LAWRENCE LOEB, M.D.
Osteopathic Medicine at 36 Pl, Bellevue, WA

6451571, Sep 17, 2002

Mar 17, 1999

09/270956

Lawrence A. Loeb - Bellevue WA
Margaret E. Black - Bothell WA

University of Washington - Seattle WA

C12N 900

435194, 435183, 435193

The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution upstream from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within another aspect, one of the mutations is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.

6602695, Aug 5, 2003

Oct 16, 2001

09/981194

Premal H. Patel - Bellevue WA
Lawrence A. Loeb - Bellevue WA

University of Washington - Seattle WA

C12N 912

435194, 536 232, 530300

This invention provides a DNA polymerase that is a mutant form of a naturally occurring DNA polymerase, of which one or more amino acids in the active site are mutated. The DNA polymerase mutant of this invention is characterized by altered fidelity or altered enzymatic activity in comparison with the naturally occurring DNA polymerase. For example, the DNA polymerase mutant provides increased enzymatic activity, altered dNTP/rNTP specificity, or enhanced fidelity. In one aspect of the invention, the naturally occurring DNA polymerase comprises an amino acid sequence motif: AspTyrSerGlnIleGluLeuArg in the active site. In another aspect of the invention, the naturally occurring DNA polymerase comprises an amino acid sequence motif: LeuLeuValAlaLeuAspTyrSerGlnIleGluLeuArg in the active site. The mutant DNA polymerase has been altered in the active site of the naturally occurring DNA polymerase to contain either (a) two or more amino acid substitutions in the amino acid sequence motif, or (b) a substitution of an amino acid other than Glu in the amino acid sequence motif.

5824469, Oct 20, 1998

Sep 30, 1994

8/316415

Marshall S. Horwitz - Bellevue WA
Lawrence A. Loeb - Bellevue WA

University of Washington - Seattle WA

C12Q 168, C12N 1511, C12N 1510, C12P 1934

435 6

A method of obtaining an oligonucleotide capable of carrying out a predetermined biological function. A heterogeneous pool of oligonucleotides, x+y+z nucleotides in length, is first generated. Each oligonucleotide has a 5' randomized sequence, x nucleotides in length, a central preselected sequence, y nucleotides in length, and a 3' randomized sequence, z nucleotides in length. The resulting heterogeneous pool contains nucleic acid sequences representing a random sampling of the 4. sup. x+z possible sequences for oligonucleotides of the stated length. A random sampling of the heterogeneous pool of oligonucleotides is introduced into a population of cells that do not exhibit the predetermined biological function. The population of engineered cells is then screened for a subpopulation of cells exhibiting the predetermined biological function. From that subpopulation of cells is isolated an oligonucleotide containing the preselected sequence and capable of carrying out the predetermined biological function.

6329178, Dec 11, 2001

Jan 14, 2000

9/484114

Premal H. Patel - Bellevue WA
Lawrence A. Loeb - Bellevue WA

University of Washington - Seattle WA

C12P 1934

435 911

This invention provides a DNA polymerase that is a mutant form of a naturally occurring DNA polymerase, of which one or more amino acids in the active site are mutated. The DNA polymerase mutant of this invention is characterized by altered fidelity or altered enzymatic activity in comparison with the naturally occurring DNA polymerase. For example, the DNA polymerase mutant provides increased enzymatic activity, altered dNTP/rNTP specificity, or enhanced fidelity. In one aspect of the invention, the naturally occurring DNA polymerase comprises an amino acid sequence motif: AspTyrSerGlnIleGluLeuArg in the active site. In another aspect of the invention, the naturally occurring DNA polymerase comprises an amino acid sequence motif: LeuLeuVa1AlaLeuAspTyrSerGlnIleGluLeuArg in the active site. The mutant DNA polymerase has been altered in the active site of the naturally occurring DNA polymerase to contain either (a) two or more amino acid substitutions in the amino acid sequence motif, or (b) a substitution of an amino acid other than Glu in the amino acid sequence motif.

2007011, May 17, 2007

Oct 18, 2006

11/582372

Dipak Dube - Seattle WA, US
Marshall Horwitz - Medina WA, US
Lawrence Loeb - Bellevue WA, US

C12Q 1/68, G06F 19/00

435006000, 702020000

A method of obtaining an oligonucleotide capable of carrying out a predetermined biological function. A heterogeneous pool of oligonucleotides, x+y+z nucleotides in length, is first generated. Each oligonucleotide has a 5′ randomized sequence, x nucleotides in length, a central preselected sequence, y nucleotides in length, and a 3′ randomized sequence, z nucleotides in length. The resulting heterogeneous pool contains nucleic acid sequences representing a random sampling of the 4possible sequences for oligonucleotides of the stated length. A random sampling of the heterogeneous pool of oligonucleotides is introduced Into a population of cells that do not exhibit the predetermined biological function. The population of engineered cells Is then screened for a subpopulation of cells exhibiting the predetermined biological function. From that subpopulation of cells Is Isolated an oligonucleotide containing the preselected sequence and capable of carrying out the predetermined biological function.

2006000, Jan 12, 2006

Jan 15, 2004

10/757590

Dipak Dube - Seattle WA, US
Marshall Horwitz - Meding WA, US
Lawrence Loeb - Bellevue WA, US

University of Washington - Seattle WA

C12Q 1/68, C12P 19/34

435006000, 435091200

A method of obtaining an oligonucleotide capable of carrying out a predetermined biological function. A heterogeneous pool of oligonucleotides, x+y+z nucleotides in length, is first generated. Each oligonucleotide has a 5′ randomized sequence, x nucleotides in length, a central preselected sequence, y nucleotides in length, and a 3′ randomized sequence, z nucleotides in length. The resulting heterogeneous pool contains nucleic acid sequences representing a random sampling of the 4possible sequences for oligonucleotides of the stated length. A random sampling of the heterogeneous pool of oligonucleotides is introduced into a population of cells that do not exhibit the predetermined biological function. The population of engineered cells is then screened for a subpopulation of cells exhibiting the predetermined biological function. From that subpopulation of cells is isolated an oligonucleotide containing the preselected sequence and capable of carrying out the predetermined biological function.

2003022, Dec 4, 2003

Dec 3, 2002

10/308192

Lawrence Loeb - Bellevue WA, US
Werner Geurtsen - Hannover, DE

A61K048/00, A61K038/17, C12N009/64

514/012000, 514/044000, 435/226000

Novel thymidylate synthase (TS mutants) are disclosed differing from human wild type thymidylate synthase in single, double, or multiple mutations, which show enhanced resistant to TS-inhibiting drugs like 5-fluorouracil or 5-fluoro-2-deoxyuridinemonophosphate. All these mutants can be used for the protection of normal human cell populations against the toxic manifestation of analogs that inhibited TD.

5877010, Mar 2, 1999

May 2, 1995

8/432871

Lawrence A. Loeb - Bellevue WA
Margaret E. Black - Bothell WA

University of Washington - Seattle WA

C12N 1563, C12N 510, C12N 100, C12N 1511

4353201

The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution upstream from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within another aspect, one of the mutations is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.

2005018, Aug 25, 2005

Apr 4, 2005

11/098796

Lawrence Loeb - Bellevue WA, US
James Mullins - Seattle WA, US

University of Washington - Seattle WA

A61K048/00, C12N015/86, C12N007/00

514044000, 435235100, 435456000

The present invention is directed to the identification and use of ribonucleoside analogs to induce the mutation of an RNA virus, including BVDV, HIV and HCV, or a virus which otherwise replicates through an RNA intermediate. The increase in the mutation rate of the virus results in reduced viability of progeny generations of the virus, thereby inhibiting viral replication. In addition to these methods and related compositions, the invention provides methods and combinatorial chemistry libraries for screening ribonucleoside analogs for mutagenic potential.

5512431, Apr 30, 1996

Jun 29, 1994

8/268686

Lawrence A. Loeb - Bellevue WA
John M. Essigmann - Brookline MA

Darwin Molecular Corporation - Bothell WA

C12Q 170, C12Q 168

435 5

Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrect base pairing. Progressive mutation of the virus by such nucleoside analogs renders it non-viable.