hepatoma HTC-SR cells". See page 614, column 2, the Abstract No. 47733, J. CELL. PHYSIOL., 1987, 131(2):165-174. *
CELL, Volume 11, issued May 1977, (WIGLER et al.), "Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells". See pages 223-232. *
CHEMICAL ABSTRACTS, Volume 104, No. 25, issued 23 June 1986, (KAWASAKI et al.), "Methods for producing proteins and transformed cells, and DNA constructs for correcting host cell deficiencies and their use". See page 174, column 1, the Abstract No. 220140b; & EP,A, 171142, issued 25 May 1984. *
CHEMICAL ABSTRACTS, Volume 109, No. 5, issued 1 August 1988, (ITO et al.), "Transforming growth factor-beta, its cDNA cloning and use in promoting cellular growth in tissue culture". See page 510, column 2, the Abstract No. 36654z; & JP,A,63 028 386, issued 06 February 1988. *
EXPERIMENTAL CELL RESEARCH, Volume 134, issued 1981, (PHILLIPS et al.), "Growth regulation of W138 cells in a serum-free medium". See pages 297-302. *
PROCEEDINGS NATIONAL ACADEMY OF SCIENCES (USA), Volume 79, issued January 1982, (KAPLAN et al.), "Transforming growth factor(s) production enables cells to grow in the absence of serum: An autocrine system". See pages 485-489. *
PROCEEDINGS NATIONAL ACADEMY OF SCIENCES (USA), Volume 82, issued April 1985, (SUTHERLAND et al.), "Transformation of human cells by DNAs ineffective in transformation of NIH 3T3 cells". See pages 2399-2403. *
SCIENCE, Volume 235, issued 16 January 1987, (STERN et al.), "Construction of a novel oncogene based on synthetic sequences encoding epidermal growth factor". See entire document. *

Cited By (188)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5427908A (en) * 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
US5580717A (en) * 1990-05-01 1996-12-03 Affymax Technologies N.V. Recombinant library screening methods
US6184364B1 (en) 1990-06-11 2001-02-06 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands containing modified nucleotides
US7368236B2 (en) 1990-06-11 2008-05-06 Gilead Sciences, Inc. Methods of producing nucleic acid ligands
US7196069B2 (en) 1990-06-11 2007-03-27 Gilead Sciences, Inc. High affinity RNA ligands of basic fibroblast growth factor
US5503978A (en) * 1990-06-11 1996-04-02 University Research Corporation Method for identification of high affinity DNA ligands of HIV-1 reverse transcriptase
US5527894A (en) * 1990-06-11 1996-06-18 Nexstar Pharmacueticals, Inc. Ligands of HIV-1 tat protein
US5543293A (en) * 1990-06-11 1996-08-06 Nexstar Pharmaceuticals, Inc. DNA ligands of thrombin
US5567588A (en) * 1990-06-11 1996-10-22 University Research Corporation Systematic evolution of ligands by exponential enrichment: Solution SELEX
US5580737A (en) * 1990-06-11 1996-12-03 Nexstar Pharmaceuticals, Inc. High-affinity nucleic acid ligands that discriminate between theophylline and caffeine
US7399752B2 (en) 1990-06-11 2008-07-15 Gilead Science, Inc. High affinity nucleic acid ligands to lectins
US5587468A (en) * 1990-06-11 1996-12-24 University Research Corporation High affinity nucleic acid ligands to HIV integrase
US5595877A (en) * 1990-06-11 1997-01-21 Nexstar Pharmaceuticals, Inc. Methods of producing nucleic acid ligands
US5629155A (en) * 1990-06-11 1997-05-13 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to immunoglobulin E (IgE)
US5635615A (en) * 1990-06-11 1997-06-03 Nexstar Pharmaceuticals, Inc. High affinity HIV nucleocapsid nucleic acid ligands
US5637461A (en) * 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. Ligands of HIV-1 TAT protein
US5637682A (en) * 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to the tachykinin substance P
US5637459A (en) * 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chimeric selex
US5639868A (en) * 1990-06-11 1997-06-17 Nexstar Pharmaceuticals, Inc. High-affinity RNA ligands for basic fibroblast growth factor
US5641629A (en) * 1990-06-11 1997-06-24 Nexstar Pharmacueticals Inc Spectroscopically detectable nucleic acid ligands
US5648214A (en) * 1990-06-11 1997-07-15 University Research Corporation High-affinity oligonucleotide ligands to the tachykinin substance P
US5654151A (en) * 1990-06-11 1997-08-05 Nexstar Pharmaceuticals, Inc. High affinity HIV Nucleocapsid nucleic acid ligands
US5660985A (en) * 1990-06-11 1997-08-26 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands containing modified nucleotides
US5668264A (en) * 1990-06-11 1997-09-16 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US5670637A (en) * 1990-06-11 1997-09-23 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands
US5674685A (en) * 1990-06-11 1997-10-07 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US5683867A (en) * 1990-06-11 1997-11-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: blended SELEX
US5686592A (en) * 1990-06-11 1997-11-11 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to immunoglobulin E (IgE)
US5688935A (en) * 1990-06-11 1997-11-18 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US5693502A (en) * 1990-06-11 1997-12-02 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5696249A (en) * 1990-06-11 1997-12-09 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands
US5705337A (en) * 1990-06-11 1998-01-06 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-SELEX
US5707796A (en) * 1990-06-11 1998-01-13 Nexstar Pharmaceuticals, Inc. Method for selecting nucleic acids on the basis of structure
US5712375A (en) * 1990-06-11 1998-01-27 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US7176295B2 (en) 1990-06-11 2007-02-13 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: blended SELEX
US6933116B2 (en) 1990-06-11 2005-08-23 Gilead Sciences, Inc. Nucleic acid ligand binding site identification
US5723289A (en) * 1990-06-11 1998-03-03 Nexstar Pharmaceuticals, Inc. Parallel selex
US6855496B2 (en) 1990-06-11 2005-02-15 Gilead Sciences, Inc. Truncation SELEX method
US5726017A (en) * 1990-06-11 1998-03-10 Nexstar Pharmaceuticals, Inc. High affinity HIV-1 gag nucleic acid ligands
US5731424A (en) * 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US5731144A (en) * 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands
US5734034A (en) * 1990-06-11 1998-03-31 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors of human neutrophil elastase
US6759392B1 (en) 1990-06-11 2004-07-06 Gilead Sciences, Inc. High affinity RNA ligands of basic fibroblast growth factor
US5750342A (en) * 1990-06-11 1998-05-12 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US5756287A (en) * 1990-06-11 1998-05-26 Nexstar Pharmaceuticals, Inc. High affinity HIV integrase inhibitors
US5763173A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5763566A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue SELEX
US5763177A (en) * 1990-06-11 1998-06-09 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex
US5766853A (en) * 1990-06-11 1998-06-16 Nexstar Pharmaceuticals, Inc. Method for identification of high affinity nucleic acid ligands to selectins
US6716580B2 (en) 1990-06-11 2004-04-06 Somalogic, Inc. Method for the automated generation of nucleic acid ligands
US5773598A (en) * 1990-06-11 1998-06-30 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chimeric selex
US5780228A (en) * 1990-06-11 1998-07-14 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands to lectins
US5786462A (en) * 1990-06-11 1998-07-28 Nexstar Pharmaceuticals, Inc. High affinity ssDNA ligands of HIV-1 reverse transcriptase
US5789163A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Enzyme linked oligonucleotide assays (ELONAS)
US5789157A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5795721A (en) * 1990-06-11 1998-08-18 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of ICP4
US6716583B2 (en) 1990-06-11 2004-04-06 Gilead Sciences, Inc. Methods of producing nucleic acid ligands
US5811533A (en) * 1990-06-11 1998-09-22 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US5817785A (en) * 1990-06-11 1998-10-06 Nexstar Pharmaceuticals, Inc. Methods of producing nucleic acid ligands
US5837456A (en) * 1990-06-11 1998-11-17 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to chorionic gonadotropin hormone and related glycoprotein hormones
US5837834A (en) * 1990-06-11 1998-11-17 Nexstar Pharmaceuticals, Inc. High affinity HKGF nucleic acid ligands and inhibitors
US5843653A (en) * 1990-06-11 1998-12-01 Nexstar Pharmaceuticals, Inc. Method for detecting a target molecule in a sample using a nucleic acid ligand
US6713616B2 (en) 1990-06-11 2004-03-30 Gilead Sciences, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US5846713A (en) * 1990-06-11 1998-12-08 Nexstar Pharmaceuticals, Inc. High affinity HKGF nucleic acid ligands and inhibitors
US5849890A (en) * 1990-06-11 1998-12-15 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to chorionic gonadotropin hormone and related glycoprotein hormones
US5853984A (en) * 1990-06-11 1998-12-29 Nexstar Pharmaceuticals, Inc. Use of nucleic acid ligands in flow cytometry
US6696252B2 (en) 1990-06-11 2004-02-24 Gilead Sciences, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US6596491B2 (en) 1990-06-11 2003-07-22 Gilead Sciences, Inc. Tenascin-C nucleic acid ligands
US5864026A (en) * 1990-06-11 1999-01-26 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5869641A (en) * 1990-06-11 1999-02-09 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of CD4
US6569620B1 (en) 1990-06-11 2003-05-27 Somalogic, Inc. Method for the automated generation of nucleic acid ligands
US5874557A (en) * 1990-06-11 1999-02-23 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand inhibitors to DNA polymerases
US5874218A (en) * 1990-06-11 1999-02-23 Nexstar Pharmaceuticals, Inc. Method for detecting a target compound in a substance using a nucleic acid ligand
US5958691A (en) * 1990-06-11 1999-09-28 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands containing modified nucleotides
US5962219A (en) * 1990-06-11 1999-10-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-selex
US5972599A (en) * 1990-06-11 1999-10-26 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of cytokines
US6544959B1 (en) 1990-06-11 2003-04-08 Gilead Sciences, Inc. High affinity nucleic acid ligands to lectins
US6482594B2 (en) 1990-06-11 2002-11-19 Somalogic, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands
US6001988A (en) * 1990-06-11 1999-12-14 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands to lectins
US6465189B1 (en) 1990-06-11 2002-10-15 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: blended selex
US6011020A (en) * 1990-06-11 2000-01-04 Nexstar Pharmaceuticals, Inc. Nucleic acid ligand complexes
US6465188B1 (en) 1990-06-11 2002-10-15 Gilead Sciences, Inc. Nucleic acid ligand complexes
US6346611B1 (en) 1990-06-11 2002-02-12 Gilead Sciences, Inc. High affinity TGfβ nucleic acid ligands and inhibitors
US6344321B1 (en) 1990-06-11 2002-02-05 Gilead Sciences, Inc. Nucleic acid ligands which bind to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor c-met
US6030776A (en) * 1990-06-11 2000-02-29 Nexstar Pharmaceuticals, Inc. Parallel SELEX
US6331398B1 (en) 1990-06-11 2001-12-18 Gilead Sciences, Inc. Nucleic acid ligands
US6083696A (en) * 1990-06-11 2000-07-04 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands exponential enrichment: blended selex
US6300074B1 (en) 1990-06-11 2001-10-09 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: Chemi-SELEX
US6110900A (en) * 1990-06-11 2000-08-29 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands
US6291184B1 (en) 1990-06-11 2001-09-18 Somalogic, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex
US6124449A (en) * 1990-06-11 2000-09-26 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US6127119A (en) * 1990-06-11 2000-10-03 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands of tissue target
US6280932B1 (en) 1990-06-11 2001-08-28 Gilead Sciences, Inc. High affinity nucleic acid ligands to lectins
US6261774B1 (en) 1990-06-11 2001-07-17 Gilead Sciences, Inc. Truncation selex method
US6344318B1 (en) 1990-06-11 2002-02-05 Gilead Sciences, Inc. Methods of producing nucleic acid ligands
US6232071B1 (en) 1990-06-11 2001-05-15 Gilead Sciences, Inc. Tenascin-C nucleic acid ligands
US6177557B1 (en) 1990-06-11 2001-01-23 Nexstar Pharmaceuticals, Inc. High affinity ligands of basic fibroblast growth factor and thrombin
US5270163A (en) * 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands
US5432018A (en) * 1990-06-20 1995-07-11 Affymax Technologies N.V. Peptide library and screening systems
US7553617B1 (en) 1990-06-20 2009-06-30 Affymax, Inc. Peptide library and screening systems
US5723286A (en) * 1990-06-20 1998-03-03 Affymax Technologies N.V. Peptide library and screening systems
US6194550B1 (en) * 1990-08-02 2001-02-27 Larry Gold Systematic polypeptide evolution by reverse translation
US5843701A (en) * 1990-08-02 1998-12-01 Nexstar Pharmaceticals, Inc. Systematic polypeptide evolution by reverse translation
US6028186A (en) * 1991-06-10 2000-02-22 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of cytokines
US6331394B1 (en) 1991-06-10 2001-12-18 Gilead Sciences, Inc. Nucleic acid ligands to integrins
US7094535B2 (en) 1991-06-10 2006-08-22 Gilead Sciences, Inc. Nucleic acid ligands to integrins
US6156511A (en) * 1991-10-16 2000-12-05 Affymax Technologies N.V. Peptide library and screening method
US5733731A (en) * 1991-10-16 1998-03-31 Affymax Technologies N.V. Peptide library and screening method
US5498530A (en) * 1991-10-16 1996-03-12 Affymax Technologies, N.V. Peptide library and screening method
US5397706A (en) * 1991-11-06 1995-03-14 Correa; Paulo N. Serum-free basal and culture medium for hematopoietic and leukemia cells
US5719273A (en) * 1993-06-14 1998-02-17 Nexstar Pharmaceuticals, Inc. Palladium catalyzed nucleoside modifications methods using nucleophiles and carbon monoxide
US5998142A (en) * 1993-09-08 1999-12-07 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-SELEX
US6458539B1 (en) 1993-09-17 2002-10-01 Somalogic, Inc. Photoselection of nucleic acid ligands
US6319713B1 (en) * 1994-02-17 2001-11-20 Maxygen, Inc. Methods and compositions for polypeptide engineering
US6355484B1 (en) 1994-02-17 2002-03-12 Maxygen, Inc. Methods and compositions for polypeptides engineering
US7153948B2 (en) 1994-04-25 2006-12-26 Gilead Sciences, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US6682886B1 (en) 1994-04-28 2004-01-27 Gilead Sciences, Inc. Bivalent binding molecules of 7 transmembrane G protein-coupled receptors
US7087735B2 (en) 1994-04-28 2006-08-08 Gilead Sciences, Inc. Bivalent binding molecules of 7 transmembrane G protein-coupled receptors
US6048698A (en) * 1994-09-20 2000-04-11 Nexstar Pharmaceuticals, Inc. Parallel SELEX™
US6335160B1 (en) * 1995-02-17 2002-01-01 Maxygen, Inc. Methods and compositions for polypeptide engineering
US6013443A (en) * 1995-05-03 2000-01-11 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue SELEX
US6114120A (en) * 1995-05-03 2000-09-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US6376474B1 (en) 1995-05-03 2002-04-23 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: tissue SELEX
US6613526B2 (en) 1995-05-03 2003-09-02 Gilead Sciences, Inc. Systematic evolution of ligands by exponential enrichment: tissue selex
US5859228A (en) * 1995-05-04 1999-01-12 Nexstar Pharmaceuticals, Inc. Vascular endothelial growth factor (VEGF) nucleic acid ligand complexes
US8071737B2 (en) 1995-05-04 2011-12-06 Glead Sciences, Inc. Nucleic acid ligand complexes
US6207816B1 (en) 1995-06-02 2001-03-27 Nexstar Pharmaceuticals, Inc. High affinity oligonucleotide ligands to growth factors
US6020130A (en) * 1995-06-07 2000-02-01 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands that bind to and inhibit DNA polymerases
US7879993B2 (en) 1995-06-07 2011-02-01 Gilead Sciences, Inc. Platelet derived growth factor (PDGF) nucleic acid ligand complexes
US6229002B1 (en) 1995-06-07 2001-05-08 Nexstar Pharmaceuticlas, Inc. Platelet derived growth factor (PDGF) nucleic acid ligand complexes
US7141375B2 (en) 1995-06-07 2006-11-28 Gilead Sciences, Inc. Methods and compositions for treatment of tumors using nucleic acid ligands to platelet-derived growth factor
US5797870A (en) * 1995-06-07 1998-08-25 Indiana University Foundation Pericardial delivery of therapeutic and diagnostic agents
US6699843B2 (en) 1995-06-07 2004-03-02 Gilead Sciences, Inc. Method for treatment of tumors using nucleic acid ligands to PDGF
US6582918B2 (en) 1995-06-07 2003-06-24 Gilead Sciences, Inc. Platelet derived growth factor (PDGF) nucleic acid ligand complexes
US5723594A (en) * 1995-06-07 1998-03-03 Nexstar Pharmaceuticals, Inc. High affinity PDGF nucleic acid ligands
US6183967B1 (en) 1995-06-07 2001-02-06 Nexstar Pharmaceuticals Nucleic acid ligand inhibitors to DNA polymerases
US6395888B1 (en) 1996-02-01 2002-05-28 Gilead Sciences, Inc. High affinity nucleic acid ligands of complement system proteins
US6566343B2 (en) 1996-02-01 2003-05-20 Gilead Sciences, Inc. High affinity nucleic acid ligands of complement system proteins
US7964572B2 (en) 1996-02-01 2011-06-21 Gilead Sciences, Inc. High affinity nucleic acid ligands of complement system proteins
US6140490A (en) * 1996-02-01 2000-10-31 Nexstar Pharmaceuticals, Inc. High affinity nucleic acid ligands of complement system proteins
US6838238B1 (en) 1996-10-17 2005-01-04 Invitrogen Corporation Morphatides: novel shape and structure libraries
US6303344B1 (en) 1996-12-18 2001-10-16 Maxygen, Inc. Methods and compositions for polypeptide engineering
WO1998027230A1 (en) * 1996-12-18 1998-06-25 Maxygen, Inc. Methods and compositions for polypeptide engineering
EP1149904A1 (en) * 1996-12-18 2001-10-31 Maxygen, Inc. Methods and compositions for polypeptide engineering
US5871924A (en) * 1997-01-27 1999-02-16 Nexstar Pharmaceuticals, Inc. Method for the production of ligands capable of facilitating aminoacyl-RNA synthesis
US5861254A (en) * 1997-01-31 1999-01-19 Nexstar Pharmaceuticals, Inc. Flow cell SELEX
US6261783B1 (en) 1997-12-15 2001-07-17 Gilead Sciences, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US6531286B2 (en) 1997-12-15 2003-03-11 Gilead Sciences, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US7939654B2 (en) 1997-12-16 2011-05-10 Gilead Sciences, Inc. Platelet derived growth factor (PDGF) nucleic acid ligand complexes
US6610841B1 (en) 1997-12-18 2003-08-26 Gilead Sciences, Inc. Nucleotide-based prodrugs
US6001577A (en) * 1998-06-08 1999-12-14 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex
US6100035A (en) * 1998-07-14 2000-08-08 Cistem Molecular Corporation Method of identifying cis acting nucleic acid elements
US6413723B1 (en) 1998-07-14 2002-07-02 Cistem Molecular Corporation Methods and compositions for identifying nucleic acids containing cis acting elements
US6177555B1 (en) 1998-09-18 2001-01-23 Nexstar Pharmaceuticals, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US5989823A (en) * 1998-09-18 1999-11-23 Nexstar Pharmaceuticals, Inc. Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
US7629151B2 (en) 1999-01-19 2009-12-08 Somalogic, Inc. Method and apparatus for the automated generation of nucleic acid ligands
US7258980B2 (en) 1999-02-09 2007-08-21 Gilead Sciences, Inc. Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligands
US6329145B1 (en) 1999-02-09 2001-12-11 Gilead Science, Inc. Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligand
US6670132B2 (en) 1999-02-09 2003-12-30 Gilead Sciences, Inc. Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligand
US6673553B2 (en) 1999-06-17 2004-01-06 Gilead Sciences, Inc. 2′-fluoropyrimidine anti-calf intestinal phosphatase nucleic acid ligands
US6280943B1 (en) 1999-06-17 2001-08-28 Gilead Sciences, Inc. 2′-fluoropyrimidine anti-calf intestinal phosphatase nucleic acid ligands
US6387635B1 (en) 1999-06-17 2002-05-14 Gilead Sciences, Inc. 2′-fluoropyrimidine anti-calf intestinal phosphatase nucleic acid ligands
US6387620B1 (en) 1999-07-28 2002-05-14 Gilead Sciences, Inc. Transcription-free selex
US6762290B1 (en) 1999-07-29 2004-07-13 Gilead Sciences, Inc. High affinity vascular endothelial growth factor (VEGF) receptor nucleic acid ligands and inhibitors
US6506887B1 (en) 1999-07-29 2003-01-14 Somalogic, Incorporated Conditional-selex
US6706482B2 (en) 1999-07-29 2004-03-16 Somalogic, Inc. Conditional-selex
US6171795B1 (en) 1999-07-29 2001-01-09 Nexstar Pharmaceuticals, Inc. Nucleic acid ligands to CD40ligand
US7005260B1 (en) 2000-01-28 2006-02-28 Gilead Sciences, Inc. Tenascin-C nucleic acid ligands
US6730482B2 (en) 2000-09-22 2004-05-04 Somalogic, Inc. Modified SELEX processes without purified protein
US6376190B1 (en) 2000-09-22 2002-04-23 Somalogic, Inc. Modified SELEX processes without purified protein
US6933114B2 (en) 2000-10-16 2005-08-23 Gilead Sciences, Inc. Nucleic acid ligands to the prostate specific membrane antigen
US7179907B2 (en) 2001-12-18 2007-02-20 Bruce Eaton Antibiotic compounds
US7960102B2 (en) 2002-07-25 2011-06-14 Archemix Corp. Regulated aptamer therapeutics
US9303262B2 (en) 2002-09-17 2016-04-05 Archemix Llc Methods for identifying aptamer regulators
US8853376B2 (en) 2002-11-21 2014-10-07 Archemix Llc Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics
US7803931B2 (en) 2004-02-12 2010-09-28 Archemix Corp. Aptamer therapeutics useful in the treatment of complement-related disorders
US7579456B2 (en) 2004-02-12 2009-08-25 Archemix Corp. Aptamer therapeutics useful in the treatment of complement-related disorders
US7538211B2 (en) 2004-02-12 2009-05-26 Archemix Corp. Aptamer therapeutics useful in the treatment of complement-related disorders
US7579450B2 (en) 2004-04-26 2009-08-25 Archemix Corp. Nucleic acid ligands specific to immunoglobulin E and their use as atopic disease therapeutics
US8436164B2 (en) 2005-02-14 2013-05-07 Archemix Llc Aptamer therapeutics useful in the treatment of complement-related disorders
US8236773B2 (en) 2005-02-14 2012-08-07 Archemix Llc Aptamer therapeutics useful in the treatment of complement-related disorders
US9617546B2 (en) 2005-02-14 2017-04-11 Archemix Llc Aptamer therapeutics useful in the treatment of complement-related disorders
US8946184B2 (en) 2005-02-14 2015-02-03 Archemix Llc Aptamer therapeutics useful in the treatment of complement-related disorders
US8975026B2 (en) 2007-01-16 2015-03-10 Somalogic, Inc. Method for generating aptamers with improved off-rates
US9382533B2 (en) 2007-01-16 2016-07-05 Somalogic, Inc. Method for generating aptamers with improved off-rates
US7964356B2 (en) 2007-01-16 2011-06-21 Somalogic, Inc. Method for generating aptamers with improved off-rates
US8409795B2 (en) 2007-07-17 2013-04-02 Somalogic, Inc. Selex and photoSELEX
US8703416B2 (en) 2008-07-17 2014-04-22 Somalogic, Inc. Method for purification and identification of sperm cells

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