Lawrence J Forman

US Patent:

20040048368, Mar 11, 2004

Filed:

Aug 8, 2003

Appl. No.:

10/637918

Inventors:

Mary Chen - Burlingame CA, US
Lawrence Forman - Sunnyvale CA, US

Assignee:

Genentech, Inc. - South San Francisco CA

International Classification:

C12N005/02

US Classification:

435/325000, 435/383000

Abstract:

A method-of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1.0×10cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations. During the growth phase, production of potentially detrimental metabolic waste products, such as lactic acid, is controlled thereby curtailing the increase of osmolality due to accumulation and neutralization of waste products. Thus, the cell growth can be improved. In the production phase, the cell culture conditions are modified in order to arrest or reduce cell growth and thereby direct nutrient utilization toward production, as opposed to cell growth. Overall, it is intended that the method results in an improvement in specific productivity, reduction in production run times and/or an increase in final product concentration.

US Patent:

20050272124, Dec 8, 2005

Filed:

Jun 29, 2005

Appl. No.:

11/172090

Inventors:

Mary Chen - Burlingame CA, US
Lawrence Forman - Sunnyvale CA, US

Assignee:

Genentech, Inc. - South San Francisco CA

International Classification:

C12P021/06
C12N005/06

US Classification:

435069100, 435358000, 435320100

Abstract:

A method of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1.0×10cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations. During the growth phase, production of potentially detrimental metabolic waste products, such as lactic acid, is controlled thereby curtailing the increase of osmolality due to accumulation and neutralization of waste products. Thus, the cell growth can be improved. In the production phase, the cell culture conditions are modified in order to arrest or reduce cell growth and thereby direct nutrient utilization toward production, as opposed to cell growth. Overall, it is intended that the method results in an improvement in specific productivity, reduction in production run times and/or an increase in final product concentration.

US Patent:

61804010, Jan 30, 2001

Filed:

May 4, 1998

Appl. No.:

9/073198

Inventors:

Mary Chen - Burlingame CA
Lawrence W. Forman - Sunnyvale CA

Assignee:

Genentech, Inc. - South San Francisco CA

International Classification:

C12N 500
C12N 506

US Classification:

435358

Abstract:

A method of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0. 01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1. times. 10. sup. 6 cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0. 01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations.

US Patent:

58561790, Jan 5, 1999

Filed:

Mar 10, 1994

Appl. No.:

8/208888

Inventors:

Mary Chen - Burlingame CA
Lawrence W. Forman - Sunnyvale CA

Assignee:

Genentech, Inc. - South San Francisco CA

International Classification:

C12N 500
C12P 2106
C12P 2102
C12P 2104

US Classification:

435325

Abstract:

A method of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0. 01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1. times. 10. sup. 6 cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0. 01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations.

US Patent:

20220243192, Aug 4, 2022

Filed:

Apr 15, 2022

Appl. No.:

17/721930

Inventors:

- San Mateo CA, US
Lawrence Forman - San Mateo CA, US

Assignee:

CHO Plus, Inc. - San Mateo CA

International Classification:

C12N 15/10
C12N 5/16
C12N 15/02
C12N 5/071

Abstract:

This disclosure provides improved cell lines for manufacture of protein, considerably reducing the cost of commercial production. The cell lines are obtained by selecting cells from a mixed population for one or more characteristics that support protein production on a non-specific basis, such as the level of endoplasmic reticulum, Golgi apparatus, and/or other desired phenotypic features, compared with other cells in the starting mixture. Particularly effective producer cell lines can be obtained by preparing the cells for functional selection by making cell hybrids. A gene encoding a heterologous protein of interest may be transfected into the cells before or after one or more cycles of fusion and selection. Depending on the protein product being expressed, cell lines may be obtained that produce eight grams or more of protein per liter of culture fluid.

US Patent:

20220243193, Aug 4, 2022

Filed:

Apr 15, 2022

Appl. No.:

17/721995

Inventors:

- San Mateo CA, US
Lawrence Forman - San Mateo CA, US

Assignee:

CHO Plus, Inc. - San Mateo CA

International Classification:

C12N 15/10
C12N 5/16
C12N 15/02
C12N 5/071

Abstract:

This disclosure provides improved cell lines for manufacture of protein, considerably reducing the cost of commercial production. The cell lines are obtained by selecting cells from a mixed population for one or more characteristics that support cell growth, compared with other cells in the starting mixture. Particularly effective producer cell lines can be obtained by preparing the cells for functional selection by making cell hybrids. A gene encoding a therapeutic protein of interest may be transfected into the cells before or after one or more cycles of fusion and selection. Depending on the protein product being expressed, cell lines may be obtained that produce eight grams or more of protein per liter of culture fluid.

US Patent:

20190322999, Oct 24, 2019

Filed:

Jun 13, 2019

Appl. No.:

16/440776

Inventors:

- San Mateo CA, US
Lawrence Forman - San Mateo CA, US

Assignee:

CHO Plus, Inc. - San Mateo CA

International Classification:

C12N 15/10
C12N 5/071
C12N 15/02
C12N 5/16

Abstract:

This disclosure provides improved cell lines for manufacture of protein-based pharmaceutical agents, considerably reducing the cost of commercial production. The cell lines are obtained by selecting cells from a mixed population for one or more characteristics that support protein production on a non-specific basis, such as the level of endoplasmic reticulum, Golgi apparatus, and/or other desired phenotypic features, compared with other cells in the starting mixture. Particularly effective producer cell lines can be obtained by preparing the cells for functional selection by making cell hybrids. A gene encoding a therapeutic protein of interest may be transfected into the cells before or after one or more cycles of fusion and selection. Depending on the protein product being expressed, cell lines may be obtained that produce eight grams or more of protein per liter of culture fluid.