Engineering a Unique Conjugation Site on AB Light Chain

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$75,000.00
Award Year:
1994
Program:
SBIR
Phase:
Phase I
Contract:
1 R43 CA63984-1,
Award Id:
24875
Agency Tracking Number:
24875
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
300 American Road, Morris Plains, NJ, 07950
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Shui-On Leung
(201) 605-8200
Business Contact:
() -
Research Institution:
n/a
Abstract
Our objective is to establish that the naturally occurring asparagine- (Asn)- glycosylation sitefound in the light chain variable domain (VK) of a monoclonal antibody (MAb); LL2, is a potential site forthe universal conjugation of cytotoxic agents (e.g., doxorubicin) for cancer therapy. Phase I is focusedon confirming that the carbohydrate moiety found in the LL2 VK domain is a potential conjugation sitefor indirect dextran mediated drug attachment. LL2 fragment devoid of Fc carbohydrate will be usedas the substrate for conjugation. The effect of drug-dextran conjugation to the VK carbohydrate groupon the immunoreactivity of the antibody/fragment will also be evaluated. Meanwhile, Asn-glycosylationcorresponding to that in murine LL2 will be engineered, by oligonucleotide directed mutagenesis orpolymerase chain reaction (PCR), into the VK domains of humanized MN14 and/or LL2 antibody, in theoriginal sequence design of which no Asn-glycosylation site was incorporated. Expression vectors forthe humanized MN14 and/or LL2 containing the Asn-glycosylation site will be constructed and expressedin SP2/0 myeloma cells by transfection (electroporation). The efficiency of drug conjugation for theglycosylated humanized antibodies, either in the form of whole IgG or fragments, will be evaluated andcompared with that of their non-glycosylated counterparts.

* information listed above is at the time of submission.

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