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Antibody-Membrane Switch (AMS) technology for optimized antibody engineering

Award Number: R44AI109982
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2014
PERIOD OF PERFORMANCE END DATE: 05/31/2018

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Antibody-Membrane Switch (AMS) technology for optimized antibody engineering - ¿ DESCRIPTION (provided by applicant): Antibody-Membrane Switch (AMS) technology for optimized antibody engineering Abstract Generation of high-productivity cell lines remains a major bottleneck in therapeutic antibody development. Conventional cell line development depends on gene amplification methodologies using dihydrofolate reductase (DHFR) or glutamine synthetase (GS). Higher productivity is associated with an increased gene copy number. However, lack of selection pressure under the conditions of large scale manufacturing leads to clonal instability. We have developed a novel method for cell line development, Antibody Membrane Switch (AMS) technology that does not rely on gene amplification. This FACS-based, high-throughput method is facilitated by cell surface antibody expression to rapidly and efficiently isolate high producing cells. The switch between membrane expression and secretion is achieved by alternative splicing and specific DNA recombination. The antibody of interest is initially displayed on the cell surface to facilitate FACS. Isolated high producing cells are then seamlessly transformed into production cells after removing the membrane-anchoring domain sequence via a DNA recombinase. AMS technology has been applied in a number of antibody cell line development projects which typically last 2-3 months. The top manufacturing cell lines exhibit very high specific productivity of 40-60 pg./cell/day resulting in production titers of 2-4 g/L in 10-day batch culture. In Phase I studies the underlying AMS methods were reduce to practice. Furthermore, we have optimized the AMS process using two biosimilar antibodies. In Phase II, these optimized methods will be applied to screening of CHO surface displayed antibody libraries. An affinity maturation library and a naïve human antibody library will be constructed and utilized to screen by FACS for therapeutic antibody candidates. The screening will be carried out with soluble antigen for high affinity binding or antigen (e.g., GPCR) presenting cells for desired bio-activities. The isolated positive cells will be transformed into antibody production cells by DNA recombinase to remove the membrane anchorage. This successful application of AMS technology will permit the discovery of antibodies to be seamlessly linked to downstream cell line development providing the basis for rapid, facile cell line production directly from a novel antibody-discovery platform. Phase I: 1R43AI109982-01A1


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2016	PANORAMA RESEARCH	1230 BORDEAUX DR	SUNNYVALE	CA	94089	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	3	11/26/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $455,800 )
2016	2016	PANORAMA RESEARCH, INC	2462 WYANDOTTE STREET	MOUNTAIN VIEW	CA	94043	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	3	6/28/2016	NON-COMPETING CONTINUATION	$455,800
														Subtotal = $455,800

Issue Date FY: 2015 ( Subtotal = $499,789 )
2015	2015	PANORAMA RESEARCH, INC	2462 WYANDOTTE STREET	MOUNTAIN VIEW	CA	94043	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	2	6/15/2015	COMPETING CONTINUATION	$499,789
														Subtotal = $499,789

Grand Total All Awards = $955,589

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Antibody-Membrane Switch (AMS) technology for optimized antibody engineering

Award Number: R44AI109982

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2014

PERIOD OF PERFORMANCE END DATE: 05/31/2018

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