Richard H Metz

US Patent:

6479292, Nov 12, 2002

Filed:

Aug 25, 2000

Appl. No.:

09/645889

Inventors:

Richard A. Metz - Lawrenceville NJ
Bruce L. Frank - Langhorne PA
Debra M. Walther - Langhorne PA

Assignee:

ValiGen (US), Inc. - New York NY

International Classification:

C12N 1582

US Classification:

435468, 435410, 435469, 435470, 514 44, 536 231, 536 266

Abstract:

The invention concerns the introduction of predetermined genetic changes in target genes of a living cell by introducing an oligodeoxynucleotide encoding the predetermined change. The oligodeoxynucleotides are effective in animal, plant and bacterial cells. Specific end modifications that greatly increase the effectiveness of the oligodeoxynucleotides in bacteria are described. Surprisingly, unmodified oligodeoxynucleotides can be as effective in mammalian cells, including in vivo hepatocytes, as the modified nucleotides and can be as effective or more effective than chimeric oligonucleotides that consist of a mixture of deoxynucleotides and 2â-O-methyl ribonucleotides.

US Patent:

6586184, Jul 1, 2003

Filed:

Apr 3, 2001

Appl. No.:

09/825124

Inventors:

Ramesh Kumar - Pennington NJ
Richard A. Metz - Lawrenceville NJ

Assignee:

ValiGen (U.S.), Inc. - New York NY

International Classification:

C12Q 168

US Classification:

435 6, 536 221, 536 231, 435440, 435471, 435485, 435488, 435243, 4352521, 4352523, 4353201

Abstract:

The invention is based on the discovery that recombinagenic oligonucleobases are active in prokaryotic cells that contain a strand transfer activity (RecA) and mismatch repair activity (MutS). Using this system a type of Duplex Mutational Vector termed a Heteroduplex Mutational Vector, was shown to be more active in prokaryotic cells than the types of mutational vectors heretofore tested. Further improvements in activity were obtained by replacing the tetrathymidine linker by a nuclease resistant oligonucleotide, such as tetra-2â-O-methyl-uridine, to link the two strands of the recombinagenic oligonucleobase and removing the DNA-containing intervening segment. The claims concern Duplex Mutational Vectors that contain the above improvements. In an alternative embodiment the claims concern the use of Duplex Mutational Vectors in prokaryotic cells.

US Patent:

6929917, Aug 16, 2005

Filed:

Nov 18, 2002

Appl. No.:

10/298850

Inventors:

Richard Metz - Lawrenceville NJ, US
Mike DiCola - Flemington NJ, US
R. Michael Blaese - New Hope PA, US

Assignee:

PreGentis - New Town PA

International Classification:

C12N015/09
C12N015/00
C12N021/00
C12N015/85
C12Q001/68

US Classification:

435 6, 435468, 435471, 435 691, 435 697, 435 701, 435 711, 435440, 435325, 4352521, 4352542

Abstract:

The invention concerns a new method of detecting a rare product of a directed genetic alteration of a cultured cell. The method is applicable to any method of making the alteration provided that a pair of closely linked alterations can be made. The method consists of sequentially using allele specific polymerase chain reaction (PCR) to preferentially amplify sequences containing one of the two linked alterations coupled with a second method that detects the second change in the PCR product. The second method can be restriction digestion, traditional sequencing or pyro-sequencing. Experiments indicate that alterations as rare as one correctly altered copy in 10,000 cells can be detected.

US Patent:

7060500, Jun 13, 2006

Filed:

Nov 12, 2002

Appl. No.:

10/292856

Inventors:

Richard A. Metz - Lawrenceville NJ, US
Bruce L. Frank - Langhorne PA, US
Debra M. Walther - Langhorne PA, US

International Classification:

C12N 15/63
C12N 15/88
C12N 15/87
A01N 43/04
C07H 21/02

US Classification:

435458, 435455, 435463, 435490, 514 44, 536 231, 536 266

Abstract:

The invention concerns the introduction of predetermined genetic changes in target genes of a living cell by introducing an oligodeoxynucleotide encoding the predetermined change. The oligodeoxynucleotides are effective in animal, plant and bacterial cells. Specific end modifications that greatly increase the effectiveness of the oligodeoxynucleotides in bacteria are described. Surprisingly, unmodified oligodeoxynucleotides can be as effective in mammalian cells, including in vivo hepatocytes, as the modified nucleotides and can be as effective or more effective than chimeric oligonucleotides that consist of a mixture of deoxynucleotides and 2′-O-methyl ribonucleotides.

US Patent:

8058416, Nov 15, 2011

Filed:

Nov 18, 2008

Appl. No.:

12/273296

Inventors:

George C. Prendergast - Penn Valley PA, US
Richard Metz - Pennington NJ, US

Assignee:

Lankenau Institute for Medical Research - Wynnewood PA

International Classification:

C07H 21/02
C07H 21/04

US Classification:

536 231

Abstract:

The nucleotide and amino acid sequences of indoleamine 2,3-dioxygenase-2 (IDO2) and methods of use thereof are provided.

US Patent:

8436151, May 7, 2013

Filed:

Nov 4, 2011

Appl. No.:

13/289597

Inventors:

George C. Prendergast - Penn Valley PA, US
Richard Metz - Pennington NJ, US

Assignee:

Lankenau Institute for Medical Research - Wynnewood PA

International Classification:

C07K 16/40

US Classification:

53038826

Abstract:

The nucleotide and amino acid sequences of indoleamine 2,3-dioxygenase-2 (IDO2) and methods of use thereof are provided.

US Patent:

20030229910, Dec 11, 2003

Filed:

Apr 17, 2003

Appl. No.:

10/417964

Inventors:

Richard Metz - Lawrenceville NJ, US
R. Blaese - New Hope PA, US

International Classification:

A01K067/027
A61K048/00

US Classification:

800/015000, 424/093210

Abstract:

A method for generating cattle resistant to Bovine Spongioform Encephalopathy through targeted alterations in the PrP gene is disclosed. The PrP gene of a cultured cells is altered to prevent its translation or to encode a dominant disease-resistant form of the protein, and the nucleus of the altered cell is used to clone a founder animal. In one embodiment, a single-stranded DNA fragment containing the alteration is used in single-stranded short fragment homologous replacement to alter the PrP gene.

US Patent:

20130227719, Aug 29, 2013

Filed:

Mar 5, 2013

Appl. No.:

13/785033

Inventors:

Lankenau Institute for Medical Research - , US
Richard Metz - Pennington NJ, US

Assignee:

LANKENAU INSTITUTE FOR MEDICAL RESEARCH - Wynnewood PA

International Classification:

C12N 9/00
C12Q 1/26
A01K 67/027

US Classification:

800 18, 536 232, 435189, 435 25

Abstract:

The nucleotide and amino acid sequences of indoleamine 2,3-dioxygenase-2 (IDO2) and methods of use thereof are provided.