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Dock and Lock: novel protein engineering

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
79883
Program Year/Program:
2006 / SBIR
Agency Tracking Number:
CA123985
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
IMMUNOMEDICS, INC.
300 The American Road Morris Plains, NJ 07950-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2006
Title: Dock and Lock: novel protein engineering
Agency: HHS
Contract: 1R43CA123985-01
Award Amount: $134,285.00
 

Abstract:

DESCRIPTION (provided by applicant): The objective of this research is to develop a new generation of fusion proteins that can be used for improved imaging and therapy of cancer and other diseases by the method of pretargeting, which separates antibody localization from the delivery of diagnostic or therapeutic radionuclides. This application describes a novel technology for the facile and quantitative assembly of trivalent, bispecific, binding structures from two distinct fusion proteins, and proposes to advance prototype molecules composed of three Fab fragments that are stably linked and retain the binding affinity of the parental antibodies. These novel constructs were purified to homogeneity and shown to be useful for pretargeted delivery of radio-labeled tracers to human colonic tumor xenografts in nude mice, achieving exceptional tumor-to-nontumor ratios. For example, at 1 h post-injection of a 99mTc-labeled tracer, the tumor to blood ratio was as high as 66 q 5, with tumor uptake exceeding 30 % injected dose per gram. The primary aim of this application is to further characterize one such construct both in vitro and in vivo, so that the feasibility of its future clinical development for pretargeted therapy can be defined. Another key aim is to show that this new construct can be prepared more efficiently and with higher productivity than previously-generated recombinant bispecific antibodies from this group. Upon meeting these milestones, we should be in a position to submit a Phase II application directed toward additional development of this agent for initial clinical testing as pretargeted radioimmunotherapy of CEA-positive cancers, such as colonic cancer. This innovative research will produce multivalent, multifunctional, structures in general, and trivalent bispecific Fab-based binding proteins in particular, that can be useful for the detection, imaging, and therapy of various human diseases which have antigen targets, including cancers, cardiovascular diseases, autoimmune diseases, and infectious diseases.

Principal Investigator:

Chienhsing K. Chang
9736051330
kchang@immunomedics.com

Business Contact:

Phyllis Parker
9736058200
pparker@immunomedics.com
Small Business Information at Submission:

IMMUNOMEDICS, INC.
300 AMERICAN ROAD MORRIS PLAINS, NJ 07950

EIN/Tax ID: 611009366
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No