Leo H Lin

US Patent:

46561323, Apr 7, 1987

Filed:

Mar 28, 1984

Appl. No.:

6/594250

Inventors:

Arie Ben-Bassat - Concord CA
Glenn Dorin - San Rafael CA
Keith Bauer - Oakland CA
Leo Lin - Fremont CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C12P 2100
C12N 1500

US Classification:

435 68

Abstract:

A method for improving the yield of heterologous protein such as IFN-. alpha. , IFN-. beta. , and IL-2, produced by recombinant bacteria by supplementing the nutrient medium in which the bacteria are grown with a water soluble alcohol and/or amino acid mixture during the terminal phase of the cultivation.

US Patent:

46846239, Aug 4, 1987

Filed:

Nov 26, 1985

Appl. No.:

6/801989

Inventors:

James W. Larrick - Woodside CA
Gordon M. Ringold - Palo Alto CA
David F. Mark - Danville CA
Leo S. Lin - Walnut Creek CA
Frank M. Torti - Palo Alto CA

Assignee:

The Board of Trustees of the Cetus Corporation - Emeryvile CA
Leland Stanford Junior University - Stanford CA

International Classification:

A61K 3702
A61K 3900

US Classification:

514 12

Abstract:

A method for controlling weight by suppressing the normal metabolism of adipose tissue is disclosed. Administration of tumor necrosis factor (TNF) or a pharmaceutical composition containing it results in suppression of anabolism of adipose cells.

US Patent:

47374624, Apr 12, 1988

Filed:

Jul 10, 1985

Appl. No.:

6/753717

Inventors:

David F. Mark - Hercules CA
Leo S. Lin - Fremont CA
Shi-Da Yu Lu - Oakland CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C12N 120
C12N 1500
C07H 2104

US Classification:

435253

Abstract:

A modified IFN-. beta. is provided wherein the cysteine residue at position 17 is deleted and serine is substituted therefor. DNA sequences coding for the modified protein, nucleotide primers used for the mutagenesis, appropriate cloning vectors, host organisms transformed with the vectors, methods for the production and use of the modified IFN-. beta. (IFN-. beta. sub. ser17) are also provided. The specific activity of IFN-. beta. sub. ser17 is found to be substantially the same as that of native IFN-. beta.

US Patent:

47482346, May 31, 1988

Filed:

Mar 25, 1986

Appl. No.:

6/843997

Inventors:

Glenn Dorin - San Rafael CA
Wolfgang H. Hanisch - Balmoral Heights, AU
Leo S. Lin - Walnut Creek CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C07K 312
C07K 328
A61K 4502

US Classification:

530412

Abstract:

A refractile material containing a heterologous protein is recovered from a host microorganism cell culture transformed to produce the protein. One recovery process involves disrupting the cell wall and membrane of the host cell, removing greater than 99% by weight of the salts from the disruptate, redisrupting the desalted disruptate, adding a material to the disruptate to create a density or viscosity gradient in the liquid within the disruptate, and separating the refractile material from the cellular debris by high-speed centrifugation. Another version of such a recovery process comprises the further steps of solubilizing the refractile material under reducing conditions, organically extracting the solubilized refractile material, and isolating said refractile material from the extractant. Preferably the protein is recombinant IL-2 or IFN-. beta. and the salt removal step is carried out by diafiltration.

US Patent:

44501030, May 22, 1984

Filed:

Mar 1, 1982

Appl. No.:

6/353360

Inventors:

Michael W. Konrad - Alameda CA
Leo S. Lin - Fremont CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C07G 700
C12P 2100
C12P 2102
A61K 4502

US Classification:

260112R

Abstract:

A process for recovering IFN-. beta. from transformed bacteria comprising: disrupting the cell membranes of the bacteria; solubilizing the IFN-. beta. from the disruptate into an aqueous medium with a solubilizing agent such as sodium dodecyl sulfate; extracting the IFN-. beta. from the aqueous medium with 2-butanol, 2-methyl-butanol, or mixtures thereof under conditions that maintain phase separation between the aqueous meduim and the extractant; and isolating the IFN-. beta. from the extractant such as by precipitating the IFN-. beta. from an aqeous buffer mixture of the extractant by lowering the pH thereof.

US Patent:

49593145, Sep 25, 1990

Filed:

Feb 7, 1985

Appl. No.:

6/698939

Inventors:

David F. Mark - Danville CA
Leo S. Lin - Fremont CA
Shi-da Yu Lu - Oakland CA
Alice M. Wang - Walnut Creek CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C12P 2100
C12P 1934
C12P 2122

US Classification:

435 691

Abstract:

Muteins of biologically active proteins such as IFN-. beta. 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.

US Patent:

46770631, Jun 30, 1987

Filed:

Jul 30, 1985

Appl. No.:

6/760661

Inventors:

David F. Mark - Danville CA
Alice M. Wang - Walnut Creek CA
Martha B. Ladner - Richmond CA
Abla A. Creasey - Piedmont CA
Leo S. Lin - Fremont CA
Janelle Van Arsdell - Richmond CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C12P 2100
C12N 1500
C12N 100
A61K 3900

US Classification:

435 68

Abstract:

Human tumor necrosis factor (TNF) has been prepared using recombinant methods. A human promyelocytic leukemia cell line has been induced using an improved induction procedure, and the TNF purified to homogeneity. Methods, vectors, and cells useful in obtaining human TNF in practical amounts are disclosed. Muteins having N-terminal deletions, which muteins have superior biological activity, are also disclosed.

US Patent:

46770640, Jun 30, 1987

Filed:

May 2, 1985

Appl. No.:

6/730696

Inventors:

David F. Mark - Danville CA
Alice M. Wang - Walnut Creek CA
Martha B. Ladner - Richmond CA
Abla A. Creasey - Piedmont CA
Janelle N. Van Arsdell - Richmond CA
Leo S. Lin - Fremont CA

Assignee:

Cetus Corporation - Emeryville CA

International Classification:

C12P 2100
C12N 1500
C12N 100
A61K 3900

US Classification:

435 68

Abstract:

Human Tumor necrosis factor (TNF) has been prepared using recombinant methods. A human promyelocytic leukemia cell line has been induced using an improved induction procedure, and the TNF purified to homogeneity. Methods, vectors, and cells useful in obtaining human TNF in practical amounts are disclosed. Muteins having N-terminal deletions, which muteins have superior biological activity, are also disclosed.